In the post-college era,university research organizations are facing unprecedented changes in their structure and operational models.In terms of organizational form,these institutions are transitioning from single-dis...In the post-college era,university research organizations are facing unprecedented changes in their structure and operational models.In terms of organizational form,these institutions are transitioning from single-disciplinebased models to interdisciplinary and multidisciplinary collaboration models.This shift reflects the growing need to address complex,real-world problems that require expertise from multiple fields.From a management perspective,interdisciplinary research organizations face unique challenges.They must coordinate researchers from diverse disciplinary backgrounds,navigate potential conflicts between traditional departments and interdisciplinary units,and address differences in goals and organizational culture among members.These complexities make management more intricate and demanding.Simultaneously,the focus of university research organizations has become increasingly interest-driven,with research objectives,content,and participants reflecting specific areas of interest or societal demand.To adapt to these evolving trends,university research organizations must adopt flexible models tailored to their unique development needs.This approach will ensure the efficient execution of research activities and facilitate the effective transformation of research outcomes into practical applications.展开更多
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed...The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.展开更多
Solvent extraction,a separation and purification technology,is crucial in critical metal metallurgy.Organic solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and ...Solvent extraction,a separation and purification technology,is crucial in critical metal metallurgy.Organic solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and flammability,causing a spectrum of hazards to human health and environmental safety.Neoteric solvents have been recognized as potential alternatives to these harmful organic solvents.In the past two decades,several neoteric solvents have been proposed,including ionic liquids(ILs)and deep eutectic solvents(DESs).DESs have gradually become the focus of green solvents owing to several advantages,namely,low toxicity,degradability,and low cost.In this critical review,their classification,formation mechanisms,preparation methods,characterization technologies,and special physicochemical properties based on the most recent advancements in research have been systematically described.Subsequently,the major separation and purification applications of DESs in critical metal metallurgy were comprehensively summarized.Finally,future opportunities and challenges of DESs were explored in the current research area.In conclusion,this review provides valuable insights for improving our overall understanding of DESs,and it holds important potential for expanding separation and purification applications in critical metal metallurgy.展开更多
The rapid development of short video platforms poses new challenges for traditional recommendation systems.Recommender systems typically depend on two types of user behavior feedback to construct user interest profile...The rapid development of short video platforms poses new challenges for traditional recommendation systems.Recommender systems typically depend on two types of user behavior feedback to construct user interest profiles:explicit feedback(interactive behavior),which significantly influences users’short-term interests,and implicit feedback(viewing time),which substantially affects their long-term interests.However,the previous model fails to distinguish between these two feedback methods,leading it to predict only the overall preferences of users based on extensive historical behavior sequences.Consequently,it cannot differentiate between users’long-term and shortterm interests,resulting in low accuracy in describing users’interest states and predicting the evolution of their interests.This paper introduces a video recommendationmodel calledCAT-MFRec(CrossAttention Transformer-Mixed Feedback Recommendation)designed to differentiate between explicit and implicit user feedback within the DIEN(Deep Interest Evolution Network)framework.This study emphasizes the separate learning of the two types of behavioral feedback,effectively integrating them through the cross-attention mechanism.Additionally,it leverages the long sequence dependence capabilities of Transformer technology to accurately construct user interest profiles and predict the evolution of user interests.Experimental results indicate that CAT-MF Rec significantly outperforms existing recommendation methods across various performance indicators.This advancement offers new theoretical and practical insights for the development of video recommendations,particularly in addressing complex and dynamic user behavior patterns.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Point defect engineering endows catalysts with novel physical and chemical properties,elevating their electrocatalytic efficiency.The introduction of defects emerges as a promising strategy,effectively modifying the e...Point defect engineering endows catalysts with novel physical and chemical properties,elevating their electrocatalytic efficiency.The introduction of defects emerges as a promising strategy,effectively modifying the electronic structure of active sites.This optimization influences the adsorption energy of intermediates,thereby mitigating reaction energy barriers,altering paths,enhancing selectivity,and ultimately improving the catalytic efficiency of electrocatalysts.To elucidate the impact of defects on the electrocatalytic process,we comprehensively outline the roles of various point defects,their synthetic methodologies,and characterization techniques.Importantly,we consolidate insights into the relationship between point defects and catalytic activity for hydrogen/oxygen evolution and CO_(2)/O_(2)/N_(2) reduction reactions by integrating mechanisms from diverse reactions.This underscores the pivotal role of point defects in enhancing catalytic performance.At last,the principal challenges and prospects associated with point defects in current electrocatalysts are proposed,emphasizing their role in advancing the efficiency of electrochemical energy storage and conversion materials.展开更多
The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of ...The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.展开更多
Renal anastomotic hemangioma(AH)is a rare,benign vascular tumor with unique histopathological features,a disease that is clinically rare,and existing clinical cases offer different treatment options.As reported in the...Renal anastomotic hemangioma(AH)is a rare,benign vascular tumor with unique histopathological features,a disease that is clinically rare,and existing clinical cases offer different treatment options.As reported in the text,this is a very unusual case of renal AH with AH secondary to residual renal tissue after renal clear cell carcinoma,describing a rare renal AH and a history of renal clear cell carcinoma,including ultrasound,computed tomography and magnetic re-sonance imaging.However,the available imaging data and the literature do not provide an effective basis for the diagnosis of the disease,raising the lack of un-derstanding and misdiagnosis,where the patient eventually underwent neph-rectomy,but the author is not the most appropriate surgical treatment.The po-stoperative pathological results of the patient are benign lesions,and it is unde-niable that nephrectomy is suspected to be overtreated.By reading the literature,we provide different insights into the treatment of the patient,and we hope that this paper can provide some help for the future clinical diagnosis and treatment.展开更多
We have described in detail the effects of nano-SiO_(2),nano-CaCO_(3),carbon nanotubes,and nano-Al_(2)O_(3) on geopolymer concrete from the perspectives of macro mechanics and microstructure.The existing research resu...We have described in detail the effects of nano-SiO_(2),nano-CaCO_(3),carbon nanotubes,and nano-Al_(2)O_(3) on geopolymer concrete from the perspectives of macro mechanics and microstructure.The existing research results show that the mechanism of nano-materials on geopolymer concrete mainly includes the filling effect,nucleation effect,and bridging effect,the appropriate amount of nano-materials can be used as fillers to reduce the porosity of geopolymer concrete,and can also react with Ca(OH)2 to produce C-S-H gel,thereby improving the mechanical properties of geopolymer concrete.The optimum content of nano-SiO_(2) is between 1.0%and 2.0%.The optimum content of nano-CaCO_(3) is between 2.0%and 3.0%.The optimum content of carbon nanotubes is between 0.1%and 0.2%.The optimum content of nano-Al_(2)O_(3) is between 1.0%and 2.0%.The main problems existing in the research and application of nanomaterial-modified geopolymer concrete are summarized,which lays a foundation for the further application of nanomaterial in geopolymer concrete.展开更多
Joint Multimodal Aspect-based Sentiment Analysis(JMASA)is a significant task in the research of multimodal fine-grained sentiment analysis,which combines two subtasks:Multimodal Aspect Term Extraction(MATE)and Multimo...Joint Multimodal Aspect-based Sentiment Analysis(JMASA)is a significant task in the research of multimodal fine-grained sentiment analysis,which combines two subtasks:Multimodal Aspect Term Extraction(MATE)and Multimodal Aspect-oriented Sentiment Classification(MASC).Currently,most existing models for JMASA only perform text and image feature encoding from a basic level,but often neglect the in-depth analysis of unimodal intrinsic features,which may lead to the low accuracy of aspect term extraction and the poor ability of sentiment prediction due to the insufficient learning of intra-modal features.Given this problem,we propose a Text-Image Feature Fine-grained Learning(TIFFL)model for JMASA.First,we construct an enhanced adjacency matrix of word dependencies and adopt graph convolutional network to learn the syntactic structure features for text,which addresses the context interference problem of identifying different aspect terms.Then,the adjective-noun pairs extracted from image are introduced to enable the semantic representation of visual features more intuitive,which addresses the ambiguous semantic extraction problem during image feature learning.Thereby,the model performance of aspect term extraction and sentiment polarity prediction can be further optimized and enhanced.Experiments on two Twitter benchmark datasets demonstrate that TIFFL achieves competitive results for JMASA,MATE and MASC,thus validating the effectiveness of our proposed methods.展开更多
BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for r...BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.AIM To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.METHODS Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were identified.Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.RESULTS Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.After treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia.Olanzapine effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.Ten core targets of olanzapine were involved in several key pathways.CONCLUSION The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.展开更多
Mixed matrix membranes(MMMs)have demonstrated significant promise in energy-intensive gas separations by amalgamating the unique properties of fillers with the facile processability of polymers.However,achieving a sim...Mixed matrix membranes(MMMs)have demonstrated significant promise in energy-intensive gas separations by amalgamating the unique properties of fillers with the facile processability of polymers.However,achieving a simultaneous enhancement of permeability and selectivity remains a formidable challenge,due to the difficulty of achieving an optimal match between polymers and fillers.In this study,we incorporate a porous carbon-based zinc oxide composite(C@ZnO)into high-permeability polymers of intrinsic microporosity(PIMs)to fabricate MMMs.The dipole–dipole interaction between C@ZnO and PIMs ensures their exceptional compatibility,mitigating the formation of non-selective voids in the resulting MMMs.Concurrently,C@ZnO with abundant interconnected pores can provide additional low-resistance pathways for gas transport in MMMs.As a result,the CO_(2) permeability of the optimized C@ZnO/PIM-1 MMMs is elevated to 13,215 barrer,while the CO_(2)/N_(2) and CO_(2)/CH_(4) selectivity reached 21.5 and 14.4,respectively,substantially surpassing the 2008 Robeson upper bound.Additionally,molecular simulation results further corroborate that the augmented membrane gas selectivity is attributed to the superior CO_(2) affinity of C@ZnO.In summary,we believe that this work not only expands the application of MMMs for gas separation but also heralds a paradigm shift in the application of porous carbon materials.展开更多
To investigate the evolution of load-bearing characteristics of pre-stressed beams throughout their service life and to provide a basis for accurately assessing the actual working state of damaged pre-stressed concret...To investigate the evolution of load-bearing characteristics of pre-stressed beams throughout their service life and to provide a basis for accurately assessing the actual working state of damaged pre-stressed concrete T-beams,destructive tests were conducted on full-scale pre-stressed concrete beams.Based on the measurement and ana-lysis of beam deflection,strain,and crack development under various loading levels during the research tests,combined with the verification coefficient indicators specified in the codes,the verification coefficients of bridges at different stages of damage can be examined.The results indicate that the T-beams experience complete,incom-plete linear,and non-linear stages during the destructive test process.In the complete linear elastic stage,both the deflection and bottom strain verification coefficients comply with the specifications,indicating a good structural load-bearing capacity no longer adheres to the code’s requirements.In the non-linear stage,both coefficients exhi-bit a sharp increase,resulting in a further decrease in the structure’s load-bearing capacity.According to the pro-visions of the current code,the beam can be in the incomplete linear stage when both values fall within the code’s specified range.The strain verification coefficient sourced from the compression zone at the bottom of theflange is not recommended for assessing the bridge’s load-bearing capacity.展开更多
Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
Flexible wearable optoelectronic devices fabricated fromorganic–inorganic hybrid perovskites significantly accelerate the developmentof portable energy,biomedicine,and sensing fields,but their poor thermal stabilityh...Flexible wearable optoelectronic devices fabricated fromorganic–inorganic hybrid perovskites significantly accelerate the developmentof portable energy,biomedicine,and sensing fields,but their poor thermal stabilityhinders further applications.Conversely,all-inorganic perovskites possessexcellent thermal stability,but black-phase all-inorganic perovskite filmusually requires high-temperature annealing steps,which increases energy consumptionand is not conducive to the fabrication of flexible wearable devices.In this work,an unprecedented low-temperature fabrication of stable blackphaseCsPbI3perovskite films is demonstrated by the in situ hydrolysis reactionof diphenylphosphinic chloride additive.The released diphenyl phosphateand chloride ions during the hydrolysis reaction significantly lower the phasetransition temperature and effectively passivate the defects in the perovskitefilms,yielding high-performance photodetectors with a responsivity of 42.1 AW−1 and a detectivity of 1.3×10^(14)Jones.Furthermore,high-fidelity imageand photoplethysmography sensors are demonstrated based on the fabricated flexible wearable photodetectors.This work provides a newperspective for the low-temperature fabrication of large-area all-inorganic perovskite flexible optoelectronic devices.展开更多
Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Curre...Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.展开更多
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
This study highlights the importance of identifying and addressing risk factors associated with wound complications following transtibial amputation in diabetic patients.These amputations,often necessitated by severe ...This study highlights the importance of identifying and addressing risk factors associated with wound complications following transtibial amputation in diabetic patients.These amputations,often necessitated by severe diabetic foot ulcers,carry significant risks of postoperative complications such as infection and delayed wound healing.Elevated hemoglobin A1c levels,indicative of poor glycemic control,and a history of kidney transplantation,due to required immunosuppressive therapy,are key factors influencing these outcomes.This paper emphasizes the need for enhanced glycemic management and personalized postoperative care,particularly for immunocompromised individuals,to minimize complications and improve patient prognosis.Future research should focus on prospective studies to validate targeted interventions and optimize care strategies,ultimately aiming to reduce the healthcare burden associated with diabetic foot complications.展开更多
This letter compares the clinical efficacy and economic feasibility of the scoliocorrector fatma-UI(SCFUI)with direct vertebral rotation(DVR)in treating adolescent idiopathic scoliosis(AIS).SCFUI has shown promising r...This letter compares the clinical efficacy and economic feasibility of the scoliocorrector fatma-UI(SCFUI)with direct vertebral rotation(DVR)in treating adolescent idiopathic scoliosis(AIS).SCFUI has shown promising results in threedimensional spinal correction,providing superior rotational alignment compared to DVR and achieving significant improvements in coronal and sagittal planes.Additionally,SCFUI’s advanced design reduces risks associated with AIS surgeries and enhances overall patient outcomes.Economic analysis reveals SCFUI as a cost-effective option,potentially lowering long-term healthcare costs by minimizing complications and revisions.Our findings suggest that SCFUI is a viable,innovative approach in AIS treatment,meeting clinical and economic demands in orthopedic care.展开更多
BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,b...BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.展开更多
文摘In the post-college era,university research organizations are facing unprecedented changes in their structure and operational models.In terms of organizational form,these institutions are transitioning from single-disciplinebased models to interdisciplinary and multidisciplinary collaboration models.This shift reflects the growing need to address complex,real-world problems that require expertise from multiple fields.From a management perspective,interdisciplinary research organizations face unique challenges.They must coordinate researchers from diverse disciplinary backgrounds,navigate potential conflicts between traditional departments and interdisciplinary units,and address differences in goals and organizational culture among members.These complexities make management more intricate and demanding.Simultaneously,the focus of university research organizations has become increasingly interest-driven,with research objectives,content,and participants reflecting specific areas of interest or societal demand.To adapt to these evolving trends,university research organizations must adopt flexible models tailored to their unique development needs.This approach will ensure the efficient execution of research activities and facilitate the effective transformation of research outcomes into practical applications.
基金supported by the National Natural Science Foundation of China,Nos.91849115 and U1904207(to YX),81974211 and 82171247(to CS)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2020-PT310-01(to YX).
文摘The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.
基金financially supported by the Original Exploration Project of the National Natural Science Foundation of China(No.52150079)the National Natural Science Foundation of China(Nos.U22A20130,U2004215,and 51974280)+1 种基金the Natural Science Foundation of Henan Province of China(No.232300421196)the Project of Zhongyuan Critical Metals Laboratory of China(Nos.GJJSGFYQ202304,GJJSGFJQ202306,GJJSGFYQ202323,GJJSGFYQ202308,and GJJSGFYQ202307)。
文摘Solvent extraction,a separation and purification technology,is crucial in critical metal metallurgy.Organic solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and flammability,causing a spectrum of hazards to human health and environmental safety.Neoteric solvents have been recognized as potential alternatives to these harmful organic solvents.In the past two decades,several neoteric solvents have been proposed,including ionic liquids(ILs)and deep eutectic solvents(DESs).DESs have gradually become the focus of green solvents owing to several advantages,namely,low toxicity,degradability,and low cost.In this critical review,their classification,formation mechanisms,preparation methods,characterization technologies,and special physicochemical properties based on the most recent advancements in research have been systematically described.Subsequently,the major separation and purification applications of DESs in critical metal metallurgy were comprehensively summarized.Finally,future opportunities and challenges of DESs were explored in the current research area.In conclusion,this review provides valuable insights for improving our overall understanding of DESs,and it holds important potential for expanding separation and purification applications in critical metal metallurgy.
基金supported by National Natural Science Foundation of China(62072416)Key Research and Development Special Project of Henan Province(221111210500)Key TechnologiesR&DProgram of Henan rovince(232102211053,242102211071).
文摘The rapid development of short video platforms poses new challenges for traditional recommendation systems.Recommender systems typically depend on two types of user behavior feedback to construct user interest profiles:explicit feedback(interactive behavior),which significantly influences users’short-term interests,and implicit feedback(viewing time),which substantially affects their long-term interests.However,the previous model fails to distinguish between these two feedback methods,leading it to predict only the overall preferences of users based on extensive historical behavior sequences.Consequently,it cannot differentiate between users’long-term and shortterm interests,resulting in low accuracy in describing users’interest states and predicting the evolution of their interests.This paper introduces a video recommendationmodel calledCAT-MFRec(CrossAttention Transformer-Mixed Feedback Recommendation)designed to differentiate between explicit and implicit user feedback within the DIEN(Deep Interest Evolution Network)framework.This study emphasizes the separate learning of the two types of behavioral feedback,effectively integrating them through the cross-attention mechanism.Additionally,it leverages the long sequence dependence capabilities of Transformer technology to accurately construct user interest profiles and predict the evolution of user interests.Experimental results indicate that CAT-MF Rec significantly outperforms existing recommendation methods across various performance indicators.This advancement offers new theoretical and practical insights for the development of video recommendations,particularly in addressing complex and dynamic user behavior patterns.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by the National Natural Science Foundation of China(U21A20281)the Special Fund for Young Teachers from Zhengzhou University(JC23557030,JC23257011)+1 种基金the Key Research Projects of Higher Education Institutions of Henan Province(24A530009)the Project of Zhongyuan Critical Metals Laboratory(GJJSGFYQ202336).
文摘Point defect engineering endows catalysts with novel physical and chemical properties,elevating their electrocatalytic efficiency.The introduction of defects emerges as a promising strategy,effectively modifying the electronic structure of active sites.This optimization influences the adsorption energy of intermediates,thereby mitigating reaction energy barriers,altering paths,enhancing selectivity,and ultimately improving the catalytic efficiency of electrocatalysts.To elucidate the impact of defects on the electrocatalytic process,we comprehensively outline the roles of various point defects,their synthetic methodologies,and characterization techniques.Importantly,we consolidate insights into the relationship between point defects and catalytic activity for hydrogen/oxygen evolution and CO_(2)/O_(2)/N_(2) reduction reactions by integrating mechanisms from diverse reactions.This underscores the pivotal role of point defects in enhancing catalytic performance.At last,the principal challenges and prospects associated with point defects in current electrocatalysts are proposed,emphasizing their role in advancing the efficiency of electrochemical energy storage and conversion materials.
基金Supported by The College Students’Innovation and Entrepreneurship Competition,No.2024cxcy504 and No.202410459164.
文摘The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.
文摘Renal anastomotic hemangioma(AH)is a rare,benign vascular tumor with unique histopathological features,a disease that is clinically rare,and existing clinical cases offer different treatment options.As reported in the text,this is a very unusual case of renal AH with AH secondary to residual renal tissue after renal clear cell carcinoma,describing a rare renal AH and a history of renal clear cell carcinoma,including ultrasound,computed tomography and magnetic re-sonance imaging.However,the available imaging data and the literature do not provide an effective basis for the diagnosis of the disease,raising the lack of un-derstanding and misdiagnosis,where the patient eventually underwent neph-rectomy,but the author is not the most appropriate surgical treatment.The po-stoperative pathological results of the patient are benign lesions,and it is unde-niable that nephrectomy is suspected to be overtreated.By reading the literature,we provide different insights into the treatment of the patient,and we hope that this paper can provide some help for the future clinical diagnosis and treatment.
基金Funded by the National Natural Science Foundation of China(Nos.U23A20672,52171270,51879168)the PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML20240001,GML2024009)。
文摘We have described in detail the effects of nano-SiO_(2),nano-CaCO_(3),carbon nanotubes,and nano-Al_(2)O_(3) on geopolymer concrete from the perspectives of macro mechanics and microstructure.The existing research results show that the mechanism of nano-materials on geopolymer concrete mainly includes the filling effect,nucleation effect,and bridging effect,the appropriate amount of nano-materials can be used as fillers to reduce the porosity of geopolymer concrete,and can also react with Ca(OH)2 to produce C-S-H gel,thereby improving the mechanical properties of geopolymer concrete.The optimum content of nano-SiO_(2) is between 1.0%and 2.0%.The optimum content of nano-CaCO_(3) is between 2.0%and 3.0%.The optimum content of carbon nanotubes is between 0.1%and 0.2%.The optimum content of nano-Al_(2)O_(3) is between 1.0%and 2.0%.The main problems existing in the research and application of nanomaterial-modified geopolymer concrete are summarized,which lays a foundation for the further application of nanomaterial in geopolymer concrete.
基金supported by the Science and Technology Project of Henan Province(No.222102210081).
文摘Joint Multimodal Aspect-based Sentiment Analysis(JMASA)is a significant task in the research of multimodal fine-grained sentiment analysis,which combines two subtasks:Multimodal Aspect Term Extraction(MATE)and Multimodal Aspect-oriented Sentiment Classification(MASC).Currently,most existing models for JMASA only perform text and image feature encoding from a basic level,but often neglect the in-depth analysis of unimodal intrinsic features,which may lead to the low accuracy of aspect term extraction and the poor ability of sentiment prediction due to the insufficient learning of intra-modal features.Given this problem,we propose a Text-Image Feature Fine-grained Learning(TIFFL)model for JMASA.First,we construct an enhanced adjacency matrix of word dependencies and adopt graph convolutional network to learn the syntactic structure features for text,which addresses the context interference problem of identifying different aspect terms.Then,the adjective-noun pairs extracted from image are introduced to enable the semantic representation of visual features more intuitive,which addresses the ambiguous semantic extraction problem during image feature learning.Thereby,the model performance of aspect term extraction and sentiment polarity prediction can be further optimized and enhanced.Experiments on two Twitter benchmark datasets demonstrate that TIFFL achieves competitive results for JMASA,MATE and MASC,thus validating the effectiveness of our proposed methods.
基金Supported by Henan Provincial Science and Technology Research Project,No.242102310203.
文摘BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.AIM To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.METHODS Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were identified.Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.RESULTS Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.After treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia.Olanzapine effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.Ten core targets of olanzapine were involved in several key pathways.CONCLUSION The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.
基金financial support from the National Natural Science Foundation of China(Nos.22108258 and 52003251)Program for Science&Technology Innovation Talents in Universities of Henan Province(24HASTIT004)+1 种基金Outstanding Youth Fund of Henan Scientific Committee(222300420085)Science and Technology Joint Project of Henan Province(222301420041)。
文摘Mixed matrix membranes(MMMs)have demonstrated significant promise in energy-intensive gas separations by amalgamating the unique properties of fillers with the facile processability of polymers.However,achieving a simultaneous enhancement of permeability and selectivity remains a formidable challenge,due to the difficulty of achieving an optimal match between polymers and fillers.In this study,we incorporate a porous carbon-based zinc oxide composite(C@ZnO)into high-permeability polymers of intrinsic microporosity(PIMs)to fabricate MMMs.The dipole–dipole interaction between C@ZnO and PIMs ensures their exceptional compatibility,mitigating the formation of non-selective voids in the resulting MMMs.Concurrently,C@ZnO with abundant interconnected pores can provide additional low-resistance pathways for gas transport in MMMs.As a result,the CO_(2) permeability of the optimized C@ZnO/PIM-1 MMMs is elevated to 13,215 barrer,while the CO_(2)/N_(2) and CO_(2)/CH_(4) selectivity reached 21.5 and 14.4,respectively,substantially surpassing the 2008 Robeson upper bound.Additionally,molecular simulation results further corroborate that the augmented membrane gas selectivity is attributed to the superior CO_(2) affinity of C@ZnO.In summary,we believe that this work not only expands the application of MMMs for gas separation but also heralds a paradigm shift in the application of porous carbon materials.
文摘To investigate the evolution of load-bearing characteristics of pre-stressed beams throughout their service life and to provide a basis for accurately assessing the actual working state of damaged pre-stressed concrete T-beams,destructive tests were conducted on full-scale pre-stressed concrete beams.Based on the measurement and ana-lysis of beam deflection,strain,and crack development under various loading levels during the research tests,combined with the verification coefficient indicators specified in the codes,the verification coefficients of bridges at different stages of damage can be examined.The results indicate that the T-beams experience complete,incom-plete linear,and non-linear stages during the destructive test process.In the complete linear elastic stage,both the deflection and bottom strain verification coefficients comply with the specifications,indicating a good structural load-bearing capacity no longer adheres to the code’s requirements.In the non-linear stage,both coefficients exhi-bit a sharp increase,resulting in a further decrease in the structure’s load-bearing capacity.According to the pro-visions of the current code,the beam can be in the incomplete linear stage when both values fall within the code’s specified range.The strain verification coefficient sourced from the compression zone at the bottom of theflange is not recommended for assessing the bridge’s load-bearing capacity.
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
基金supported by the National Natural Science Foundation of China(52303257,52321006,T2394480,and T2394484)the National Key R&D Program of China(Grant No.2023YFE0111500)+3 种基金Key Research&Development and Promotion of Special Project(Scientific Problem Tackling)of Henan Province(242102211090)the China Postdoctoral Science Foundation(2023TQ0300,and 2023M743171)the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(GZB20230666)College Student Innovation and Entrepreneurship Training Program of Zhengzhou University(202410459200)。
文摘Flexible wearable optoelectronic devices fabricated fromorganic–inorganic hybrid perovskites significantly accelerate the developmentof portable energy,biomedicine,and sensing fields,but their poor thermal stabilityhinders further applications.Conversely,all-inorganic perovskites possessexcellent thermal stability,but black-phase all-inorganic perovskite filmusually requires high-temperature annealing steps,which increases energy consumptionand is not conducive to the fabrication of flexible wearable devices.In this work,an unprecedented low-temperature fabrication of stable blackphaseCsPbI3perovskite films is demonstrated by the in situ hydrolysis reactionof diphenylphosphinic chloride additive.The released diphenyl phosphateand chloride ions during the hydrolysis reaction significantly lower the phasetransition temperature and effectively passivate the defects in the perovskitefilms,yielding high-performance photodetectors with a responsivity of 42.1 AW−1 and a detectivity of 1.3×10^(14)Jones.Furthermore,high-fidelity imageand photoplethysmography sensors are demonstrated based on the fabricated flexible wearable photodetectors.This work provides a newperspective for the low-temperature fabrication of large-area all-inorganic perovskite flexible optoelectronic devices.
文摘Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
基金Supported by Henan Province Key Research and Development Program,No.231111311000Henan Provincial Science and Technology Research Project,No.232102310411+2 种基金Henan Province Medical Science and Technology Key Project,No.LHGJ20220566 and No.LHGJ20240365Henan Province Medical Education Research Project,No.WJLX2023079Zhengzhou Medical and Health Technology Innovation Guidance Program,No.2024YLZDJH022.
文摘This study highlights the importance of identifying and addressing risk factors associated with wound complications following transtibial amputation in diabetic patients.These amputations,often necessitated by severe diabetic foot ulcers,carry significant risks of postoperative complications such as infection and delayed wound healing.Elevated hemoglobin A1c levels,indicative of poor glycemic control,and a history of kidney transplantation,due to required immunosuppressive therapy,are key factors influencing these outcomes.This paper emphasizes the need for enhanced glycemic management and personalized postoperative care,particularly for immunocompromised individuals,to minimize complications and improve patient prognosis.Future research should focus on prospective studies to validate targeted interventions and optimize care strategies,ultimately aiming to reduce the healthcare burden associated with diabetic foot complications.
文摘This letter compares the clinical efficacy and economic feasibility of the scoliocorrector fatma-UI(SCFUI)with direct vertebral rotation(DVR)in treating adolescent idiopathic scoliosis(AIS).SCFUI has shown promising results in threedimensional spinal correction,providing superior rotational alignment compared to DVR and achieving significant improvements in coronal and sagittal planes.Additionally,SCFUI’s advanced design reduces risks associated with AIS surgeries and enhances overall patient outcomes.Economic analysis reveals SCFUI as a cost-effective option,potentially lowering long-term healthcare costs by minimizing complications and revisions.Our findings suggest that SCFUI is a viable,innovative approach in AIS treatment,meeting clinical and economic demands in orthopedic care.
基金Supported by the Natural Science Foundation of Xiaogan,China,No.XGKJ2023010036.
文摘BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.
