摘要：Background:The Vietnamese swine represents a promising animal model due to its anatomical,physiological,and pathophysiological similarities to humans.Notably,the arrangement of lobes and ducts in the mammary glands is highly comparable to that of humans and is histologically indistinguishable.Leveraging these advantages through the chemical induction of carcinogenesis in this model offers a robust approach to mimic human exposure to carcinogenic compounds. Methods:This study elaborates on a protocol for developing a representative model of MNU-induced invasive breast carcinoma in three Vietnamese swine,validated histologically and immunologically.It evaluates not only the tissue similarity with humans,but also the development of chemically induced mammary tumors in an im-munologically competent animal.Moreover,this study addresses the existing gap in histological knowledge regarding mammary tissue in the porcine model. Results:Our findings suggest that this model encompasses the full spectrum of can-cer.It incorporates the key elements of a tumor microenvironment that enable tumor growth and propagation,such as immune cells,blood vessels,fibroblasts,extracellular matrix,fatty acids,and signaling molecules. Conclusions:This model offers significant potential to advance the understanding of cancer pathogenesis and facilitate the development of innovative therapeutic strate-gies by closely replicating human tumor biology.

摘要：Background:Allergic rhinitis(AR)is a kind of immune disease mediated by IgE.We are intrigued by the potential role of DEK proto-oncogene(DEK)in inflammation-related diseases.We investigated the effects and mechanisms of DEK in treating AR,aiming to identify potential new treatment targets for AR. Methods:The AR mouse model was induced by house dust mite(HDM)(1mg/mL).HNEpCs stimulated by HDM(1mg/mL)were pretreated for 24h with or without DEK lentivirus.The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting,ELISA,flow cytometry,real-time quan-titative PCR,immunohistochemistry,HE staining,PAS staining,Diff staining,and immunofluorescence. Results:After DEK knockdown,the inflammatory response of AR mice was reduced.In addition,DEK deletion mitigated nasal tissue damage and mitochondrial division.Our further studies showed that DEK deletion or inhibition led to the down-regulation of RhoA activity and decreased phosphorylation of Ezrin and Drp1 proteins,and inhib-ited mitochondrial division.Overall,DEK deficiency mitigated AR by down-regulating RhoA/Ezrin/Drp1 pathway activity. Conclusion:DEK alleviates AR through RhoA/Ezrin/Drp1 signaling pathway,which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.

摘要：Background:The investigation of ovarian development,dysfunction,and aging is essential for female reproductive health.Despite extensive research on the cellular functions of Brefeldin A(BFA)as an intracellular transport inhibitor,its specific effects and mechanisms on ovarian development/aging remain inadequately understood. Methods:Mice and porcine oocytes/granulosa cells(GCs)were treated with BFA.Morphological and omics analyses(including Western blot,real-time polymerase chain reaction(RT-PCR),transcriptomics,and metabolomics)were conducted. Results:In 3-week-old female mice,BFA treatment significantly suppressed oocyte maturation,induced apoptosis,and increased estradiol and LH levels.This treatment upregulated apoptosis-related genes while downregulating proliferation-associated genes.Additionally,BFA elevated senescence markers(p21 and p26)and decreased the activity of the longevity gene SIRT6.In porcine oocytes,BFA reduced the maturation rate and lowered mRNA levels of key maturation-related genes,LHX8 and GDF9.In porcine GCs,BFA increased apoptosis and upregulated genes such as Caspase-3,BAX,and P21,while downregulating genes associated with proliferation and longevity.Similar effects were observed in 12-month-old female mice,indicating consistency across age groups.Metabolomic analysis in these mice revealed that BFA primarily impacted pathways related to steroid biosynthesis,ovarian steroidogenesis,and estrogen signaling.Transcriptomic analysis in 12-month-old female mice further demonstrated that BFA disrupted ovarian function through multiple mechanisms,including modulation of the GnRH signaling pathway,activation of the FOXO pathway,and interference with meiosis-related gene expression. Conclusion:Our findings are pivotal for advancing the understanding of ovarian aging,dysfunctions,and diseases,and ultimately facilitate addressing BFA's potential adverse effects on reproductive health/aging.

摘要：Xenotransplantation,that is,the transplantation of cells,tissues,and organs between species,is a rapidly developing alternative to classical transplantology in human medicine.Since the first successful kidney transplant in 1954,transplant medicine has made enormous progress.Until today,there are numerous patients worldwide waiting for an organ to be transplanted,and the number is still increasing,whereas the number of available organs is decreasing.One promising solution to this critical issue is the breeding of genetically modified animals as potential donors,which has gained the attention of scientists over the past two decades.Recent advancements in xenotransplantation have led to successful transfers of genetically modified pig organs into human recipients.Particularly,pig kidneys have been transplanted into living humans,demonstrating normal postsurgical function.Additionally,pig lungs functioned for 9 days in a brain-dead individual without experiencing hyperacute rejection.Furthermore,the successful xenotransplantation of pig hearts into living persons,exhibiting life-sustaining graft function,underscores significant progress toward clinically viable xenotransplants.This review provides an updated overview of the animal species and models used in xenotransplantation,with particular emphasis on the potential of transgenic pigs as donors.It discusses the process involved in producing the aforementioned animals,including the methods used to modify their genome.Particular attention is paid to immunological and genetic barriers,as well as zoonotic risks,and the possibilities and limitations of this technology.Although xenotransplantation is still in its experimental stage,it may play a crucial role in saving patients' lives in the future.

摘要：Background:Although widely used,the rat model remains poorly transferable to hu-mans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little used due to the lack of available literature.The aim of this article is to demonstrate the feasibility and effec-tiveness of an electrophysiological protocol combined with a motor function assess-ment to analyze nerve repair. Methods:Ten white New Zealand rabbits underwent a 4 cm transection of the fibular nerve.Autograft regeneration over 36 weeks was compared to non-repaired controls.The compound muscle action potential(CMAP)was recorded in the tibialis anterior and the extensor digitorum brevis.An electromyogram(EMG)was obtained after nee-dle insertion and resting muscle activity recording.The electrophysiological results were compared to the toe spread index(TSI),which assesses the motor functional recovery promoted by fibular nerve regeneration. Results:The autograft group regeneration starts between weeks 18 and 21 and nor-mal EMG was observed around the 30th week.These electrophysiological results were compared to the well-defined toe spread reflex.This motor test showed a sig-nificant functional return of 59％at 36 weeks(p＜0.05).Rabbits regain nearly 80％of their muscle mass. Conclusion:Nerve conduction allows detection of nerve regeneration of the mus-cle while electromyography indicates when muscle activity returns to normal.These studies are reliable and non-invasive techniques to evaluate fibular nerve regenera-tion in the rabbit's hindlimb.Nonetheless,it is necessary to have qualified personnel,since inter-manipulator variations have been observed.

摘要：Radiological or nuclear accidents can lead to serious outcomes for individuals exposed to ionizing radiation,with health effects that are either acute or delayed,deterministic or stochastic,depending on the effective dose of exposure.Mechanistically,ionizing radiation can inflict damage either directly on DNA or through oxidative stress,which may trigger a cascade of damages to tissues and organs.The development of effec-tive radiation medical countermeasures is an unmet need and should be a top priority in preparing for radiation emergencies.This paper aims to address the critical ques-tions of whether current countermeasures are available,what additional measures are needed,and what actions can be taken to enhance the development of radiation medical countermeasures from a systematic perspective.

摘要：Background:Ketamine is a widely used anesthetic in animal research,but its use is strictly regulated in several countries,including Japan and China.As an alternative,the medetomidine-midazolam-butorphanol(MMB)combination is commonly used in Japan.However,medetomidine is a racemic mixture containing the inactive R-enantiomer,which may reduce anesthetic predictability and safety. Objective:The aim of the study was to evaluate the efficacy and safety of a modified anesthetic combination(dMMB),in which dexmedetomidine replaces medetomidine,across three commonly used mouse strains(ICR,C57BL/6,BALB/c). Methods:Male and female mice were administered either MMB or dMMB sub-cutaneously.Anesthetic depth,recovery profiles,heart rate,SpO2,body temper-ature,ocular opacity,and blood glucose levels were assessed.Atipamezole was used to reverse anesthesia,and thermoregulatory recovery was monitored postinjection. Results:dMMB produced similar anesthetic depth to MMB,with faster and more con-sistent recovery,particularly in males.Body temperature recovery was significantly enhanced in dMMB-treated B6 males.No significant differences in side effects(ocu-lar opacity or blood glucose levels)were observed between protocols,though strain-specific glucose elevations were noted in dMMB-treated males. Conclusion:dMMB is a safe,effective,and ketamine-free injectable anesthetic pro-tocol,offering advantages in recovery and thermoregulation.It may be a valuable alternative in research settings where ketamine is restricted and medetomidine may become unavailable.

摘要：Background:Endoplasmic reticulum(ER)stress is an important factor in the develop-ment of numerous cardiovascular disorders;nevertheless,the association between ER stress and mitral regurgitation(MR)remains inadequately characterized.The mo-lecular mechanism of pimobendan(PIMO)that contributes to the delay in congestive heart failure(CHF)in MR associated with apoptosis and fibrosis is still unclear.Our aim was to examine the impact of PIMO on ER stress,apoptosis,and fibrosis in a chronic MR rat model. Methods:MR was surgically induced in 10 Sprague-Dawley rats,with 5 serving as sham operation controls.At 8weeks postsurgery,the MR animals were randomly al-located into two groups:MR and MR+PIMO groups.PIMO was administered twice daily through oral gavage for 4weeks,whereas the sham and MR groups were ad-ministered similar quantities of drinking water.Echocardiography was conducted be-fore the delivery of PIMO as a baseline measure and at the end of the study.At the end of the investigation,hearts were procured for histopathological and ER stress evaluations. Results:PI MO significantly maintained heart function and structural remodeling in the MR animals.PIMO significantly reduced MR-induced myocyte apoptosis(p=0.044)and fibrosis(p=0.002)by reducing the messenger RNA expression of genes associ-ated with ER stress(GRP78[glucose-regulated protein 78],ATF4[activating transcrip-tion factor 4],and CHOP[C/ERP homologous protein])compared to the MR group(p＜0.05,p＜0.01,and p＜0.001,respectively). Conclusion:PIMO demonstrated cardioprotective benefits on heart function,myo-cyte apoptosis,and fibrosis by regulating ER stress in an MR-induced CHF rat model.

摘要：Background:Cancer-associated cardiac cachexia(CACC)refers to cardiac injury in cancer patients in a malignant state,but preclinical animal models remain inad-equately developed. Methods:This study established CACC models in C57BL/6J and BALB/c mice using orthotopic,intra-abdominal,and hematogenous metastatic tumor induction.Multimodal cardiac assessments,including echocardiography,transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis,and ex vivo car-diomyocyte contractility assays,were systematically applied. Results:Metastatic burden triggered CACC characterized by cardiac mass reduction,epicardial fat depletion,interstitial fibrosis,and electrocardiographic abnormalities.Histopathological analysis revealed cardiomyocyte atrophy,myofibrillar disarray,mitochondrial dysfunction,and ubiquitin-mediated Myh6 degradation via MuRF-1,accompanied by compensatory Myh7 upregulation.These findings mechanisti-cally link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion:This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy.Our integrated ap-proach delineates a hierarchical progression from subcellular dysfunction to macro-scopic cardiac deterioration.

摘要：Type 2 Diabetes(T2D)is a growing global health issue,often aggravated by excessive sugar intake.Chronic high-sucrose diets contribute to insulin resistance,oxidative stress,and pancreatic dysfunction,worsening metabolic health.Sodium-glucose co-transporter 2(SGLT2)inhibitors,like empagliflozin,show potential in improving glycemic control and metabolic parameters,but their effects on pancreatic efficiency in sugar-induced T2D are not well understood.This study aimed to explore the effects of empagliflozin on metabolic and pancreatic protection in a high-sucrose diet-induced T2D model.Male Wistar rats were divided into four groups:normal,normal-treated,diabetic,and diabetic-treated(n=8 per group).Diabetes was induced with a 35％sucrose solution for 8 weeks,followed by a low-dose streptozotocin(STZ)injection.Treated groups received empagliflozin(15 mg/kg/day)for the duration.Biochemical markers,including fasting blood sugar(FBS),lipid profile,insulin levels,and oxidative stress markers,were measured.Insulin resistance(HOMA-IR)and pancreatic function(HOMA-B)were assessed.Histological analysis of pancreatic tissues was performed.The high-sucrose diet increased FBS,insulin resistance,and oxidative stress,while decreasing pancreatic function and islet diameter.Empagliflozin treatment lowered FBS(p=0.001),improved insulin sensitivity(p=0.001),reduced triglycerides(p=0.001),and LDL(p=0.05).It also enhanced antioxidant enzymes,reduced lipid peroxidation(MDA,p=0.001),and preserved pancreatic islet structure(p=0.001).A high-sucrose diet negatively affects metabolic health and pancreatic function.Empagliflozin mitigates these effects by improving metabolism,reducing oxidative stress,and preserving pancreatic integrity,suggesting its potential as a therapeutic agent in diabetes related to excessive sugar consumption.

摘要：Vitamin D,with its diverse molecular pathways and immunomodulatory proper-ties,has become a crucial tool in the prevention and treatment of various cancers.It controls angiogenesis,apoptosis,differentiation,and cellular proliferation,inhibit-ing cancer through immune surveillance,DNA repair,and tumor suppression genes.Additionally,vitamin D signaling impacts tumor growth and metastasis in various cancer types by interacting with key oncogenic pathways like Wnt/β-catenin,NF-κB,PI3K/Akt,and p53.This review demonstrates the molecular and therapeutic implica-tions of vitamin D in oncology,focusing on its potential as a safe,adjuvant treatment method.It emphasizes the role of vitamin D in epigenetic modification,its impact on tumor microenvironment,and its synergistic benefits when combined with im-mune checkpoint inhibitors and chemotherapeutic drugs.Despite promising results,genetic variations in the VDR gene continue to cause issues with bioavailability,ideal dosage,and interindividual response variability.The review also proposes future re-search on vitamin D's potentiality as a therapeutic adjuvant in various malignancies,including colorectal,prostate,and breast cancers,and suggests the development of non-calcemic vitamin D analogs and the incorporation of vitamin D-based methods into personalized oncology treatments.

摘要：Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disor-der resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD. Methods:After PDX development,methylation array,whole exome sequencing,and NanoString techniques were applied to describe the genetic landscape of CMMRD. Results:A 61/2-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated me-dulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she re-mained free of disease progression.At 10years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dpHGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G＞A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dpHGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dpHGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 path-ogenic variants in the medulloblastoma,dpHGG,and PDX,respectively.Only the me-dulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors. Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.

摘要：Robust preclinical models of transgender male(TGM)gender-affirming hormone ther-apy(GAHT)can inform clinicians of the isolated effects of GAHT;however existing models vary significantly in approach.We aimed to assess existing methodology and how it influences circulating sex-hormone levels in rodent models of TGM GAHT to provide recommendations of best practise.PubMed,Embase,and Scopus databases were systematically searched for studies that investigated GAHT in rodent models and were published from inception to the 1st of August 2024.Study characteristics and methodology were extracted and compared.Post-intervention circulating sex hormone concentrations were the primary outcome used to determine whether suc-cessful gender affirming hormone therapy had been achieved.Sixteen experimental rodent studies were included.Studies were performed on mice(n=11)and rats(n=5).Subcutaneous(SC)pellets and SC silastic implants were featured in some studies but weekly SC injections of testosterone enanthate was the preferred method.Sesame oil was the preferred solvent for injected testosterone formulations.Weekly doses of～450μg(mice)and～420-900 μg(rats)consistently induced the testosterone levels of the male counterpart.Similarly,10mg of unesterified testosterone in a SC silastic implant in mice or 10mg/100g in rats were also successful methods.Most studies ad-ministered hormones for 6-8 weeks before performing post-treatment assessments.This review demonstrates that methods largely varied across studies and successfully identifies the effective methodological approaches that improve the reproducibility and accuracy of preclinical models.Representing an integral step forward to bridging gaps in preclinical transgender healthcare research.

摘要：Background:This study investigated the phenolic profile,antioxidant capacity,anti-bacterial effect,and antihemolytic activity of nettle leaves from two understudied Algerian species,Urtica pilulifera and Urtica urens. Methods:Urtica pilulifera and Urtica urens leaves extracts were prepared by maceration using methanol and distilled water respectively.Their phytochemical analysis(total phe-nolic content,flavonoids,hydrolysable and condensed tannins)was determined.The chemical profle of these extracts was performed using ultra-high-performance liquid chromatography diode array detection tandem mass spectrometry.Antioxidant activity(using the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method),antibacterial activity(using disk diffusion method),and antihemolytic activity were carried out. Results:Results reveal high levels of flavonoids,tannins,alkaloids,and terpenoids.Several classes of compounds were identified in the extracts.Phenolic acid and other acids and their derivatives and flavonoids were detected in the extracts,with 4-O-caffeoyl-quinic acid and 5-O-caffeoyl-quinic acid being the main constituents in both extracts.Caffeic acid was also the main constituent present only in U.urens extract.For antioxidant activity of the metha-nolic extract of U.pilulifera and the aqueous extract of U.urens,the percentage inhibition value(82.76％and 59.06％)and the half-maximum inhibitory concentration(IC50)value(302 and 423μg/mL),respectively,were obtained.Antibacterial activity of nettle extracts(10mg/mL)demonstrated the sensitivity of pathogenic strain susceptibility.The strongest antibacterial effect on tested strains was found in the aqueous extract of U.urens against Staphylococcus aureus(21±0.41mm)compared to the methanolic extract of U.pilulifera(16±0.40mm).The antihemolytic activity in the methanolic and aqueous extracts was 76.26％and 60.67％,re-spectively.The methanolic extract exhibited exceptional antihemolytic effect,with an IC50 value of 327μg/mL,whereas the aqueous extract had an IC50 value of 412μg/mL. Conclusions:The study confirms the presence of bioactive substances in the nettle species,including flavonoids and tannins,which possess antioxidant,antibacterial,and antihemolytic properties,and can be processed into food and pharmaceutical products.

摘要：Background:Maternal viral infection during pregnancy can lead to maternal immune activation(MIA),increasing the risk of neurodevelopmental disorders in offspring.Amantadine(AMA)exhibits antiviral activity and is widely employed in the manage-ment of neurologic conditions.Nevertheless,the efficacy of AMA in treating MIA is currently not established. Methods:MIA was induced by polyinosinic acid-polycytidylic acid(poly(I:C));AMA was administered from embryonic(E)day 11.5 for 3days.BV-2 cells were stimulated using poly(I:C)and treated with AMA.Behavior was assessed via open field test,elevated plus maze test,three-chamber sociability test,and marble burying test.Neuronal morphology was vizualized using Nissl stain;apoptosis via TUNEL(terminal deoxynucleotidyl transferase dUTP nick-end labeling)stain;protein expression(Iba1,NeuN,CD68,TNF-α[tumor necrosis factor-alpha],IL-1β[interleukin-1β])using immu-nofluorescence(IF);interleukin-6(IL-6)levels using enzyme-linked immunosorbent assay;reactive oxygen species using staining;Iba1,NeuN,Bcl-2,Bax,and cleaved caspase 3 using Western blot;and gene expression changes using RNA-seq. Results:AMA treatment reduced the levels of IL-6 in maternal blood,improved autism-like behaviors in MIA offspring,and effectively prevented neuronal damage and neuroinflammation.In vitro cellular studies have demonstrated that AMA effec-tively downregulates the expression levels of pro-inflammatory cytokines,including IL-6,TNF-α,and IL-1β.RNA-seq analysis indicated that AMA mitigates abnormal acti-vation of microglia by modulating inflammatory pathways associated with IL-6. Conclusion:AMA can prevent the development of neuropsychiatric disorders in MIA offspring.This effect may be related to its ability to attenuate neuronal damage,re-duce neuronal apoptosis,and inhibit neuroinflammation,indicating that the antiviral drug AMA may be a potential treatment for MIA.

摘要：Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the patho-genic mechanism of hypertension and examining new treatments.An optimal ani-mal model for studies on hypertension must well mimic human-like hemodynamics and pathophysiological structural modification,showing human disease features and complications timely or even ahead of time.A review of the most frequently used hypertensive animal models available,including small and large animals,induced and genetic models,would provide an insight into the appropriate targets to be addressed in the development of different hypertensive animal models.Another focus of the review are the processes of target-organs injury caused by high blood pressure,which mainly influences human health.

摘要：Background:Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics.Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy.Using an established baboon model of S.pneumoniae pneumonia,we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets. Methods:We performed whole blood transcriptomics,unbiased proteomics,and peripheral cytokine measurements serially in baboons inoculated with S.pneumoniae(n=23)or saline(n=10)and modeled the peripheral blood host response using principal components analysis and complex sparse logistic regression.Differentially expressed genes were analyzed for pathway analysis. Results:Inoculated animals developed characteristic signs and symptoms of pneumonia.A 39-gene signature was derived that classified S.pneumoniae infection with high accuracy(auROC 0.9 and 0.99 at 24 and 48h post-inoculation,respectively).Similar performance was observed for 48-h biomarker signatures derived from peripheral blood plasma proteomic and cytokine measurements(both auROC＞0.9).The gene signature retained strong diagnostic performance(auROC=0.88)when transformed to human orthologs and applied to patients with acute respiratory illness(n=34)or healthy controls(n=20).Pathway analysis at 48 h identified down-regulation of mitophagy and glucocorticoid signaling in peripheral blood. Conclusions:We report novel peripheral blood gene and protein expression signatures of S.pneumoniae pneumonia that could improve pneumonia diagnosis and found distinct pathways that may be amenable to modulation.Our findings illustrate how non-human primate models of bacterial pneumonia can successfully translate biomarker discoveries to patients.

摘要：In this study,we aimed to develop an in vivo electrophysiological bone-nerve prepa-ration to record the activity of peripheral sensory neurons that innervate the mu-rine tibia.A small nerve that innervates the tibial marrow cavity was identified in isoflurane-anesthetized C57BL/6 mice,and placed over a platinum hook electrode for extracellular recording.Whole-nerve activity was amplified,filtered and sampled at 20kHz using PowerLab(ADInstruments).A cannula was placed into the marrow cavity to deliver mechanical stimuli(by pressurizing with injection of saline)and/or capsaicin.Optical stimulation was achieved by application of 473 nm blue light(1 Hz,0.25-0.5 ms,0-12.5 mW/mm)to the tibial marrow cavity in Wnt1-Cre;IoxP-ChR2 mice.Murine bone afferent neurons responded to high threshold noxious mechanical stimulation,coded for the intensity of mechanical stimulation,could be sensitized by capsaicin,and did not suffer stimulus-evoked fatigue at 10-minute interstimulus inter-vals.Electrical and optical stimulation within the marrow cavity evoked action poten-tials with conduction velocities in the Aδ and/or C fiber range.These new approaches to recording the activity of bone afferent neurons will allow us to take advantage of transgenic and optogenetic tools to further our understanding of mechanisms that generate and maintain bone pain in the future.

摘要：Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine devel-opment due to their high mutation rates.Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses,whereas messenger RNA(mRNA)vaccines have demonstrated significant advantages due to their short development periods,straightforward production,and low costs.After the outbreak of the COVID-19 pandemic,multiple mRNA vaccines,including Pfizer-BioNTech and Moderna,rapidly received emergency use authorization,validating their feasibility.The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikó and Drew Weissman,underscoring the efficacy of mRNA vaccine technology.In 2024,the U.S.Food and Drug Administration(FDA)approval of Moderna's respiratory syn-cytial virus(RSV)mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation.This review article summarizes the design,clinical research,and future challenges of mRNA vaccines for respiratory viruses,delving into antigen design,mRNA delivery systems,and advancements in vaccines for multiple respira-tory viruses,including innovations in self-amplifying mRNA and circular mRNA vac-cines.Additionally,the development of combination vaccines is underway,aiming to provide protection against multiple viruses through a single administration.Despite the significant progress in mRNA vaccine development,challenges remain regarding raw material costs,stability,and delivery efficiency.In the future,with technologi-cal advancements and the accumulation of clinical experience,the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized,thereby enhancing their safety and efficacy.