As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewe...As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewed commitment to ethical and scientific excellence in animal-based research.Throughout 2025,PALAS has continued to strengthen the laboratory animal science community by advancing education,capacity building,policy advocacy,and regional cooperation.These efforts underscore PALAS’vital role in shaping a culture of responsible animal research aligned with international standards.展开更多
Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endo...Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.展开更多
This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular st...Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in m...BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).展开更多
The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore functio...The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).展开更多
Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provid...Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.展开更多
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
Objective:To analyse the prevalence of serotypes,antibiotic resistance,and virulence genes of Group B Streptococcus(GBS)strains isolated from pregnant women at 35-37 weeks of gestation in Ho Chi Minh City,Vietnam,from...Objective:To analyse the prevalence of serotypes,antibiotic resistance,and virulence genes of Group B Streptococcus(GBS)strains isolated from pregnant women at 35-37 weeks of gestation in Ho Chi Minh City,Vietnam,from January 2022 to January 2023.Methods:GBS strains were isolated through selective culture methods and confirmed by PCR.Serotyping,virulence gene detection,and antibiotic susceptibility testing were performed using PCR,gel electrophoresis techniques and Kirby-Bauer test.Results:Totally,61 GBS isolated from 300 participants have been identified including seven GBS serotypes(Ⅰa,Ⅰb,Ⅱ,Ⅲ,Ⅳ,Ⅴ,andⅥ).SerotypesⅦ,Ⅷ,andⅨwere not detected in the study population.Antibiotic resistance patterns varied:13.1%of isolates were fully susceptible,while the majority showed multi-drug resistance,with 34.4%resistant to three antibiotics.SerotypeⅠa demonstrated high susceptibility(35.7%),while serotypeⅢshowed extensive resistance,with 87.5%being resistant to at least three antibiotics.All strains are susceptible to vancomycin andβ-lactams susceptibility also remained high,but resistance to clindamycin,erythromycin,and tetracycline was high(>65%).The virulence genes scpB,cylB,fbsB,and cfb were highly prevalent(90%-100%),indicating their potential for vaccine and diagnostic development.Conclusions:Our findings provide valuable insights into GBS serotypes,resistance,and virulence factors,contributing to community monitoring,preventive measures,diagnostics,and vaccine development.However,the limited sample size necessitates further research.展开更多
Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functi...Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.展开更多
Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always...Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always struggle to balance mechanical properties and thermal insulation,resulting in their inability to meet the demands for both washing resistance and personal protection.Herein,inspired by the natural spring-like structures of cucumber tendrils,a superelastic and washable micro/nanofibrous sponge(MNFS)based on biomimetic helical fibers is directly prepared utilizing multiple-jet electrospinning technology for high-performance thermal insulation.By regulating the conductivity of polyvinylidene fluoride solution,multiple-jet ejection and multiple-stage whipping of jets are achieved,and further control of phase separation rates enables the rapid solidification of jets to form spring-like helical fibers,which are directly entangled to assemble MNFS.The resulting MNFS exhibits superelasticity that can withstand large tensile strain(200%),1000 cyclic tensile or compression deformations,and retain good resilience even in liquid nitrogen(-196℃).Furthermore,the MNFS shows efficient thermal insulation with low thermal conductivity(24.85 mW m^(-1)K^(-1)),close to the value of dry air,and remains structural stability even after cyclic washing.This work offers new possibilities for advanced fibrous sponges in transportation,environmental,and energy applications.展开更多
Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Metho...Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Methods This was an ambispective cohort study. A total of 85 older adults participating in the Chronic Heart Failure Program at Guillermo Almenara National Hospital were included. Each had an initial frailty assessment, forming two cohorts: frail and non-frail older adults. Medical records were reviewed, and patients were followed for one year to track events of interest(hospitalization and mortality). Overall survival and risk factors for hospitalization and death were determined.Results During follow-up, 15.3% of the older adults died, and frailty was identified in 58.8% of the patients. Overall survival using the Kaplan-Meier method was 96.5% at 3 months after entering the Chronic Heart Failure Program;92.9% at 6 months;and85.9% at one year. Multivariate analysis using Poisson regression found that frailty was not a risk factor for hospitalization(a RR =0.92;95% CI: 0.42–2.03). Survival analysis using the Cox proportional hazards model showed that frailty was also not a risk factor for mortality after one year of follow-up(a HR = 1.32;95% CI: 0.27–6.53).Conclusions Our research does not confirm frailty as a risk factor for hospitalization or mortality in older adults enrolled in the“Chronic Heart Failure Program” after one year of follow-up.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Curre...Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.展开更多
Objectives:Early detection of hepatocellular carcinoma(HCC)is a significant challenge due to the limited sensitivity of alpha-fetoprotein(AFP).This study aimed to assess serum-derived extracellular vesicleencapsulated...Objectives:Early detection of hepatocellular carcinoma(HCC)is a significant challenge due to the limited sensitivity of alpha-fetoprotein(AFP).This study aimed to assess serum-derived extracellular vesicleencapsulated GULP PTB domain-containing engulfment adaptor 1(EV-GULP1)as a novel,noninvasive biomarker for HCC detection and prognosis,leveraging the potential of tumor-specific molecules carried by small extracellular vesicles(EVs).Methods:The study utilized both internal and external cohorts of HCC patients and controls.Small EVs were isolated from serum samples,then characterized and validated to confirm their identity.The expression levels of EV-GULP1 were quantified using quantitative reverse transcription polymerase chain reaction(qRT-PCR).Results:EVGULP1 expression was found to be significantly higher in HCC patients,including those with early-stage disease,when compared to control groups.It demonstrated superior diagnostic accuracy over AFP,achieving an area under the curve(AUC)of 0.919,and was particularly effective in detecting AFP-negative cases.Furthermore,high EV-GULP1 expression correlated with worse overall and disease-free survival outcomes.Conclusion:These findings highlight EV-GULP1 as a highly promising noninvasive biomarker for hepatocellular carcinoma.It offers improved diagnostic accuracy for early detection and better risk stratification for prognosis compared to the current standard,AFP.展开更多
Background:This paper aimed to systematically review the literature regarding the effects of resistance training(RT)performed at longer-muscle length(LML)versus shorter-muscle length(SML)on proxy measurements for long...Background:This paper aimed to systematically review the literature regarding the effects of resistance training(RT)performed at longer-muscle length(LML)versus shorter-muscle length(SML)on proxy measurements for longitudinal hypertrophy.Methods:We included studies that satisfied the following criteria:(1)be a resistance training intervention with a comparison of LML vs SML-RT;(2)assess both fascicle length(FL)and muscle size pre-and post-intervention;(3)involve healthy adults aged≥18 years;(4)be published in an English-language journal,and;(5)have a minimum training intervention duration of 4 weeks.Three databases were searched in February 2024(Google Scholar,PubMed/Medline,Scopus)for relevant articles,alongside'forward'and'backward'citation searching of articles included and additions via authors'personal knowledge.The results of studies were described narratively,compared,and contrasted.Eight studies met the inclusion criteria,totaling a sample size of 120.Results:Our results suggest that both muscle size and fascicle length increases may be greater following LML-RT versus SML-RT,suggesting LML-RT may lead to greater longitudinal hypertrophy than SML-RT.Notably,evidence is largely mixed;no studies to date have attempted to estimate serial sarcomere number changes from LML versus SML-RT,and all but one study used linear extrapolation methods to estimate FL,which has questionable validity.Therefore,the structural adaptations underlying hypertrophy from LML-RT remain undetermined.Conclusion:In conclusion,results suggest that LML-RT may be superior to SML-RT for inducing muscle hypertrophy and,more specifically,longitudinal growth,though evidence is mixed.展开更多
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
文摘As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewed commitment to ethical and scientific excellence in animal-based research.Throughout 2025,PALAS has continued to strengthen the laboratory animal science community by advancing education,capacity building,policy advocacy,and regional cooperation.These efforts underscore PALAS’vital role in shaping a culture of responsible animal research aligned with international standards.
文摘Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
基金supported by the National Italian Research Council(CNR)“Progetto DSB.AD007.305.001”to Monica Rinaldi。
文摘Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the award W81XWH1910309 (to HF) from the Department of Defensethe award R01-AG075092-01 (to HF)+2 种基金the award RF1AG063521 from the National Institute of Aging at the National Institutes of Healththe Neurological Research Institute Seed grant (to HF) from The Ohio State Universitythe Summer Undergraduate Research Fellowship (to NS) from The Ohio State University Chronic Brain Injury Discovery Theme
文摘BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).
基金supported by the University of Padua(to MR)by the project“RIPANE”of the Italian Ministry of Defense(to CM)by Cariparo Foundation(to CM)。
文摘The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).
基金supported by grants from Guangdong Basic and Applied Basic Research Foundation,No.2021A1515110801(to SW)the National Natural Science Foundation of China,No.82301511(to SW)+1 种基金“Double First-Class”Construction Project of NPU,Nos.0515023GH0202320(to JC),0515023SH0201320(to JC)973 Program,No.2011CB504100(to JC).
文摘Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
基金supported by the National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
文摘Objective:To analyse the prevalence of serotypes,antibiotic resistance,and virulence genes of Group B Streptococcus(GBS)strains isolated from pregnant women at 35-37 weeks of gestation in Ho Chi Minh City,Vietnam,from January 2022 to January 2023.Methods:GBS strains were isolated through selective culture methods and confirmed by PCR.Serotyping,virulence gene detection,and antibiotic susceptibility testing were performed using PCR,gel electrophoresis techniques and Kirby-Bauer test.Results:Totally,61 GBS isolated from 300 participants have been identified including seven GBS serotypes(Ⅰa,Ⅰb,Ⅱ,Ⅲ,Ⅳ,Ⅴ,andⅥ).SerotypesⅦ,Ⅷ,andⅨwere not detected in the study population.Antibiotic resistance patterns varied:13.1%of isolates were fully susceptible,while the majority showed multi-drug resistance,with 34.4%resistant to three antibiotics.SerotypeⅠa demonstrated high susceptibility(35.7%),while serotypeⅢshowed extensive resistance,with 87.5%being resistant to at least three antibiotics.All strains are susceptible to vancomycin andβ-lactams susceptibility also remained high,but resistance to clindamycin,erythromycin,and tetracycline was high(>65%).The virulence genes scpB,cylB,fbsB,and cfb were highly prevalent(90%-100%),indicating their potential for vaccine and diagnostic development.Conclusions:Our findings provide valuable insights into GBS serotypes,resistance,and virulence factors,contributing to community monitoring,preventive measures,diagnostics,and vaccine development.However,the limited sample size necessitates further research.
基金supported by the National Research Foundation of Korea(NRF),funded by the Ministry of Science and ICT(MSIT),Republic of Korea(grant numbers:RS-2022-NR070489 and RS-2023-00210847)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare,Republic of Korea(grant number HR21C1003).
文摘Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.
基金supported by Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2022QNRC001)the National Natural Science Foundation of China(No.52273053)the Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(No.21CGA41)。
文摘Extreme cold weather seriously harms human thermoregulatory system,necessitating high-performance insulating garments to maintain body temperature.However,as the core insulating layer,advanced fibrous materials always struggle to balance mechanical properties and thermal insulation,resulting in their inability to meet the demands for both washing resistance and personal protection.Herein,inspired by the natural spring-like structures of cucumber tendrils,a superelastic and washable micro/nanofibrous sponge(MNFS)based on biomimetic helical fibers is directly prepared utilizing multiple-jet electrospinning technology for high-performance thermal insulation.By regulating the conductivity of polyvinylidene fluoride solution,multiple-jet ejection and multiple-stage whipping of jets are achieved,and further control of phase separation rates enables the rapid solidification of jets to form spring-like helical fibers,which are directly entangled to assemble MNFS.The resulting MNFS exhibits superelasticity that can withstand large tensile strain(200%),1000 cyclic tensile or compression deformations,and retain good resilience even in liquid nitrogen(-196℃).Furthermore,the MNFS shows efficient thermal insulation with low thermal conductivity(24.85 mW m^(-1)K^(-1)),close to the value of dry air,and remains structural stability even after cyclic washing.This work offers new possibilities for advanced fibrous sponges in transportation,environmental,and energy applications.
文摘Objective To determine whether frailty is a risk factor for hospitalization and mortality in older adults enrolled in the "Chronic Heart Failure Program" at a hospital in Lima, Peru, between 2018–2021.Methods This was an ambispective cohort study. A total of 85 older adults participating in the Chronic Heart Failure Program at Guillermo Almenara National Hospital were included. Each had an initial frailty assessment, forming two cohorts: frail and non-frail older adults. Medical records were reviewed, and patients were followed for one year to track events of interest(hospitalization and mortality). Overall survival and risk factors for hospitalization and death were determined.Results During follow-up, 15.3% of the older adults died, and frailty was identified in 58.8% of the patients. Overall survival using the Kaplan-Meier method was 96.5% at 3 months after entering the Chronic Heart Failure Program;92.9% at 6 months;and85.9% at one year. Multivariate analysis using Poisson regression found that frailty was not a risk factor for hospitalization(a RR =0.92;95% CI: 0.42–2.03). Survival analysis using the Cox proportional hazards model showed that frailty was also not a risk factor for mortality after one year of follow-up(a HR = 1.32;95% CI: 0.27–6.53).Conclusions Our research does not confirm frailty as a risk factor for hospitalization or mortality in older adults enrolled in the“Chronic Heart Failure Program” after one year of follow-up.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by the National Natural Science Foundation of China(32325024,32400981,32222024,32271224,32471228,and 82270891)the National Key Research and Development Program of China(2023YFA1800400)+3 种基金the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG22)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0507300)the ECNU public platform for Innovation(011)the instruments sharing platform of School of Life Sciences.
文摘Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.
基金supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare,Republic of Korea(HR21C1003)the Bio and Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science and ICT(RS-2022-NR070489,RS-2023-00210847,RS-2024-00422549,RS-2024-00463331,RS-2025-00521818,and RS-2025-00562556).
文摘Objectives:Early detection of hepatocellular carcinoma(HCC)is a significant challenge due to the limited sensitivity of alpha-fetoprotein(AFP).This study aimed to assess serum-derived extracellular vesicleencapsulated GULP PTB domain-containing engulfment adaptor 1(EV-GULP1)as a novel,noninvasive biomarker for HCC detection and prognosis,leveraging the potential of tumor-specific molecules carried by small extracellular vesicles(EVs).Methods:The study utilized both internal and external cohorts of HCC patients and controls.Small EVs were isolated from serum samples,then characterized and validated to confirm their identity.The expression levels of EV-GULP1 were quantified using quantitative reverse transcription polymerase chain reaction(qRT-PCR).Results:EVGULP1 expression was found to be significantly higher in HCC patients,including those with early-stage disease,when compared to control groups.It demonstrated superior diagnostic accuracy over AFP,achieving an area under the curve(AUC)of 0.919,and was particularly effective in detecting AFP-negative cases.Furthermore,high EV-GULP1 expression correlated with worse overall and disease-free survival outcomes.Conclusion:These findings highlight EV-GULP1 as a highly promising noninvasive biomarker for hepatocellular carcinoma.It offers improved diagnostic accuracy for early detection and better risk stratification for prognosis compared to the current standard,AFP.
文摘Background:This paper aimed to systematically review the literature regarding the effects of resistance training(RT)performed at longer-muscle length(LML)versus shorter-muscle length(SML)on proxy measurements for longitudinal hypertrophy.Methods:We included studies that satisfied the following criteria:(1)be a resistance training intervention with a comparison of LML vs SML-RT;(2)assess both fascicle length(FL)and muscle size pre-and post-intervention;(3)involve healthy adults aged≥18 years;(4)be published in an English-language journal,and;(5)have a minimum training intervention duration of 4 weeks.Three databases were searched in February 2024(Google Scholar,PubMed/Medline,Scopus)for relevant articles,alongside'forward'and'backward'citation searching of articles included and additions via authors'personal knowledge.The results of studies were described narratively,compared,and contrasted.Eight studies met the inclusion criteria,totaling a sample size of 120.Results:Our results suggest that both muscle size and fascicle length increases may be greater following LML-RT versus SML-RT,suggesting LML-RT may lead to greater longitudinal hypertrophy than SML-RT.Notably,evidence is largely mixed;no studies to date have attempted to estimate serial sarcomere number changes from LML versus SML-RT,and all but one study used linear extrapolation methods to estimate FL,which has questionable validity.Therefore,the structural adaptations underlying hypertrophy from LML-RT remain undetermined.Conclusion:In conclusion,results suggest that LML-RT may be superior to SML-RT for inducing muscle hypertrophy and,more specifically,longitudinal growth,though evidence is mixed.
基金supported by European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
