S-palmitoylation is one of the most common post-translational modifications in nature;however,its importance has been overlooked for decades.Crohn’s disease(CD),a subtype of inflammatory bowel disease(IBD),is an auto...S-palmitoylation is one of the most common post-translational modifications in nature;however,its importance has been overlooked for decades.Crohn’s disease(CD),a subtype of inflammatory bowel disease(IBD),is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract.Bowel damage and subsequent disabilities caused by CD are a growing global health issue.Well-acknowledged risk factors for CD include genetic susceptibility,environmental factors,such as a westernized lifestyle,and altered gut microbiota.However,the pathophysiological mechanisms of this disorder are not yet comprehensively understood.With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD,as recently reported,there is a need to investigate the relationship between CD and S-palmitoylation.In this review,we summarize the concept,detection,and function of S-palmitoylation as well as its potential effects on CD,and provide novel insights into the pathogenesis and treatment of CD.展开更多
Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
BACKGROUND Conventional Crohn’s disease(CD)treatments are supportive rather than curative and have serious side effects.Adipose-derived mesenchymal stem cells(ADSCs)have been gradually applied to treat various diseas...BACKGROUND Conventional Crohn’s disease(CD)treatments are supportive rather than curative and have serious side effects.Adipose-derived mesenchymal stem cells(ADSCs)have been gradually applied to treat various diseases.The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear.AIM To investigate the effect of ADSC administration on CD and explore the potential mechanisms.METHODS Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid(TNBS)to establish a rat model of CD,followed by tail injections of green fluorescent protein(GFP)-modified ADSCs.Flow cytometry,qRT-PCR,and Western blot were used to detect changes in the Wnt signaling pathway,T cell subtypes,and their related cytokines.RESULTS The isolated cells showed the characteristics of ADSCs,including spindle-shaped morphology,high expression of CD29,CD44,and CD90,low expression of CD34 and CD45,and osteogenic/adipogenic ability.ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD.Furthermore,serum anti-sacchromyces cerevisiae antibody and panti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSCtreated rats.Mechanistically,the GFP-ADSCs were colocalized with intestinal epithelial cells(IECs)in the CD rat model.GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression,decreased noncanonical Wnt signaling pathway expression,and increased apoptosis rates and protein level of cleaved caspase-3 in rats.In addition,ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production,disturbed T cell subtypes,and their related markers in rats.CONCLUSION Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation,the Wnt signaling pathway,and T cell immunity.展开更多
BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively p...BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.展开更多
BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-der...BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.展开更多
Eucommia ulmoides‘Hongye’is a new ornamental variety of E.ulmoides with excellent red or purple foliage.We found that E.ulmoides‘Hongye’exhibited a gradual change from green to red colour under light conditions.Ho...Eucommia ulmoides‘Hongye’is a new ornamental variety of E.ulmoides with excellent red or purple foliage.We found that E.ulmoides‘Hongye’exhibited a gradual change from green to red colour under light conditions.However,the colouring mechanism in the leaves of E.ulmoides‘Hongye’remains unclear.In this study,we compared the pigment content and leaf colour index of E.ulmoides‘Hongye’at five stages with those of E.ulmoides‘Xiaoye’,which was used as the control variety.The transcriptome sequencing data of the first-period(H1,green)and fifth-period(H5,red)leaves were also analysed and compared.The corresponding gene regulation in anthocyanin-related metabolic pathways was then analysed.Physiological results indicated that the contents of flavonoids and anthocyanins in red leaves(H5)were significantly higher than those in green leaves(H1),whereas the chlorophyll content in red leaves(H5)was lower than that in green leaves(H1).Moreover,the carotenoid content did not significantly differ between the two varieties.A transcriptome analysis identified 4240 differentially expressed genes(DEGs),and 20 of these genes were found to be involved in flavonoid and anthocyanin biosynthesis pathways.The results provide a reference for further study of the leaf colouration mechanism in E.ulmoides.展开更多
BACKGROUND Insomnia is the most common sleep disorder.It disrupts the patient’s life and work,increases the risk of various health issues,and often requires long-term intervention.The financial burden and inconvenien...BACKGROUND Insomnia is the most common sleep disorder.It disrupts the patient’s life and work,increases the risk of various health issues,and often requires long-term intervention.The financial burden and inconvenience of treatments discourage patients from complying with them,leading to chronic insomnia.AIM To investigate the long-term home-practice effects of mindful breathing combined with a sleep-inducing exercise as adjunctive insomnia therapy.METHODS A quasi-experimental design was used in the present work,in which the patients with insomnia were included and grouped based on hospital admission:40 patients admitted between January and April 2020 were assigned to the control group,and 40 patients admitted between May and August 2020 were assigned to the treatment group.The control group received routine pharmacological and physical therapies,while the treatment group received instruction in mindful breathing and a sleep-inducing exercise in addition to the routine therapies.The Pittsburgh Sleep Quality Index(PSQI),Generalized Anxiety Disorder 7-item(GAD-7)scale,and Insomnia Severity Index(ISI)were utilized to assess sleepquality improvement in the patient groups before the intervention and at 1 wk,1 mo,and 3 mo postintervention.RESULTS The PSQI,GAD-7,and ISI scores before the intervention and at 1 wk postintervention were not significantly different between the groups.However,compared with the control group,the treatment group exhibited significant improvements in sleep quality,daytime functioning,negative emotions,sleep latency,sleep duration,sleep efficiency,anxiety level,and insomnia severity at 1 and 3 mo postintervention(P<0.05).The results showed that mindful breathing combined with the sleep-inducing exercise significantly improved the long-term effectiveness of insomnia treatment.At 3 mo,the PSQI scores for the treatment vs the control group were as follows:Sleep quality 0.98±0.48 vs 1.60±0.63,sleep latency 1.98±0.53 vs 2.80±0.41,sleep duration 1.53±0.60 vs 2.70±0.56,sleep efficiency 2.35±0.58 vs 1.63±0.49,sleep disturbance 1.68±0.53 vs 2.35±0.53,hypnotic medication 0.53±0.64 vs 0.93±0.80,and daytime dysfunction 1.43±0.50 vs 2.48±0.51(all P<0.05).The GAD-7 scores were 2.75±1.50 vs 7.15±2.28,and the ISI scores were 8.68±2.26 vs 3.38±1.76 for the treatment vs the control group,respectively(all P<0.05).CONCLUSION These simple,cost-effective,and easy-to-implement practices used in clinical or home settings could have profound significance for long-term insomnia treatment and merit wide adoption in clinical practice.展开更多
Dear Editor,I am Dr. Tie-zhu Lin, from He Eye Specialist Hospital, Shenyang, China. I write to present the case of persistent macular oedema following Best vitelliform macular dystrophy(BVMD) undergoing anti-vascular ...Dear Editor,I am Dr. Tie-zhu Lin, from He Eye Specialist Hospital, Shenyang, China. I write to present the case of persistent macular oedema following Best vitelliform macular dystrophy(BVMD) undergoing anti-vascular endothelial growth factor(VEGF) treatment. BVMD also called Best’s disease, is a hereditary disease due to mutation in the BEST1 gene located on chromosome 11;and has vastly variable phenotypic expression.展开更多
The considerable hazard posed by periprosthetic joint infections underlines the urgent need for the rapid advancement of in-situ drug delivery systems within joint materials.However,the pursuit of sustained antibacter...The considerable hazard posed by periprosthetic joint infections underlines the urgent need for the rapid advancement of in-situ drug delivery systems within joint materials.However,the pursuit of sustained antibacterial efficacy remains a formidable challenge.In this context,we proposed a novel strategy that leverages swelling and erosion mechanisms to facilitate drug release of drug-loaded ultrahigh molecular weight polyethylene(UHMWPE),thereby ensuring its long-lasting antibacterial performance.Polyethylene oxide(PEO),a hydrophilic polymer with fast hydrating ability and high swelling capacity,was incorporated in UHMWPE alongside the antibacterial tea polyphenol(epigallocatechin gallate,EGCG as representative).The swelling of PEO enhanced water infiltration into the matrix,while the erosion of PEO balanced the release of the encapsulated EGCG,resulting in a steady release.The behavior was supported by the EGCG release profiles and the corresponding fitted release kinetic models.As demonstrated by segmented antibacterial assessments,the antibacterial efficiency was enhanced 2to 3 times in the PEO/EGCG/UHMWPE composite compared to that of EGCG/UHMWPE.Additionally,the PEO/EGCG/UHMWPE composite exhibited favorable biocompatibility and mechanical performance,making it a potential candidate for the development of drug-releasing joint implants to combat prosthetic bacterial infections.展开更多
RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identificati...RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.展开更多
To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans（PCDD/Fs） on the environment in the vicinity of municipal solid waste incinerators（MSWIs）, we determined the levels of ...To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans（PCDD/Fs） on the environment in the vicinity of municipal solid waste incinerators（MSWIs）, we determined the levels of PCDD/Fs in air and soil samples collected around a MSWI, which is the largest in China. The International Toxicity Equivalency Quantity（I-TEQ） concentrations of PCDD/Fs in air samples were from 0.0300 to 1.03 pg I-TEQ/m^3（0.445–13.6 pg/m^3）, with an average of 0.237 pg I-TEQ/m^3, while in soil samples they ranged from 0.520 to 3.40 pg I-TEQ/g（2.41–88.7 pg/g） with an average of1.49 pg I-TEQ/g. The concentrations of PCDD/Fs in air and soil samples were comparable to other areas, and Pe CDFs were the dominant contributors, which was different from stack gas homologue patterns. Multivariate statistical analysis showed that PCDD/Fs emission from the MSWI did not directly affect the profiles of PCDD/Fs in air and soils, so that vehicles and unidentified emission sources should be considered. The daily inhalation levels of PCDD/Fs for children（0.0110 to 0.392 pg I-TEQ/（kg·day） and adults（0.00600 to 0.221 pg I-TEQ/（kg·day） near the MSWI were lower than the tolerable daily intake of 1.00 to 4.00 pg WHO-TEQ/（kg·day）, but in winter the values were higher than in summer. These results can be used as basic data for assessing the risk of PCDD/Fs exposure in residents living around this MSWI, and more monitoring programs and studies should be carried out around MSWIs.展开更多
Traditional high strength engineering alloys suffer from serious surface brittleness and inferior wear performance when servicing under sliding contact at cryogenic temperature.Here,we report that the recently emergin...Traditional high strength engineering alloys suffer from serious surface brittleness and inferior wear performance when servicing under sliding contact at cryogenic temperature.Here,we report that the recently emerging CoCrNi multi-principal element alloy defies this trend and presents dramatically enhanced wear resistance when temperature decreases from 273 to 153 K,surpassing those of cryogenic austenitic steels.The temperature-dependent structure characteristics and deformation mechanisms influencing the cryogenic wear resistance of CoCrNi are clarified through microscopic observation and atomistic simulation.It is found that sliding-induced subsurface structures show distinct scenarios at different deformation temperatures.At cryogenic condition,significant grain refinement and a deep plastic zone give rise to an extended microstructural gradient below the surface,which can accommodate massive sliding deformation,in direct contrast to the strain localization and delamination at 273 K.Meanwhile,the temperature-dependent cryogenic deformation mechanisms(stacking fault networks and phase transformation)also provide additional strengthening and toughening of the subsurface material.These features make the CoCrNi alloy particularly wear resistant at cryogenic conditions and an excellent candidate for safety–critical applications.展开更多
Although various routes have been reported for haloazidation,unavoidable problems exist,such as environmentally unfriendly monomer halogen,the need for in situ generation of unstable halogen azides(XN3),applicability ...Although various routes have been reported for haloazidation,unavoidable problems exist,such as environmentally unfriendly monomer halogen,the need for in situ generation of unstable halogen azides(XN3),applicability to one type of haloazidation and inability to precisely control selectivity.Herein,we developed a universal strategy for haloazidation of alkenes through controlling the reactivity of IBA-N_(3) by switching halogen salts,allowing for the synthesis of a diversity of halogen azide products.Mechanistic studies have shown that by tuning the reactivity of IBA-N_(3) via switching halogen salts,different intermediates can be controllably produced to achieve regioselectivityand chemoselectivity in thehaloazidationof alkenes.展开更多
Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs in...Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs induced by cryogenic rejuvenation are still poorly understood.In the present study,nanoscopic wear tests were conducted on the Zr-based MGs surface with different CCT cycles using atomic force microscopy(AFM).After CCT treatment with 100 cycles,the MG displays the highest adhesion and ploughing frictions,but significantly improved anti-wear properties.Adhesion tests and molecular dynamics simulations disclose that the increased adhesion is attributed to the dominance of liquid-like regions in the CCT-treated MGs,and the impact of reduced hardness and weak elastic recovery results in the deteriorated ploughing friction.The enhanced plasticity effectively dissipates the strain from the AFM tip through multiple shear bands and weakens the adhesion during deformation,giving rise to excellent wear resistance.This study elucidates the promoting effect of CCT on the outstanding antiwear performance of MGs,and is helpful for the development of novel alloys.展开更多
Path-following control is one of the key technologies of autonomous vehicles,but the complex coupling effects and system uncertainties of vehicles can degrade their control performance.Accordingly,this study proposes ...Path-following control is one of the key technologies of autonomous vehicles,but the complex coupling effects and system uncertainties of vehicles can degrade their control performance.Accordingly,this study proposes targeted methods to solve different types of coupling in vehicle dynamics.First,the types of coupling are figured out and different handling strategies are proposed for each type,among which the coupling caused by steering angle,unsaturated tire forces,and load transfer can be treated as uncertainties in a unified form,such that the coupling effects can be treated in a decoupling way.Then,robust control methods for both lateral and longitudinal dynamics are proposed to deal with the uncertainties in dynamic and physical parameters.In lateral control,a robust feedback-feedforward scheme is utilized in lateral control to deal with such uncertainties.In longitudinal control,a radial basis function neural network-based adaptive sliding mode controller is introduced to deal with uncertainties and disturbances.In addition,the tire saturation coupling that cannot be handled by controllers is treated by a proposed speed profile.Simulation results based on the CarSim-Simulink joint platform evaluate the effectiveness and robustness of the proposed control method.The results show that compared with a well-designed robust controller,the velocity tracking performance,lateral tracking performance,and heading tracking performance improve by 55.68%,34.26%,and 52.41%,respectively,in the double-lane change maneuver,and increase by 87.79%,30.18%,and 9.68%,respectively,in the ramp maneuver.展开更多
Seasonal hibernation has provided an opportunity to study animals’phenotypic plasticity in adaptation to changing environment.In the present study focusing on the female Daurian ground squirrel(Spermophilus dauricus)...Seasonal hibernation has provided an opportunity to study animals’phenotypic plasticity in adaptation to changing environment.In the present study focusing on the female Daurian ground squirrel(Spermophilus dauricus)-a well demonstrated seasonal hibernator-we examined their behavioral,morphological,and metabolic changes during fattening,hibernation,and emergence.Our data indicated high levels of food intake,fat deposition,and body mass increases during fattening compared to hibernation.The levels of serum glucose and triglycerides were also higher during fattening than during hibernation and emergence.Interestingly,although squirrels showed signs of obesity and elevated triglycerides in serum during fattening,triglyceride levels in the liver and skeletal muscles remained unchanged.Our data also indicated that adiponectin levels in serum and cerebrospinal fluid were different between fattening and hibernation.Levels of adiponectin receptor 1 in the skeletal muscle remained low during fattening but peaked in late hibernation.In contrast,adiponectin receptor 2 in the liver showed a steady increase during fattening,which was followed by a significant decrease at early hibernation.Our data indicate that adiponectin may play an important role in preventing heterotopic fat accumulation in a receptor-and organ-specific manner,as well as in facilitating the switch from glucose metabolism to lipid metabolism during fattening and hibernation in female Daurian ground squirrels.展开更多
基金National Science Foundation of China,No.81770574Zhejiang Provincial National Science Foundation,No.LZ21H030002.
文摘S-palmitoylation is one of the most common post-translational modifications in nature;however,its importance has been overlooked for decades.Crohn’s disease(CD),a subtype of inflammatory bowel disease(IBD),is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract.Bowel damage and subsequent disabilities caused by CD are a growing global health issue.Well-acknowledged risk factors for CD include genetic susceptibility,environmental factors,such as a westernized lifestyle,and altered gut microbiota.However,the pathophysiological mechanisms of this disorder are not yet comprehensively understood.With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD,as recently reported,there is a need to investigate the relationship between CD and S-palmitoylation.In this review,we summarize the concept,detection,and function of S-palmitoylation as well as its potential effects on CD,and provide novel insights into the pathogenesis and treatment of CD.
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
基金National Natural Science Foundation of China,No.81770574,No.81600414,and No.81600447.
文摘BACKGROUND Conventional Crohn’s disease(CD)treatments are supportive rather than curative and have serious side effects.Adipose-derived mesenchymal stem cells(ADSCs)have been gradually applied to treat various diseases.The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear.AIM To investigate the effect of ADSC administration on CD and explore the potential mechanisms.METHODS Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid(TNBS)to establish a rat model of CD,followed by tail injections of green fluorescent protein(GFP)-modified ADSCs.Flow cytometry,qRT-PCR,and Western blot were used to detect changes in the Wnt signaling pathway,T cell subtypes,and their related cytokines.RESULTS The isolated cells showed the characteristics of ADSCs,including spindle-shaped morphology,high expression of CD29,CD44,and CD90,low expression of CD34 and CD45,and osteogenic/adipogenic ability.ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD.Furthermore,serum anti-sacchromyces cerevisiae antibody and panti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSCtreated rats.Mechanistically,the GFP-ADSCs were colocalized with intestinal epithelial cells(IECs)in the CD rat model.GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression,decreased noncanonical Wnt signaling pathway expression,and increased apoptosis rates and protein level of cleaved caspase-3 in rats.In addition,ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production,disturbed T cell subtypes,and their related markers in rats.CONCLUSION Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation,the Wnt signaling pathway,and T cell immunity.
基金the Natural Science Foundation of Zhejiang Province,No.LZ21H030002。
文摘BACKGROUND Obesity plays a vital role in the occurrence and development of non-alcoholic steatohepatitis(NASH).However,the underlining mechanism is still unclear,where adipose tissue(AT)derived exosomes may actively participate.MicroRNAs(miRNAs)are commonly secreted from exosomes for cell communication.Though the regulation of miR-103 on insulin sensitivity has been reported,the specific role of AT-derived exosomes miR-103 in NASH is still vague and further investigation may provide novel therapeutic choices.AIM To determine the specific role of AT-derived exosomes miR-103 in developing NASH through various methods.METHODS The expression levels of miR-103 in the AT-derived exosomes and livers were detected and compared between NASH mice and control.The effect of miR-103 on NASH progression was also explored by antagonizing miR-103,including steatosis and inflammation degree changes.The interaction between miR-103 and the autophagy-related gene phosphatase and tensin homolog(PTEN)was confirmed by dual-luciferase reporter assay.The role of the interaction between miR-103 and PTEN on autophagy was verified in NASH-like cells.Finally,the effects of miR-103 from adipose-derived exosomes on NASH and autophagy were analyzed through animal experiments.RESULTS The expression of miR-103 was increased in NASH mice,compared to the control,and inhibition of miR-103 could alleviate NASH.The results of the dual-luciferase reporter assay showed miR-103 could interact with PTEN.MiR-103-anta decreased p-AMPKa,p-mammalian target of rapamycin(mTOR),and p62 but increased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in NASH mice.Similar results were also observed in NASH-like cells,and further experiments showed PTEN silencing inhibited the effect of miR-103-anta.AT derivedexosome miR-103 aggravated NASH and increased the expressions of p-AMPKa,p-mTOR,and p62 but decreased the protein levels of PTEN and LC3-II/I and the number of autophagosomes in mice.CONCLUSION AT derived-exosome increased the levels of miR-103 in the liver,and miR-103 aggravated NASH.Mechanically,miR-103 could interact with PTEN and inhibit autophagy.
基金Supported by the National Natural Science Foundation of China,No.81770574the Natural Science Foundation of Zhejiang Province,No.LZ21H030002 and No.LY21H030005.
文摘BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.
基金Natural Science Foundation of Henan Province of China(202300410554)Key R&D and Promotion Project of Henan Province(Science and Technology Research)(192102110169,202102110229)].
文摘Eucommia ulmoides‘Hongye’is a new ornamental variety of E.ulmoides with excellent red or purple foliage.We found that E.ulmoides‘Hongye’exhibited a gradual change from green to red colour under light conditions.However,the colouring mechanism in the leaves of E.ulmoides‘Hongye’remains unclear.In this study,we compared the pigment content and leaf colour index of E.ulmoides‘Hongye’at five stages with those of E.ulmoides‘Xiaoye’,which was used as the control variety.The transcriptome sequencing data of the first-period(H1,green)and fifth-period(H5,red)leaves were also analysed and compared.The corresponding gene regulation in anthocyanin-related metabolic pathways was then analysed.Physiological results indicated that the contents of flavonoids and anthocyanins in red leaves(H5)were significantly higher than those in green leaves(H1),whereas the chlorophyll content in red leaves(H5)was lower than that in green leaves(H1).Moreover,the carotenoid content did not significantly differ between the two varieties.A transcriptome analysis identified 4240 differentially expressed genes(DEGs),and 20 of these genes were found to be involved in flavonoid and anthocyanin biosynthesis pathways.The results provide a reference for further study of the leaf colouration mechanism in E.ulmoides.
基金the Shengjing Hospital of China Medical University(approval No 2019PS582K).
文摘BACKGROUND Insomnia is the most common sleep disorder.It disrupts the patient’s life and work,increases the risk of various health issues,and often requires long-term intervention.The financial burden and inconvenience of treatments discourage patients from complying with them,leading to chronic insomnia.AIM To investigate the long-term home-practice effects of mindful breathing combined with a sleep-inducing exercise as adjunctive insomnia therapy.METHODS A quasi-experimental design was used in the present work,in which the patients with insomnia were included and grouped based on hospital admission:40 patients admitted between January and April 2020 were assigned to the control group,and 40 patients admitted between May and August 2020 were assigned to the treatment group.The control group received routine pharmacological and physical therapies,while the treatment group received instruction in mindful breathing and a sleep-inducing exercise in addition to the routine therapies.The Pittsburgh Sleep Quality Index(PSQI),Generalized Anxiety Disorder 7-item(GAD-7)scale,and Insomnia Severity Index(ISI)were utilized to assess sleepquality improvement in the patient groups before the intervention and at 1 wk,1 mo,and 3 mo postintervention.RESULTS The PSQI,GAD-7,and ISI scores before the intervention and at 1 wk postintervention were not significantly different between the groups.However,compared with the control group,the treatment group exhibited significant improvements in sleep quality,daytime functioning,negative emotions,sleep latency,sleep duration,sleep efficiency,anxiety level,and insomnia severity at 1 and 3 mo postintervention(P<0.05).The results showed that mindful breathing combined with the sleep-inducing exercise significantly improved the long-term effectiveness of insomnia treatment.At 3 mo,the PSQI scores for the treatment vs the control group were as follows:Sleep quality 0.98±0.48 vs 1.60±0.63,sleep latency 1.98±0.53 vs 2.80±0.41,sleep duration 1.53±0.60 vs 2.70±0.56,sleep efficiency 2.35±0.58 vs 1.63±0.49,sleep disturbance 1.68±0.53 vs 2.35±0.53,hypnotic medication 0.53±0.64 vs 0.93±0.80,and daytime dysfunction 1.43±0.50 vs 2.48±0.51(all P<0.05).The GAD-7 scores were 2.75±1.50 vs 7.15±2.28,and the ISI scores were 8.68±2.26 vs 3.38±1.76 for the treatment vs the control group,respectively(all P<0.05).CONCLUSION These simple,cost-effective,and easy-to-implement practices used in clinical or home settings could have profound significance for long-term insomnia treatment and merit wide adoption in clinical practice.
基金Natural Science Foundation of Liaoning Province,China (No.2020-MS-360)Shenyang Science and Technology Bureau (No.20-205-4-063)。
文摘Dear Editor,I am Dr. Tie-zhu Lin, from He Eye Specialist Hospital, Shenyang, China. I write to present the case of persistent macular oedema following Best vitelliform macular dystrophy(BVMD) undergoing anti-vascular endothelial growth factor(VEGF) treatment. BVMD also called Best’s disease, is a hereditary disease due to mutation in the BEST1 gene located on chromosome 11;and has vastly variable phenotypic expression.
基金the National Natural Science Foundation of China(No.5220031085)the Postdoctoral Research Project in Henan Province(No.HN2022054)+2 种基金the Key Scientific Research Projects of Colleges and Universities in Henan Province(No.23A430009)the State Key Laboratory of Polymer Materials Engineering(No.sklpme2022-4-03)the Key Technologies R&D Program of Henan Province(No.242102230131)。
文摘The considerable hazard posed by periprosthetic joint infections underlines the urgent need for the rapid advancement of in-situ drug delivery systems within joint materials.However,the pursuit of sustained antibacterial efficacy remains a formidable challenge.In this context,we proposed a novel strategy that leverages swelling and erosion mechanisms to facilitate drug release of drug-loaded ultrahigh molecular weight polyethylene(UHMWPE),thereby ensuring its long-lasting antibacterial performance.Polyethylene oxide(PEO),a hydrophilic polymer with fast hydrating ability and high swelling capacity,was incorporated in UHMWPE alongside the antibacterial tea polyphenol(epigallocatechin gallate,EGCG as representative).The swelling of PEO enhanced water infiltration into the matrix,while the erosion of PEO balanced the release of the encapsulated EGCG,resulting in a steady release.The behavior was supported by the EGCG release profiles and the corresponding fitted release kinetic models.As demonstrated by segmented antibacterial assessments,the antibacterial efficiency was enhanced 2to 3 times in the PEO/EGCG/UHMWPE composite compared to that of EGCG/UHMWPE.Additionally,the PEO/EGCG/UHMWPE composite exhibited favorable biocompatibility and mechanical performance,making it a potential candidate for the development of drug-releasing joint implants to combat prosthetic bacterial infections.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0801800,2021YFA1102400,2019YFA0802600 and 2021YFA0805703)the National Natural Science Foundation of China(81530007,31900072,31725013,82022001,82122005,81970103 and 81970101)CAMS Innovation Fund for Medical Sciences[2021-I2M-1-019 and 2021-I2M-1-040].
文摘RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.
基金supported by a special grant from the State Environmental Protection Administration, research and public service industry (Grant No. 201309029)
文摘To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans（PCDD/Fs） on the environment in the vicinity of municipal solid waste incinerators（MSWIs）, we determined the levels of PCDD/Fs in air and soil samples collected around a MSWI, which is the largest in China. The International Toxicity Equivalency Quantity（I-TEQ） concentrations of PCDD/Fs in air samples were from 0.0300 to 1.03 pg I-TEQ/m^3（0.445–13.6 pg/m^3）, with an average of 0.237 pg I-TEQ/m^3, while in soil samples they ranged from 0.520 to 3.40 pg I-TEQ/g（2.41–88.7 pg/g） with an average of1.49 pg I-TEQ/g. The concentrations of PCDD/Fs in air and soil samples were comparable to other areas, and Pe CDFs were the dominant contributors, which was different from stack gas homologue patterns. Multivariate statistical analysis showed that PCDD/Fs emission from the MSWI did not directly affect the profiles of PCDD/Fs in air and soils, so that vehicles and unidentified emission sources should be considered. The daily inhalation levels of PCDD/Fs for children（0.0110 to 0.392 pg I-TEQ/（kg·day） and adults（0.00600 to 0.221 pg I-TEQ/（kg·day） near the MSWI were lower than the tolerable daily intake of 1.00 to 4.00 pg WHO-TEQ/（kg·day）, but in winter the values were higher than in summer. These results can be used as basic data for assessing the risk of PCDD/Fs exposure in residents living around this MSWI, and more monitoring programs and studies should be carried out around MSWIs.
基金supported by the National Natural Science Foundation of China(52175188 and 51975474)National Key R&D Program of China(2022YFB3705300)+3 种基金Key Research and Development Program of Shaanxi Province(2023-YBGY-434)the Fundamental Research Funds for the Central Universities(3102019JC001)Open Fund of Liaoning Provincial Key Laboratory of Aero-engine Materials Tribology(LKLAMTF202301)C.G.acknowledges funding by the German Research Foundation(DFG)under Project G.R.4174/5 and by the European Research Council(ERC)under Grant No.771237.
文摘Traditional high strength engineering alloys suffer from serious surface brittleness and inferior wear performance when servicing under sliding contact at cryogenic temperature.Here,we report that the recently emerging CoCrNi multi-principal element alloy defies this trend and presents dramatically enhanced wear resistance when temperature decreases from 273 to 153 K,surpassing those of cryogenic austenitic steels.The temperature-dependent structure characteristics and deformation mechanisms influencing the cryogenic wear resistance of CoCrNi are clarified through microscopic observation and atomistic simulation.It is found that sliding-induced subsurface structures show distinct scenarios at different deformation temperatures.At cryogenic condition,significant grain refinement and a deep plastic zone give rise to an extended microstructural gradient below the surface,which can accommodate massive sliding deformation,in direct contrast to the strain localization and delamination at 273 K.Meanwhile,the temperature-dependent cryogenic deformation mechanisms(stacking fault networks and phase transformation)also provide additional strengthening and toughening of the subsurface material.These features make the CoCrNi alloy particularly wear resistant at cryogenic conditions and an excellent candidate for safety–critical applications.
基金the National Natural Science Foundation of China(22101215)the Independent Research Foundation of Key Laboratory of Green and Precise Synthetic Chemistry and Applications in Huaibei Normal University,Ministry of Education(KLGPSCA202208)+4 种基金the University Top Talents Academic Funding Project of Anhui Province(gxbjzD2021097),the Natural Science Foundation of Educational Committee from Anhui Province and Huaibei Normal University(KJ2020A00452023ZK0782023ZK079)University Outstanding Young Talents Support Program of Anhui Province(2023AH030078)the Crosswise Tasks of Huaibei Normal University(22100280).
文摘Although various routes have been reported for haloazidation,unavoidable problems exist,such as environmentally unfriendly monomer halogen,the need for in situ generation of unstable halogen azides(XN3),applicability to one type of haloazidation and inability to precisely control selectivity.Herein,we developed a universal strategy for haloazidation of alkenes through controlling the reactivity of IBA-N_(3) by switching halogen salts,allowing for the synthesis of a diversity of halogen azide products.Mechanistic studies have shown that by tuning the reactivity of IBA-N_(3) via switching halogen salts,different intermediates can be controllably produced to achieve regioselectivityand chemoselectivity in thehaloazidationof alkenes.
基金supported by the National Natural Science Foundation of China(Grant Nos.52175188,and 52201087)the Key Research and Development Program of Shaanxi Province(Grant No.2023-YBGY-434)+3 种基金the Natural Science Foundation of Shaanxi Province(Grant No.2022JM-253)the Open Fund of Liaoning Provincial Key Laboratory of Aero-engine Materials Tribology(Grant No.LKLAMTF202301)the Science and Technology on Reactor System Design Technology Laboratorythe Fundamental Research Funds for the Central Universities。
文摘Optimized macroscopic tribological behavior can be anticipated in metallic glasses(MGs)by cryogenic cycling treatment(CCT),which is attributed to enhanced plasticity.However,the intrinsic friction mechanisms of MGs induced by cryogenic rejuvenation are still poorly understood.In the present study,nanoscopic wear tests were conducted on the Zr-based MGs surface with different CCT cycles using atomic force microscopy(AFM).After CCT treatment with 100 cycles,the MG displays the highest adhesion and ploughing frictions,but significantly improved anti-wear properties.Adhesion tests and molecular dynamics simulations disclose that the increased adhesion is attributed to the dominance of liquid-like regions in the CCT-treated MGs,and the impact of reduced hardness and weak elastic recovery results in the deteriorated ploughing friction.The enhanced plasticity effectively dissipates the strain from the AFM tip through multiple shear bands and weakens the adhesion during deformation,giving rise to excellent wear resistance.This study elucidates the promoting effect of CCT on the outstanding antiwear performance of MGs,and is helpful for the development of novel alloys.
基金This work was supported by the key research program of the Ministry of Science and Technology(2017YFB0102603-3)the National Nature Science Foundation of China(51875061)+2 种基金Chongqing Science and Technology Program Project Basic Science and Frontier Technology(cstc2018jcyjAX0630)China Scholarship Council(201906050066)Graduate Sicentific Research/Innovation Foundation of Chongqing(CYB19063).
文摘Path-following control is one of the key technologies of autonomous vehicles,but the complex coupling effects and system uncertainties of vehicles can degrade their control performance.Accordingly,this study proposes targeted methods to solve different types of coupling in vehicle dynamics.First,the types of coupling are figured out and different handling strategies are proposed for each type,among which the coupling caused by steering angle,unsaturated tire forces,and load transfer can be treated as uncertainties in a unified form,such that the coupling effects can be treated in a decoupling way.Then,robust control methods for both lateral and longitudinal dynamics are proposed to deal with the uncertainties in dynamic and physical parameters.In lateral control,a robust feedback-feedforward scheme is utilized in lateral control to deal with such uncertainties.In longitudinal control,a radial basis function neural network-based adaptive sliding mode controller is introduced to deal with uncertainties and disturbances.In addition,the tire saturation coupling that cannot be handled by controllers is treated by a proposed speed profile.Simulation results based on the CarSim-Simulink joint platform evaluate the effectiveness and robustness of the proposed control method.The results show that compared with a well-designed robust controller,the velocity tracking performance,lateral tracking performance,and heading tracking performance improve by 55.68%,34.26%,and 52.41%,respectively,in the double-lane change maneuver,and increase by 87.79%,30.18%,and 9.68%,respectively,in the ramp maneuver.
基金This work was financially supported by the National Natural Scientific Foundation of China(Grant No.31670425)National Key Research and Development Program of China(2016YFC0500707)Liaoning Province Science and Technology Plan Project(2017208001).
文摘Seasonal hibernation has provided an opportunity to study animals’phenotypic plasticity in adaptation to changing environment.In the present study focusing on the female Daurian ground squirrel(Spermophilus dauricus)-a well demonstrated seasonal hibernator-we examined their behavioral,morphological,and metabolic changes during fattening,hibernation,and emergence.Our data indicated high levels of food intake,fat deposition,and body mass increases during fattening compared to hibernation.The levels of serum glucose and triglycerides were also higher during fattening than during hibernation and emergence.Interestingly,although squirrels showed signs of obesity and elevated triglycerides in serum during fattening,triglyceride levels in the liver and skeletal muscles remained unchanged.Our data also indicated that adiponectin levels in serum and cerebrospinal fluid were different between fattening and hibernation.Levels of adiponectin receptor 1 in the skeletal muscle remained low during fattening but peaked in late hibernation.In contrast,adiponectin receptor 2 in the liver showed a steady increase during fattening,which was followed by a significant decrease at early hibernation.Our data indicate that adiponectin may play an important role in preventing heterotopic fat accumulation in a receptor-and organ-specific manner,as well as in facilitating the switch from glucose metabolism to lipid metabolism during fattening and hibernation in female Daurian ground squirrels.
