Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important a...Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important and scarce network resources such as bandwidth and processing power.There have been several reports of these control signaling turning into signaling storms halting network operations and causing the respective Telecom companies big financial losses.This paper draws its motivation from such real network disaster incidents attributed to signaling storms.In this paper,we present a thorough survey of the causes,of the signaling storm problems in 3GPP-based mobile broadband networks and discuss in detail their possible solutions and countermeasures.We provide relevant analytical models to help quantify the effect of the potential causes and benefits of their corresponding solutions.Another important contribution of this paper is the comparison of the possible causes and solutions/countermeasures,concerning their effect on several important network aspects such as architecture,additional signaling,fidelity,etc.,in the form of a table.This paper presents an update and an extension of our earlier conference publication.To our knowledge,no similar survey study exists on the subject.展开更多
Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a d...Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.展开更多
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,...Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.展开更多
The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an impo...The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.展开更多
The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enh...The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, en...Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.展开更多
Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d...Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Th...Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Therefore,there is a great need for effective drugs against dTGCT with minor side effects.The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling plays a central role in rheumatoid arthritis(RA),a disease with similar characteristics as dTGCT,but its function in dTGCT remains unknown.dTGCT fibroblast-like synoviocytes(FLS)and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT.Cell viability,cell death,inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D)and macrophages were investigated for the efficacy of the JAK inhibitors.Here,we found that similar to RA,JAK/STAT signaling was markedly activated in the dTGCT synovium.Of the 5 JAK inhibitors,peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and macrophages.The potency of peficitinib was much higher than pexidartinib,which is the only FDA-approved drug for dTGCT.Mechanistically,peficitinib inhibited tyrosine kinase 2(TYK2),a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages.In summary,we not only revealed JAK/STAT(especially TYK2)signaling as the major mechanism underlying dTGCT,but also identified peficitinib as a promising drug against dTGCT.展开更多
Low-frequency signals have been proven valuable in the fields of target detection and geological exploration.Nevertheless,the practical implementation of these signals is hindered by large antenna diameters,limiting t...Low-frequency signals have been proven valuable in the fields of target detection and geological exploration.Nevertheless,the practical implementation of these signals is hindered by large antenna diameters,limiting their potential applications.Therefore,it is imperative to study the creation of lowfrequency signals using antennas with suitable dimensions.In contrast to conventional mechanical antenna techniques,our study generates low-frequency signals in the spatial domain utilizing the principle of the Doppler effect.We also defines the antenna array architecture,the timing sequency,and the radiating element signal waveform,and provides experimental prototypes including 8/64 antennas based on earlier research.In the conducted experiments,121 MHz,40 MHz,and 10 kHz composite signals are generated by 156 MHz radiating element signals.The composite signal spectrum matches the simulations,proving our low-frequency signal generating method works.This holds significant implications for research on generating low-frequency signals with small-sized antennas.展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
In x-ray dark-field imaging using dual phase grating interferometer,multi-contrast signals are extracted from a set of acquired phase-stepping data by using the least-squares fitting algorithm.The extracted mean inten...In x-ray dark-field imaging using dual phase grating interferometer,multi-contrast signals are extracted from a set of acquired phase-stepping data by using the least-squares fitting algorithm.The extracted mean intensity,amplitude and visibility signals may be intrinsically biased.However,it is still unclear how large these biases are and how the data acquisition parameters influence the biases in the extracted signals.This work set out to address these questions.Analytical expressions of the biases of the extracted signals were theoretically derived by using a second-order Taylor series expansion.Extensive numerical simulations were performed to validate the theoretical results.It is illustrated that while the estimated mean intensity signal is always unbiased,the estimated amplitude and visibility signals are both positively biased.While the biases of the estimated amplitude signals are proportional to the inverse of the total number of phase steps,the biases of the estimated visibility signals are inversely proportional to the product of the total number of phase steps and the mean number of photons counted per phase step.Meanwhile,it is demonstrated that the dependence of the biases on the mean visibility is quite different from that of Talbot-Lau interferometer due to the difference in the intensity model.We expect that these results can be useful for data acquisition optimizations and interpretation of x-ray dark-field images.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiabl...Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiable matter(USM),a composition of highly active ingredients found in walnut oil,has demonstrated antioxidant effects.This study aims to explore the neuroprotective effects of USM on d-galactose-treated C57BL/6 mice and elucidate its underlying mechanism,which was validated in PC12 cells treated with d-galactose.The results of behavioral tests demonstrated that USM significantly improved cognitive deficits associated with aging.The morphological analysis demonstrated that USM effectively alleviated hippocampal neuronal damage,synaptic impairment,and mitochondrial dysfunction induced by d-galactose.Furthermore,USM significantly increases the antioxidant enzymes activity while reducing the malondialdehyde and reactive oxygen species levels.The results suggest that USM can mitigate age-related symptoms caused by d-galactose by activating the nuclear factor erythroid-2-related factor 2 signaling pathway,which enhances the expression of antioxidant enzymes,restore redox balance,and improves synaptic and mitochondrial functions.This has a positive on improving cognition and memory disorders in elderly mice.展开更多
The time-varying periodic variations in Global Navigation Satellite System(GNSS)stations affect the reliable time series analysis and appropriate geophysical interpretation.In this study,we apply the singular spectrum...The time-varying periodic variations in Global Navigation Satellite System(GNSS)stations affect the reliable time series analysis and appropriate geophysical interpretation.In this study,we apply the singular spectrum analysis(SSA)method to characterize and interpret the periodic patterns of GNSS deformations in China using multiple geodetic datasets.These include 23-year observations from the Crustal Movement Observation Network of China(CMONOC),displacements inferred from the Gravity Recovery and Climate Experiment(GRACE),and loadings derived from Geophysical models(GM).The results reveal that all CMONOC time series exhibit seasonal signals characterized by amplitude and phase modulations,and the SSA method outperforms the traditional least squares fitting(LSF)method in extracting and interpreting the time-varying seasonal signals from the original time series.The decrease in the root mean square(RMS)correlates well with the annual cycle variance estimated by the SSA method,and the average reduction in noise amplitudes is nearly twice as much for SSA filtered results compared with those from the LSF method.With SSA analysis,the time-varying seasonal signals for all the selected stations can be identified in the reconstructed components corresponding to the first ten eigenvalues.Moreover,both RMS reduction and correlation analysis imply the advantages of GRACE solutions in explaining the GNSS periodic variations,and the geophysical effects can account for 71%of the GNSS annual amplitudes,and the average RMS reduction is 15%.The SSA method has proved to be useful for investigating the GNSS timevarying seasonal signals.It could be applicable as an auxiliary tool in the improvement of nonlinear variations investigations.展开更多
We propose the Dantzig selector based on the l_(1-q)(1<q≤2)minimization model for the sparse signal recovery.First,we discuss some properties of l_(1-q)minimization model and give some useful inequalities.Then,we ...We propose the Dantzig selector based on the l_(1-q)(1<q≤2)minimization model for the sparse signal recovery.First,we discuss some properties of l_(1-q)minimization model and give some useful inequalities.Then,we give a sufficient condition based on the restricted isometry property for the stable recovery of signals.The l_(1-2)minimization model of Yin-Lou-He is extended to the l_(1-q)minimization model.展开更多
BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes criti...BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes critically modulates inflammation and contributes to the progression of diabetic nephropathy.Sodiumglucose cotransporter 2 inhibitors such as dapagliflozin,which are acclaimed for their efficacy in diabetes management,may influence macrophage polarization,thereby ameliorating diabetic nephropathy.This investigation delves into these mechanistic pathways,aiming to elucidate novel therapeutic strategies for diabetes.AIM To investigate the inhibitory effect of dapagliflozin on macrophage M1 polarization and apoptosis and to explore its mechanism of action.METHODS We established a murine model of type 2 diabetes mellitus and harvested peritoneal macrophages following treatment with dapagliflozin.Concurrently,the human monocyte cell line cells were used for in vitro studies.Macrophage viability was assessed in a cell counting kit 8 assay,whereas apoptosis was evaluated by Annexin V/propidium iodide staining.Protein expression was examined through western blotting,and the expression levels of macrophage M1 surface immunosorbent assay,and quantitative real-time polymerase chain reaction analyses.RESULTS Dapagliflozin attenuated M1 macrophage polarization and mitigated apoptosis in the abdominal macrophages of diabetic mice,evidenced by the downregulation of proapoptotic genes(Caspase 3),inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α,and IL-1β],and M1 surface markers(inducible nitric oxide synthase,and cluster of differentiation 86),as well as the upregulation of the antiapoptotic gene BCL2.Moreover,dapagliflozin suppressed the expression of proteins associated with the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway(PI3K,AKT,phosphorylated protein kinase B).These observations were corroborated in vitro,where we found that the modulatory effects of dapagliflozin were abrogated by 740Y-P,an activator of the PI3K/AKT signaling pathway.CONCLUSION Dapagliflozin attenuates the polarization of macrophages toward the M1 phenotype,thereby mitigating inflammation and promoting macrophage apoptosis.These effects are likely mediated through the inhibition of the PI3K/AKT signaling pathway.展开更多
The article discusses the use of pulse-width modulation signals to generate low-temperature atmospheric plasma in an inert gas environment.The results of studies of the energy consumption of a low-temperature plasma g...The article discusses the use of pulse-width modulation signals to generate low-temperature atmospheric plasma in an inert gas environment.The results of studies of the energy consumption of a low-temperature plasma generation system depending on the duty rate,as well as the pulse repetition rate,are presented.The operating modes of the system have been established,in which a minimum of energy consumption is achieved.The issues of evaluating the interaction of plasma with objects based on the analysis of changes in signal parameters in the high-voltage circuit of the generator are also considered.展开更多
基金the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2024-9/1).
文摘Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important and scarce network resources such as bandwidth and processing power.There have been several reports of these control signaling turning into signaling storms halting network operations and causing the respective Telecom companies big financial losses.This paper draws its motivation from such real network disaster incidents attributed to signaling storms.In this paper,we present a thorough survey of the causes,of the signaling storm problems in 3GPP-based mobile broadband networks and discuss in detail their possible solutions and countermeasures.We provide relevant analytical models to help quantify the effect of the potential causes and benefits of their corresponding solutions.Another important contribution of this paper is the comparison of the possible causes and solutions/countermeasures,concerning their effect on several important network aspects such as architecture,additional signaling,fidelity,etc.,in the form of a table.This paper presents an update and an extension of our earlier conference publication.To our knowledge,no similar survey study exists on the subject.
基金Supported by National Key Research and Development Program Project,No.2017YFC1700601Shaanxi Provincial Key Research and Development Program Project,No.2018SF-350Leading Talents in Scientific and Technological Innovation of the Shaanxi Province Special Support Plan,No.00518。
文摘Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
基金Supported by National Natural Science Foundation of China,No.82374323and Hunan Graduate Research Innovation Project,No.2023CX15.
文摘Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.
基金supported by the National Natural Science Foundation of China,No.82371444(to YZ)the Natural Science Foundation of Hubei Province,No.2022CFB216(to XC)the Key Research Project of Ministry of Science and Technology of China,No.2022ZD021160(to YZ)。
文摘The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.
基金supported by the National Natural Science Foundation of China,No.82003965the Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2024MS167(to LH)+2 种基金the Xinglin Scholar Program of Chengdu University of Traditional Chinese Medicine,No.QJRC2022033(to LH)the Improvement Plan for the'Xinglin Scholar'Scientific Research Talent Program at Chengdu University of Traditional Chinese Medicine,No.XKTD2023002(to LH)the 2023 National Project of the College Students'Innovation and Entrepreneurship Training Program at Chengdu University of Traditional Chinese Medicine,No.202310633028(to FD)。
文摘The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain axis.The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine systems.Conversely,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host interactions.This reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological diseases.The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological diseases.This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological diseases.Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders.This can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage forms.These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
文摘Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.
基金supported in part by the National Natural Science Foundation of China(Nos.32270555 and 32072954).
文摘Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
基金supported by grants from the National Key R&D Program of China(2021YFF0501401,2018YFA0800501)National Natural Science Foundation of China(82325004,92168114,82172447)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0047).
文摘Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Therefore,there is a great need for effective drugs against dTGCT with minor side effects.The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling plays a central role in rheumatoid arthritis(RA),a disease with similar characteristics as dTGCT,but its function in dTGCT remains unknown.dTGCT fibroblast-like synoviocytes(FLS)and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT.Cell viability,cell death,inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D)and macrophages were investigated for the efficacy of the JAK inhibitors.Here,we found that similar to RA,JAK/STAT signaling was markedly activated in the dTGCT synovium.Of the 5 JAK inhibitors,peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and macrophages.The potency of peficitinib was much higher than pexidartinib,which is the only FDA-approved drug for dTGCT.Mechanistically,peficitinib inhibited tyrosine kinase 2(TYK2),a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages.In summary,we not only revealed JAK/STAT(especially TYK2)signaling as the major mechanism underlying dTGCT,but also identified peficitinib as a promising drug against dTGCT.
基金Science and Technology Project of Aerospace Information Research Institute,Chinese Academy of Sciences(Y910340Z2F)Science and Technology Project of BBEF(E3E2010201)。
文摘Low-frequency signals have been proven valuable in the fields of target detection and geological exploration.Nevertheless,the practical implementation of these signals is hindered by large antenna diameters,limiting their potential applications.Therefore,it is imperative to study the creation of lowfrequency signals using antennas with suitable dimensions.In contrast to conventional mechanical antenna techniques,our study generates low-frequency signals in the spatial domain utilizing the principle of the Doppler effect.We also defines the antenna array architecture,the timing sequency,and the radiating element signal waveform,and provides experimental prototypes including 8/64 antennas based on earlier research.In the conducted experiments,121 MHz,40 MHz,and 10 kHz composite signals are generated by 156 MHz radiating element signals.The composite signal spectrum matches the simulations,proving our low-frequency signal generating method works.This holds significant implications for research on generating low-frequency signals with small-sized antennas.
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.U1532113,11475170,11905041)Anhui Provincial Natural Science Foundation(Grant No.2208085MA18)Fundamental Research Funds for the Central Universities(Grant No.JZ2022HGTB0244)。
文摘In x-ray dark-field imaging using dual phase grating interferometer,multi-contrast signals are extracted from a set of acquired phase-stepping data by using the least-squares fitting algorithm.The extracted mean intensity,amplitude and visibility signals may be intrinsically biased.However,it is still unclear how large these biases are and how the data acquisition parameters influence the biases in the extracted signals.This work set out to address these questions.Analytical expressions of the biases of the extracted signals were theoretically derived by using a second-order Taylor series expansion.Extensive numerical simulations were performed to validate the theoretical results.It is illustrated that while the estimated mean intensity signal is always unbiased,the estimated amplitude and visibility signals are both positively biased.While the biases of the estimated amplitude signals are proportional to the inverse of the total number of phase steps,the biases of the estimated visibility signals are inversely proportional to the product of the total number of phase steps and the mean number of photons counted per phase step.Meanwhile,it is demonstrated that the dependence of the biases on the mean visibility is quite different from that of Talbot-Lau interferometer due to the difference in the intensity model.We expect that these results can be useful for data acquisition optimizations and interpretation of x-ray dark-field images.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金supported by the National Key Research and Development Program(2022YFD1600402)Hebei Provincial Major Science and Technology Achievement Transformation Project(21287101Z)Hebei Provincial Innovation and Entrepreneurship Team Project(215A7102D)。
文摘Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiable matter(USM),a composition of highly active ingredients found in walnut oil,has demonstrated antioxidant effects.This study aims to explore the neuroprotective effects of USM on d-galactose-treated C57BL/6 mice and elucidate its underlying mechanism,which was validated in PC12 cells treated with d-galactose.The results of behavioral tests demonstrated that USM significantly improved cognitive deficits associated with aging.The morphological analysis demonstrated that USM effectively alleviated hippocampal neuronal damage,synaptic impairment,and mitochondrial dysfunction induced by d-galactose.Furthermore,USM significantly increases the antioxidant enzymes activity while reducing the malondialdehyde and reactive oxygen species levels.The results suggest that USM can mitigate age-related symptoms caused by d-galactose by activating the nuclear factor erythroid-2-related factor 2 signaling pathway,which enhances the expression of antioxidant enzymes,restore redox balance,and improves synaptic and mitochondrial functions.This has a positive on improving cognition and memory disorders in elderly mice.
基金supported by the National Natural Science Foundation of China(NO.42104028,42174030 and 42004017)the Open Fund of Hubei Luojia Laboratory(No.220100048 and 230100021)the Scientific Research Project of Hubei Provincial Department of Education,and Research Foundation of the Department of Natural Resources of Hunan Province(No.20230104CH)。
文摘The time-varying periodic variations in Global Navigation Satellite System(GNSS)stations affect the reliable time series analysis and appropriate geophysical interpretation.In this study,we apply the singular spectrum analysis(SSA)method to characterize and interpret the periodic patterns of GNSS deformations in China using multiple geodetic datasets.These include 23-year observations from the Crustal Movement Observation Network of China(CMONOC),displacements inferred from the Gravity Recovery and Climate Experiment(GRACE),and loadings derived from Geophysical models(GM).The results reveal that all CMONOC time series exhibit seasonal signals characterized by amplitude and phase modulations,and the SSA method outperforms the traditional least squares fitting(LSF)method in extracting and interpreting the time-varying seasonal signals from the original time series.The decrease in the root mean square(RMS)correlates well with the annual cycle variance estimated by the SSA method,and the average reduction in noise amplitudes is nearly twice as much for SSA filtered results compared with those from the LSF method.With SSA analysis,the time-varying seasonal signals for all the selected stations can be identified in the reconstructed components corresponding to the first ten eigenvalues.Moreover,both RMS reduction and correlation analysis imply the advantages of GRACE solutions in explaining the GNSS periodic variations,and the geophysical effects can account for 71%of the GNSS annual amplitudes,and the average RMS reduction is 15%.The SSA method has proved to be useful for investigating the GNSS timevarying seasonal signals.It could be applicable as an auxiliary tool in the improvement of nonlinear variations investigations.
基金supported by the National Natural Science Foundation of China“Variable exponential function spaces on variable anisotropic Euclidean spaces and their applications”(12261083),“Harmonic analysis on affine symmetric spaces”(12161083).
文摘We propose the Dantzig selector based on the l_(1-q)(1<q≤2)minimization model for the sparse signal recovery.First,we discuss some properties of l_(1-q)minimization model and give some useful inequalities.Then,we give a sufficient condition based on the restricted isometry property for the stable recovery of signals.The l_(1-2)minimization model of Yin-Lou-He is extended to the l_(1-q)minimization model.
基金Natural Science Foundation of Anhui Province,No.2208085MH216Major Natural Science and Technology Project of Bengbu Medical College,No.2020byfy004Scientific Research Program of Anhui Provincial Health Commission,No.AHWJ2023BAc10028.
文摘BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes critically modulates inflammation and contributes to the progression of diabetic nephropathy.Sodiumglucose cotransporter 2 inhibitors such as dapagliflozin,which are acclaimed for their efficacy in diabetes management,may influence macrophage polarization,thereby ameliorating diabetic nephropathy.This investigation delves into these mechanistic pathways,aiming to elucidate novel therapeutic strategies for diabetes.AIM To investigate the inhibitory effect of dapagliflozin on macrophage M1 polarization and apoptosis and to explore its mechanism of action.METHODS We established a murine model of type 2 diabetes mellitus and harvested peritoneal macrophages following treatment with dapagliflozin.Concurrently,the human monocyte cell line cells were used for in vitro studies.Macrophage viability was assessed in a cell counting kit 8 assay,whereas apoptosis was evaluated by Annexin V/propidium iodide staining.Protein expression was examined through western blotting,and the expression levels of macrophage M1 surface immunosorbent assay,and quantitative real-time polymerase chain reaction analyses.RESULTS Dapagliflozin attenuated M1 macrophage polarization and mitigated apoptosis in the abdominal macrophages of diabetic mice,evidenced by the downregulation of proapoptotic genes(Caspase 3),inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α,and IL-1β],and M1 surface markers(inducible nitric oxide synthase,and cluster of differentiation 86),as well as the upregulation of the antiapoptotic gene BCL2.Moreover,dapagliflozin suppressed the expression of proteins associated with the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway(PI3K,AKT,phosphorylated protein kinase B).These observations were corroborated in vitro,where we found that the modulatory effects of dapagliflozin were abrogated by 740Y-P,an activator of the PI3K/AKT signaling pathway.CONCLUSION Dapagliflozin attenuates the polarization of macrophages toward the M1 phenotype,thereby mitigating inflammation and promoting macrophage apoptosis.These effects are likely mediated through the inhibition of the PI3K/AKT signaling pathway.
文摘The article discusses the use of pulse-width modulation signals to generate low-temperature atmospheric plasma in an inert gas environment.The results of studies of the energy consumption of a low-temperature plasma generation system depending on the duty rate,as well as the pulse repetition rate,are presented.The operating modes of the system have been established,in which a minimum of energy consumption is achieved.The issues of evaluating the interaction of plasma with objects based on the analysis of changes in signal parameters in the high-voltage circuit of the generator are also considered.
