摘要：Graft procurement in adult living donor liver transplantation(LDLT)faces persistent challenges in balancing volumetric adequacy and donor safety.This study introduces two-stage portal vein ligation and reperfusion for graft procurement in LDLT(PVLR-LT),which aims to expand the left lateral lobe for achieving adequate grafts,thereby cir-cumventing technical and anatomical limitations of conventional approaches.In a rat model,the PVLR-LT group underwent selective portal vein ligation(step Ⅰ)to induce targeted hypertrophy,followed by reperfusion and transplantation(step Ⅱ).Outcomes were compared among PVLR-LT,negative controls,and standard-volume controls.Staged portal flow modulation effectively redistributed hepatic mass allocation,yield-ing grafts with graft recipient weight ratio approximately double that of negative con-trols and equivalent to standard-volume controls.Donors experienced no mortality,with only transient enzyme elevation.Recipient survival in the PVLR-LT group signifi-cantly exceeded that of the negative control group and was non-inferior to that of the standard-volume control group,while hepatic enzyme peaks were markedly lower than those in standard-volume control recipients.This study provides a promising proof of concept,establishing the feasibility of using PVLR-LT to convert the surgically straight-forward left lateral segment into right lobe-sized grafts through staged portal flow modulation and demonstrating the translational potential for laparoscopic LDLT.

摘要：Background:Human adipose-derived stem cells(hADSCs)are seed cells with applica-tion prospects in cartilage repair.However,the mechanism of hADSC chondrogenic differentiation is still unclear.This study identifies a novel circRNA,circNR3C2,which is significantly upregulated during the chondrogenic differentiation of hADSCs. Methods:To analyze their role in hADSC chondrogenic differentiation,hADSCs were separated and identified by flow cytometry.Thereafter,we conducted Alcian Blue staining to assess chondrogenic differentiation levels.Additionally,RT-qPCR was car-ried out to detect levels of the cartilage-related genes COL2,Aggrecan and SOX9.Moreover,overlapping target SOX9 and circNR3C2 miRNAs were detected by bioin-formatics and luciferase analyses.Finally,the role of circNR3C2 was confirmed in vivo using animal models. Results:We confirmed that the cell surface receptors CD44,CD90 and CD105 were positively expressed on hADSCs,and their cartilage differentiation levels dramati-cally increased after 2weeks.Expression of the cartilage-related genes COL2 and Aggrecan and circNR3C2 also markedly increased.CircNR3C2 overexpression en-hanced cartilage differentiation of hADSCs,while up-regulating COL2,SOX9 and Aggrecan.Bioinformatics analysis identified hsa-miR-647 as the target miRNA of circ-NR3C2 and SOX9.Hsa-miR-647 overexpression in hADSCs can antagonize the effect of circNR3C2 on chondrogenic differentiation,and reverse its effect on regulating the expression of COL2,Aggrecan,and SOX9.We also showed that hADSCs overexpress-ing circNR3C2 promote cartilage repair in vivo. Conclusions:We show that circNR3C2 modulates SOX9 expression to promote hsa-miR-647-mediated hADSC chondrogenic differentiation;targeting circNR3C2 may help to develop new treatments to manage cartilage-related disorders.

摘要：RNA molecules play diverse and essential roles in cellular processes beyond their well-known functions in gene expression and regulation.While ribosomal RNAs(rRNAs)have long been recognized as structural components of ribosomes,recent research has highlighted the importance of a distinct group of RNAs which directly compose the structures or organelles in mammalian cells.We refer to these as'organelle for-mation RNAs'.Specifically,the discovery of tubulin-associated lncRNA(TubAR),the first identified cytoskeleton-forming RNA,has expanded our understanding of RNA functionality;we now recognize'organelle formation RNAs'not only as regulatory molecules but also as direct structural components within cellular subunits.Other'or-ganelle formation RNAs'include paraspeckle-forming RNAs,nuclear speckle-forming RNAs,and nucleolus-forming RNAs.Various RNAs contribute to the formation of distinct cellular structures,while also participating in intricate intermolecular interac-tions.Understanding these molecules not only uncovers their fundamental roles in cellular physiology but also suggests potential applications in the treatment of related diseases.By examining the latest advancements and methodologies in organelle for-mation RNA research,this review provides a comprehensive overview of the intricate mechanisms of these RNAs and future directions in the field.

摘要：Multimorbidity-the co-occurrence of more than two chronic conditions in the same individual—is associated with premature death,diminished function,reduced quality of life,and increased societal burden.This complex state involves dynamic interac-tions across multiple conditions,organ systems,and physiological pathways;yet re-search progress remains constrained by inadequate animal models that recapitulate human complexity.This review summarizes the predominant patterns of multimorbid-ity and evaluates current animal models spanning invertebrates,rodents,and large mammals.While no single model fully captures the multifaceted nature of human multimorbidity,we propose several strategic directions to address existing limitations:implementing a cross-species validation framework(from simple organisms to rodents to large mammals),standardizing protocols integrating multimodal risk factors,de-veloping advanced non-animal models,and enhancing ethical oversight.Advancing multimorbidity models is crucial for decoding disease interactions and accelerating translation of research findings into improved patients outcomes.

摘要：Background:An arterial stiffness is an indicator of many cardiovascular diseases.The temporal position of systolic blood pressure(BP)on aorta pulse waveform is assumed to gradually shift on the waveform in response to increasing/decreasing vascular stiff-ness.The animal model of rats and invasive methods that cannot be used in humans was applied to test the assumption on arterial pulse waveform(APW)of anesthetized rat.The aim of this study was to characterize the temporal movement of diastolic and systolic pressures on the APW of anesthetized rats during increasing/decreasing vascular stiffness. Methods:The right jugular vein of anesthetized normotensive and spontaneously hy-pertensive rats was cannulated for intravascular administration of vascularly active compounds to alter systolic pressure and vascular stiffness.The left carotid artery was cannulated to detect APW,from which numerous APW parameters were evaluated. Results:During increases/decreases in systolic BP or stiffness,the temporal posi-tion of diastolic BP of individual heartbeats di-gitally shifted on the APW between two temporal positions～8-12 ms apart,and the temporal position of systolic BP on the APW did not gradually shift during increases/decreases in vascular stiffness,as expected,but oscillated between constant di-gital,tri-gital,or tetra-gital temporal positions. Conclusions:Introducing new APW parameters,n-gital systolic BP fluctuations on rat APW were found.Fluctuations in n-gital were approximately constant during large changes in systolic pressure despite significant changes in augmentation index and cardiovascular stiffness,which may challenge the assumption of a gradual temporal location of systolic pressure on rat APW under these conditions.

摘要：ZSF1 lean rats are widely used as controls in cardiometabolic studies involving ZSF1 obese rats,which develop a cardiometabolic syndrome and diastolic dysfunction at a young age due to a double leptin receptor mutation(Leprcp and Leprfa).Although,lean littermates show no overt signs of cardiometabolic disease or diastolic impact,they belong to one of three genotypic variants,two of which carry one of the mutant Lepr alleles and,thus,doubt has been raised about their suitability as healthy controls.We compared 32-week-old female ZSF1 lean and Wistar rats regarding physiological,myocardial,vascular,skeletal muscle,and mitochondrial characteristics.Lean rats showed lower body weight but increased heart,kidney,and skeletal muscle mass.Despite thicker ventricular walls,systolic and diastolic function were preserved.Hemodynamically measured contractility was higher as underpinned by a higher mitochondrial respiratory capacity of LV fibers.However,left ventricular filling pressure was elevated,accompanied by increased ventricular stiffness.Endothelial function was preserved,but smooth muscle responsiveness was reduced,indicated by impaired SNP-induced relaxation.Passive vascular stiffness mediated by collagenous fibers was significantly higher in lean rats.Skeletal muscle function was mostly preserved,though maximal specific force of the EDL was reduced.Taken together,ZSF1 lean rats are physiologically different from Wistar rats as they display enlarged myocardial dimensions accompanied by increased blood pressure and an incipient diastolic and vascular stiffness.Therefore,our data indicate an early phase of passive compliance disorder in ZSF1 lean animals,which might become more pronounced at an advanced age.

摘要：Background:Diabetes,a metabolic disease marked by endocrine dysfunctions,signif-icantly impacts oxidative stress pathways.This study explores the protective effects of lemongrass extract(LE),citral,and lemongrass extract-synthesized silver nanopar-ticles(LE-AgNP)against hyperglycemia-induced oxidative stress by modulating the Nrf2 pathway,which is crucial for antioxidant responses. Methods:Various techniques characterized the nanoparticles,including ultravio-let-visible spectroscopy,dynamic light scattering,zeta potential analysis,Fourier-transform infrared spectroscopy,scanning electron microscopy and transmission electron microscopy.Seventy rats,divided into seven groups,were used for in vivo experiments.Type 2 diabetes was induced using streptozotocin(65 mg/kg)and nicoti-namide(90mg/kg).After six weeks,biochemical parameters such as total antioxidant capacity,malondialdehyde,Nrf2,and Nrf2 miRNA were evaluated in pancreas tissue and blood serum,along with serum blood glucose levels. Results:LE-AgNP significantly improved weight gain,reduced food and water intake,and lowered blood glucose levels in diabetic rats.LE and citral did not significantly alter these parameters but prevented the decline in Nrf2 gene expression.LE-AgNP showed a significant increase in Nrf2 gene expression compared to the diabetic con-trol group. Conclusions:This study highlights the potential of LE,citral,and especially LE-AgNP in mitigating oxidative stress induced by diabetes.LE-AgNP demonstrated superior therapeutic benefits,including improved oxidative stress conditions and hypoglyce-mic effects.

摘要：Background:The current understanding of diabetic kidney disease(DKD)has sig-nificant gaps regarding the underlying pathogenesis.In this study,we aimed to char-acterize the temporal progression of DKD using a state-of-the-art mouse model of hypertension-accelerated disease,integrating kidney biomarker analysis,histopathol-ogy,and glomerular transcriptomic profiling. Methods:Female diabetic db/db mice received a single intravenous dose of adeno-associated virus-mediated renin overexpression(ReninAAV,week 5)and underwent uninephrectomy(UNx,week 4).db/db UNx-ReninAAV mice were terminated at weeks 1,4,8,and 12(n=7-8 per group).Female db/m mice were used as healthy controls.Study endpoints included plasma and urine biochemistry,glomerulosclerosis scoring,quantitative kidney histology,and RNA sequencing of glomeruli isolated using laser-capture microdissection. Results:db/db UNx-ReninAAV mice developed progressive albuminuria(from week 4)and glomerulosclerosis(from week 8).A pathway analysis of clustered gene regula-tions revealed broad glomerular transcriptome perturbations with signatures of in-creased extracellular matrix(ECM)turnover from week 8 and early onset of metabolic dysfunction.Markers of glomerular cell types and injury exhibited temporal regula-tion over the course of DKD,with early and sustained downregulation of endothelial markers,heterogeneous regulation of podocyte markers,and significant mesangial and parietal epithelial aberrations.Furthermore,the upregulation of cell injury mark-ers confirmed progressive glomerular injury in the model. Conclusion:The db/db UNx-ReninAAV mouse model exhibits distinct temporal dy-namics in glomerular cell markers,metabolic dysregulation,ECM remodeling,and in-jury.Together,these results highlight the utility of the db/db UNx-ReninAAV model as a relevant preclinical platform for studying progressive DKD.

摘要：Background:Brachial plexus root avulsion(BPRA),a well-known form of peripheral nerve injury,results in motor function loss in the affected forelimb due to motoneu-ron(MN)death,which may be influenced by neuroinflammation following a lesion in the spinal cord.Although synthase-stimulator of interferon genes(STING)signaling can contribute to chronic inflammation and tissue damage in a number of pathologi-cal conditions,the essential role of STING signaling in BPRA remains to be reported.Based on our previous findings that the STING mRNA level is upregulated in the ante-rior horn of the segment of the affected spinal cords of mice with BPRA,STING may be associated with motor recovery in BPRA. Methods:In the present study,STING knockout transgenic mice were used to estab-lish a BPRA re-implantation model,which was followed by behavioral tests,histo-chemical staining and quantitative reverse transcription polymerase chain reaction. Results:The results demonstrated that STING deficiency can increase the body weight,promote motor recovery,decrease MN death,inhibit pyroptosis and neuro-inflammation,increase remyelination,and reduce the atrophy of the biceps brachii in mice with BPRA. Conclusion:These combined results suggest that inhibition of STING may be a prom-ising strategy for treating BPRA.

摘要：The FELASA 2025 Congress,themed"Reducing Severity in Animal Research,"con-vened global experts in laboratory animal sciences to discuss ethical advancements,welfare standards,and innovative practices.Key sessions highlighted the integration of the 3R principles(Replacement,Reduction,Refinement),with presentations ad-dressing challenges in immunology,Al-driven animal monitoring,and aseptic surgi-cal techniques.Notable lectures,including Prof.Stasinos Stavrianeas' exploration of zoology's origins and Dr.David Anderson's award-winning talk on squid welfare,em-phasized cultural relevance and ethical responsibility.The congress also prioritized sustainability through waste-reduction measures and digital tools like an official app for enhanced networking.Exhibitions showcased cutting-edge technologies,while workshops fostered hands-on skill development.By advocating openness and inter-disciplinary collaboration,FELASA 2025 aimed to advance humane and scientifically rigorous animal research practices globally.

摘要：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 commit-ment 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.

摘要：When it comes to journalism,in today's highly informationalized era,it is not unjustified for news reports to employ exaggerated or emo-tionally charged language to capture audience attention,as it is also natural for journalists to infuse their personal sentiments into their news articles.

摘要：The current anesthetic standard for laryngoscopy in rats utilizes injectable intraperi-toneal anesthesia.Injectable anesthesia is suboptimal for short procedures due to variability in anesthesia duration and anesthetic side effects.Conversely,inhalational gas anesthesia offers precise titration with a rapid onset and offset.However,its use during laryngoscopy has not been documented due to existing administration tech-niques obstructing direct visualization of the larynx.The technique described here al-lows real-time visualization of the rat larynx with concurrent administration of inhaled anesthetic gas.This method is particularly well-suited for recurrent laryngeal nerve or vocal fold pathology studies,where repeat visualization of the larynx is necessary.

摘要：Malaysia's commemoration of the second Asia Laboratory Animal Day(ALAD)in 2025 marked a notable step forward in strengthening national and regional labora-tory animal science,ethical governance,and humane research practices.Celebrated a day earlier on 28 November,an initiative led by the Laboratory Animal Science Association of Malaysia(LASAM),comprised a coordinated three-month programme from September to November.A series of targeted activities were conducted,includ-ing professional exchange visits,competency-based rodent care and use workshops,refinement-centred blood sampling training,and institutional lectures on ethics and welfare.These engagements involved researchers,technicians,ethics commit-tee members,and undergraduate trainees;reflecting ALAD's aim of fostering ethi-cal awareness and technical proficiency across all levels of research personnel.A major highlight of the campaign was the signing of a Memorandum of Understanding between LASAM and Universiti Teknologi MARA(UiTM),strengthening long-term collaboration in training,welfare standard harmonisation,and shared ethical govern-ance.The programme also delivered measurable outcomes:over 92％of participants improved their understanding of the 3Rs and humane endpoints,more than 95％at-tained competency in basic rodent handling,and national interest in laboratory animal science increased,as reflected by rising LASAM membership.Malaysia's ALAD initia-tives emphasise the importance of grassroots engagement,refinement-based train-ing,and strong institutional partnerships in advancing ethical and humane science.The country's experience provides a replicable framework for other Asian regions seeking to enhance welfare capacity,harmonise standards,and cultivate responsible research communities.Malaysia remains committed to supporting ALAD's ongoing mission to advance scientific integrity and animal welfare across Asia.

摘要：The One-Day Workshop on"Frontiers in Laboratory Animal Handling and Experimental Design:Bridging Ethics and Excellence"organized on the occasion of the Second Asia Laboratory Animal Day,offered a comprehensive learning experience that seamlessly integrated ethical principles,technical competencies,anatomical knowledge,and scientific methodology into a unified framework for responsible laboratory animal care.Centered around the theme"Good Science with Good Care,"the program highlighted that high-quality,reproducible research is achievable only when humane practices,strict adherence to regulatory guidelines,and thoughtful experimental planning form the foundation of all laboratory work.The workshop reinforced the idea that scientific excellence and animal welfare are not separate goals,but complementary pillars that together ensure ethical,efficient,and meaningful preclinical research.

摘要：Background:Chronic obstructive pulmonary disease(COPD)is a type of chronic res-piratory disease.Studies confirmed that ferroptosis was involved in the progression of COPD,and its related mechanism is not clear.The aim of this study was to identify ferroptosis-related genes and reveal its pathological application in COPD. Methods:First,we downloaded two datasets from the Gene Expression Omnibus(GEO)to obtain the differential genes of COPD.Ferroptosis-related genes were ob-tained from the ferroptosis database,FerrDb.Next,we obtained the key genes in COPD rat to identify potential biomarkers using quantitative real-time polymerase chain reaction.Ferroptosis and inflammation were assessed using hematoxylin and eosin staining,lung function tests,and transmission electron microscopy(TEM). Results:These results were used to construct a COPD risk model with six key genes and explore the immunological characteristics of these genes.The resulting mo-lecular subtype construction confirmed the importance of the key genes in COPD.Furthermore,we proved that ferroptosis occurred in the COPD rat model and identi-fied the six key genes in rat lung tissue.TEM showed significant functional impairment and structural alterations in mitochondria,which is the key site of ferroptosis. Conclusion:Our COPD risk model,incorporating six key genes,highlighted their im-munological roles in COPD using bioinformatics analysis and in vivo experiments.We hope to provide the basis for the treatment targeting ferroptosis in COPD.

摘要：Background:Diabetes mellitus(DM),a metabolic disorder that leads to chronic hy-perglycemia,is one of the topmost global public health concerns according to the International Diabetes Federation.Adropin is a peptide hormone that is primarily in-volved in energy homeostasis,but its involvement in other biological activities such as lowering hyperlipidemia,and diminishing insulin resistance has also been reported.In this study,we aimed to explore additional effects of adropin on oxidative stress,inflammation,and cell proliferation in an animal model of type 1 DM. Methods:To achieve our aim,normal and diabetic Wistar rats were treated with adropin(2.1μg/kg/day)for a period of 10days.Pancreatic tissue samples were collected for histo-morphological analysis and inflammation assay,while blood was collected for oxidative stress assay. Results:Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas,and adropin dramatically attenuated this effect in pancreatic exocrine tissue,but not in the islet of Langerhans.In addition,adropin signifi-cantly increased glutathione reductase expression in pancreatic tissue,and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats. Conclusion:Our study indicates the potential role of adropin in alleviating oxidative stress in DM.

摘要：Background:The precise insertion of large DNA fragments(＞3-5 kb)remains one of the key obstacles in establishment of genetically modified murine models. Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-hHRAS).Whole-genome se-quencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was veri-fied from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were con-ducted using hematoxylin and eosin(H&E)staining. Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202bp and 80625020bp.NF-hHRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100％of the NF-hHRAS transgenic mice developed tumors,with approximately 84％of male NF-hHRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NF-hHRAS mice,while the spontaneous tumor incidence remained low(1/50). Conclusions:The NF-hHRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).

摘要：As one of the most prevalent gastrointestinal malignancies in humans,gastric cancer(GC)is often detected at an advancedstage,resulting in a poor prognosis and ranking it the fifth leading cause of cancer-related deaths.Due to their high genomic correla-tion with humans,mice are ideal in vivo models for investigating GC-related patho-genesis and therapeutic interventions.This review provides an overview of different GC models,including genetically engineered,transplantation-based models,and chemically or biologically induced models,and discusses the recent advancements for each type,highlighting their unique contributions to the field.In addition,it summa-rizes the strengths,limitations,and typical applications of these models and offers a critical assessment of their applicability in research while acknowledging their current limitations in fully mirroring human GC progression.Furthermore,we analyze how each model accurately recapitulates the complexities of human GC and evaluate their potential for clinical translation.This review provides a reference for model selection in future GC research.