As a promising candidate seed cell type in regenerative medicine,mesenchymal stem cells(MSCs)have attracted considerable attention.The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/...As a promising candidate seed cell type in regenerative medicine,mesenchymal stem cells(MSCs)have attracted considerable attention.The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders.In this review,we discussed the current knowledge of and advances in MSCs,including its basic biological properties,i.e.,multilineage differentiation,secretome,and immunomodulation.Specifically,on the basis of our previous work,we proposed three new concepts of MSCs,i.e.,“subtotipotent stem cell”hypothesis,MSC system,and“Yin and Yang”balance of MSC regulation,which may bring new insights into our understanding of MSCs.Furthermore,we analyzed data from the Clinical Trials database(http://clinicaltrials.gov)on registered clinical trials using MSCs to treat a variety of immune diseases,such as graft-versus-host disease,systemic lupus erythematosus,and multiple sclerosis.In addition,we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.展开更多
Remembrance activities can support the Culture of Care(CoC)in Laboratory Animal Science(LAS)not only by promoting a culture of respect,gratitude and thankfulness for animal life but also by helping the emotional proce...Remembrance activities can support the Culture of Care(CoC)in Laboratory Animal Science(LAS)not only by promoting a culture of respect,gratitude and thankfulness for animal life but also by helping the emotional processing and healing of lab animal researchers and animal facility staff.Even though remembrance activities are practiced in many parts of the world,we did not come across any reported cases in Sri Lanka before 2022.Therefore,here,we report on the various remembrance activities and practices observed within our local scientific community.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
This study explores whether the current external quality assessment(EQA)level and acceptable bias for basic semen analysis in China are clinically useful.We collected data of semen EQA from Andrology laboratories in t...This study explores whether the current external quality assessment(EQA)level and acceptable bias for basic semen analysis in China are clinically useful.We collected data of semen EQA from Andrology laboratories in the Hunan Province(China)in 2022 and searched for data in the published literature from January2000 to December 2023 in China.On the basis of these data,we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics.We compared these findings with quality specifications based on biological variation from optimal,desirable,and minimum levels of bias to seek a unified and more suitable semen EQAbias evaluation standard for China's national conditions.Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories,ranging from 8.2%to 56.9%.A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility(PR),whereas 100.0%and 75.0%of laboratories met only the minimum quality specifications for sperm concentration and total motility(nonprogressive[NP]+PR),respectively.The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification,whereas the Z value for PR was equivalent only to the minimum performance specification.This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation.These specifications should be unified among external quality control(EQC)centers based on biological variation.展开更多
Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesi...Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.展开更多
Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles ...Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.展开更多
Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA...Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.展开更多
The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epid...As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
The proliferation of carrier aircraft and the integration of unmanned aerial vehicles(UAVs)on aircraft carriers present new challenges to the automation of launch and recovery operations.This paper investigates a coll...The proliferation of carrier aircraft and the integration of unmanned aerial vehicles(UAVs)on aircraft carriers present new challenges to the automation of launch and recovery operations.This paper investigates a collaborative scheduling problem inherent to the operational processes of carrier aircraft,where launch and recovery tasks are conducted concurrently on the flight deck.The objective is to minimize the cumulative weighted waiting time in the air for recovering aircraft and the cumulative weighted delay time for launching aircraft.To tackle this challenge,a multiple population self-adaptive differential evolution(MPSADE)algorithm is proposed.This method features a self-adaptive parameter updating mechanism that is contingent upon population diversity,an asynchronous updating scheme,an individual migration operator,and a global crossover mechanism.Additionally,comprehensive experiments are conducted to validate the effectiveness of the proposed model and algorithm.Ultimately,a comparative analysis with existing operation modes confirms the enhanced efficiency of the collaborative operation mode.展开更多
Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthi...Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.展开更多
Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating ...Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating neurological disorders and brain cancer.Additionally,this mechanism enhances the effectiveness of magnetic-guided drug delivery.The alternating magnetic field is applied to control the directions of the MNPs to target the tumor cells.This study approaches the radiotherapy techniques of magnetic hyperthermia therapy(MHT),wherein the thermal radiative heat transfer effect is applied to achieve homogenous heating to destroy cancer cells.MNPs are injected through the cerebrospinal fluid(CSF)transport in the glymphatic system.The elastic properties of the cerebral arteries cause peristaltic propulsion for the resulting nanofluid.Therefore,the effective Maxwell model for the nanofluid thermal conductivity is selected.The nanofluid governing equations are solved using the perturbation technique under small wavelength number and long wavelength approximation with small Reynolds number.Additionally,the effects of thermal slip and elastic properties boundary conditions are incorporated.The graphical results for the streamwise velocity,pressure,and temperature distributions are plotted using MATLAB package considering the different effects of the magnetic flux intensity,thermal radiation parameter,thermal slipping at boundaries,elastic wall properties,and nanoparticle concentration.The results demonstrate the strong impact of the magnetic field and radiation heating in terms of enhancing the nanofluid CSF flow behavior and destroying cancer.展开更多
Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical perf...BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.展开更多
基金the Key Program for Beijing Municipal Natural Science Foundation(No.7141006)National Collaborative Innovation Program(for Biotherapy)+2 种基金Beijing Science and Technology Project(No.Z151100001615-063)National Key Research and Development Program(Nos.2016YFA0101000 and 2016YFA0101003)PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(No.3332013141).
文摘As a promising candidate seed cell type in regenerative medicine,mesenchymal stem cells(MSCs)have attracted considerable attention.The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders.In this review,we discussed the current knowledge of and advances in MSCs,including its basic biological properties,i.e.,multilineage differentiation,secretome,and immunomodulation.Specifically,on the basis of our previous work,we proposed three new concepts of MSCs,i.e.,“subtotipotent stem cell”hypothesis,MSC system,and“Yin and Yang”balance of MSC regulation,which may bring new insights into our understanding of MSCs.Furthermore,we analyzed data from the Clinical Trials database(http://clinicaltrials.gov)on registered clinical trials using MSCs to treat a variety of immune diseases,such as graft-versus-host disease,systemic lupus erythematosus,and multiple sclerosis.In addition,we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.
文摘Remembrance activities can support the Culture of Care(CoC)in Laboratory Animal Science(LAS)not only by promoting a culture of respect,gratitude and thankfulness for animal life but also by helping the emotional processing and healing of lab animal researchers and animal facility staff.Even though remembrance activities are practiced in many parts of the world,we did not come across any reported cases in Sri Lanka before 2022.Therefore,here,we report on the various remembrance activities and practices observed within our local scientific community.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金supported by the Hunan Province Municipal Natural Science Foundation(2022JJ30018)the Hunan Province Health Commission Science Foundation(B202301037899)to WNL。
文摘This study explores whether the current external quality assessment(EQA)level and acceptable bias for basic semen analysis in China are clinically useful.We collected data of semen EQA from Andrology laboratories in the Hunan Province(China)in 2022 and searched for data in the published literature from January2000 to December 2023 in China.On the basis of these data,we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics.We compared these findings with quality specifications based on biological variation from optimal,desirable,and minimum levels of bias to seek a unified and more suitable semen EQAbias evaluation standard for China's national conditions.Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories,ranging from 8.2%to 56.9%.A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility(PR),whereas 100.0%and 75.0%of laboratories met only the minimum quality specifications for sperm concentration and total motility(nonprogressive[NP]+PR),respectively.The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification,whereas the Z value for PR was equivalent only to the minimum performance specification.This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation.These specifications should be unified among external quality control(EQC)centers based on biological variation.
基金supported by the National Natural Science Foundation of China(No.82360238,82071245)。
文摘Cancer pain is one of the most prevalent and debilitating symptoms in patients with advanced malignancies,arising from multifactorial mechanisms involving peripheral,central,and systemic pathways.Conventional analgesics,including opioids and nonsteroidal anti-inflammatory drugs,are often limited by their insufficient efficacy,tolerance,and risk of dependence.Traditional Chinese Medicine(TCM),characterized by its multi-component,multi-target,and systemic regulatory properties,has shown promising potential in cancer pain management.This review provides a comprehensive overview of the clinical classification and underlying mechanisms of cancer pain(including nerve infiltration,dysregulation of inflammatory mediators and ion channels,central sensitization,neuro-immune crosstalk,metabolic reprogramming,and gut-brain axis impairment),as well as the analgesic effects of representative TCM agents in cancer pain management.For example,bioactive components such as tetrahydroberberine,levo-tetrahydropalmatine,and piperine exert analgesic effects,thereby improving the quality of life of patients by inhibiting inflammatory cascades,regulating neurotransmitter systems,and preserving neural integrity.Commonly used preclinical models,including bone cancer pain,pancreatic cancer pain,and chemotherapy-induced peripheral neuropathy models,are summarized for their utility in mechanistic studies and efficacy evaluations.This review also discusses the current limitations of clinical evidence,such as small sample sizes,short follow-up periods,and limited translation from animal models,alongside major challenges in standardization,mechanistic elucidation,and clinical trial design.Future directions should focus on precise pain phenotyping,integrated multi-target interventions,rigorous efficacy safety validation,and innovations in drug delivery to facilitate the standardization and global adoption of TCM in cancer pain management.
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
基金supported by grant from the National Key Technology Support Program of the Ministry of Science and Technology of China(No.2021ZD0203204)。
文摘Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.
基金supported by the Natural Science Foundation of Beijing Municipality(No.F252065)the National Natural Science Foundation of China(No.32271190,32571323)the STI 2030 Major Project(No.2021ZD0203202)。
文摘Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
基金supported by grants from the Applied Basic Research Foundation of Yunnan Province(202301AT070095)the Candidate Talents Training Fund of Yunnan Province(H-2024069)。
文摘As oncologic therapies continue to advance,the overall survival of cancer patients has markedly increased.Nevertheless,virtually every anticancer treatment modality is accompanied by some degree of cardiotoxicity.Epidemiological data indicate that approximately 30%of cancer survivors ultimately die from cardiovascular disease.Among the cardiotoxic agents,the anthracycline doxorubicin(DOX)is the most widely used.It effectively suppresses a variety of malignant tumors——including breast cancer,lymphoma,and acute leukemia——but its cardiac toxicity limits further escalation of clinical dosing.Literature reports identify a cumulative dose of≥250 mg/m²as the threshold of high risk,with roughly 25%of patients receiving DOX developing varying degrees of myocardial injury;severe cases progress to heart failure.Even at cumulative doses below the traditional safety limit,some patients exhibit cardiac dysfunction after the first administration,suggesting that cardiotoxicity is not solely a linear function of dose.DOX related cardiotoxicity can be classified as acute(hours to days after administration),sub acute(weeks to months),and chronic/late onset(years later).Most patients initially exhibit only mild reductions in left ventricular ejection fraction(LVEF)or subtle abnormalities in global longitudinal strain(GLS),often without symptoms.Recently,cardiac biomarkers(cTn,NT proBNP)combined with high sensitivity echocardiography(speckle tracking)have been recommended for monitoring high risk individuals,enabling detection of subclinical injury before overt LVEF decline.Currently,several preventive and therapeutic approaches are used in clinical practice,which can be summarized into the following four points.(1)Dose limitation and administration strategies:fractionated low dose regimens,liposomal encapsulation,or continuous infusion lower peak plasma concentrations,thereby reducing cardiac exposure.(2)Pharmacologic prophylaxis:βblockers(e.g.,carvedilol)and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials,though results remain inconsistent and require larger confirmatory studies.(3)Metabolic targeted interventions:animal experiments indicate that activation of PPARαor supplementation with L carnitine restores fatty acid oxidation and improves ATP generation,suggesting metabolic modulators as promising cardioprotective candidates.(4)Lifestyle modifications:regular aerobic exercise up regulates mitochondrial biogenesis genes(PGC-1α)and reduces reactive oxygen species(ROS)production;small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation.However,DOX-induced cardiotoxicity has not been effectively controlled,indicating that the core mechanism underlying DOX‑related cardiac toxicity remains unidentified.Cardiomyocytes are high energy demand cells,and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity.DOX disrupts myocardial metabolic balance through several interrelated pathways.(1)Oxidative stress and mitochondrial damage:DOX generates abundant ROS within cells,leading to mitochondrial membrane potential loss,lipid peroxidation,and iron accumulation,which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency.(2)Autophagy dysregulation:DOX interferes with autophagic flux,preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses.(3)Inflammation and cytokine release:oxidative stress activates NF‑κB,up-regulating pro inflammatory cytokines such as TNF‑αand IL-6,creating a chronic inflammatory microenvironment that weakens myocardial contractility.(4)Epigenetic modifications:studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes,affecting the expression of key metabolic genes(e.g.,PGC-1α,CPT-1)and further inhibiting fatty acidβoxidation.These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis,manifested by an elevated lactate/pyruvate ratio,accumulation of medium chain acyl carnitines,and a pronounced decline in ATP production.The resulting energy deficit precipitates left ventricular contractile dysfunction and,ultimately,heart failure.Despite extensive basic and clinical research on DOX cardiotoxicity,a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking.This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury,thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury,we can move toward safer chemotherapy protocols that achieve“cure cancer without harming the heart”.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
文摘The proliferation of carrier aircraft and the integration of unmanned aerial vehicles(UAVs)on aircraft carriers present new challenges to the automation of launch and recovery operations.This paper investigates a collaborative scheduling problem inherent to the operational processes of carrier aircraft,where launch and recovery tasks are conducted concurrently on the flight deck.The objective is to minimize the cumulative weighted waiting time in the air for recovering aircraft and the cumulative weighted delay time for launching aircraft.To tackle this challenge,a multiple population self-adaptive differential evolution(MPSADE)algorithm is proposed.This method features a self-adaptive parameter updating mechanism that is contingent upon population diversity,an asynchronous updating scheme,an individual migration operator,and a global crossover mechanism.Additionally,comprehensive experiments are conducted to validate the effectiveness of the proposed model and algorithm.Ultimately,a comparative analysis with existing operation modes confirms the enhanced efficiency of the collaborative operation mode.
基金supported by Project to Make Multi-Ministerial National Biological Research Resources More Advanced Program,Korea Environment Industry&Technology Institute,and funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.
基金Fundación Mujeres por Africa for supporting this work through the fellowship awarded to her。
文摘Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating neurological disorders and brain cancer.Additionally,this mechanism enhances the effectiveness of magnetic-guided drug delivery.The alternating magnetic field is applied to control the directions of the MNPs to target the tumor cells.This study approaches the radiotherapy techniques of magnetic hyperthermia therapy(MHT),wherein the thermal radiative heat transfer effect is applied to achieve homogenous heating to destroy cancer cells.MNPs are injected through the cerebrospinal fluid(CSF)transport in the glymphatic system.The elastic properties of the cerebral arteries cause peristaltic propulsion for the resulting nanofluid.Therefore,the effective Maxwell model for the nanofluid thermal conductivity is selected.The nanofluid governing equations are solved using the perturbation technique under small wavelength number and long wavelength approximation with small Reynolds number.Additionally,the effects of thermal slip and elastic properties boundary conditions are incorporated.The graphical results for the streamwise velocity,pressure,and temperature distributions are plotted using MATLAB package considering the different effects of the magnetic flux intensity,thermal radiation parameter,thermal slipping at boundaries,elastic wall properties,and nanoparticle concentration.The results demonstrate the strong impact of the magnetic field and radiation heating in terms of enhancing the nanofluid CSF flow behavior and destroying cancer.
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
文摘BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.
