Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
To investigate the differences in combustion and energy release characteristics of metastable intermolecular composite materials composed of aluminum alloys and polyvinylidene fluoride(PVDF)with different compositions...To investigate the differences in combustion and energy release characteristics of metastable intermolecular composite materials composed of aluminum alloys and polyvinylidene fluoride(PVDF)with different compositions,two types of alloys were selected:Al-Mg and Al-Si.Pure aluminum powder of the same size was also chosen for comparison.The PVDF-coated metal particle composites and the mixtures of PVDF with metal particles were prepared using electrospray(ES)and physical blending methods(PM),respectively.A systematic study was conducted on the morphology,compositional structure,combustion performance,energy release characteristics,and thermal reactivity of the fabricated composites and their combustion products through scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),X-ray diffraction(XRD),combustion performance experiments,closed vessel pressure tests,and simultaneous thermogravimetric-differential scanning calorimetry(TG-DSC).The experimental results indicated that the PVDF-coated metal particles prepared by the electrospray method exhibited a distinct core-shell structure,with the metal particles in close contact with the PVDF matrix.Compared to the PM blended materials,the ES composites demonstrated superior combustion performance and energy release characteristics during combustion.Analysis of different metal fuel systems under identical preparation conditions revealed that Al-Mg and Al-Si fuels modulate the combustion and energy release properties of aluminum alloy-PVDF MICs through two distinct pathways.展开更多
Objectives:To assess job satisfaction among anesthesia graduates working in various medical institutions across China.Methods:A cross-sectional survey was conducted,collecting demographic information,Minnesota Satisfa...Objectives:To assess job satisfaction among anesthesia graduates working in various medical institutions across China.Methods:A cross-sectional survey was conducted,collecting demographic information,Minnesota Satisfaction Questionnaire scores,work pressure,and turnover intentions.Multiple linear regression analysis was used to examine factors influencing job satisfaction.The electronic survey was distributed to Chinese anesthesia graduates from December 2021 to January 2022.Results:A total of 595 questionnaires were distributed,with 318 valid responses,resulting in a response rate of 53.4%.The participants’overall job satisfaction score on the Minnesota Satisfaction Questionnaire was 75.85±12.57.Multiple linear regression analysis identified the following variables as significantly associated with job satisfaction:age,daily working hours,income,current position,and work pressure.Conclusions:Anesthesia graduates in China reported slightly higher-than-average overall job satisfaction.However,several issues remain.Attention should be given to the impact of factors such as youth,long working hours,low income,current position,and high work pressure on job satisfaction.The government should support anesthesiologists with improved training,job security,and benefits to enhance job satisfaction.展开更多
Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cy...Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cytoskeletal reconstruction.However,it is unclear whether microtubule dynamics play a role in this process.To address this,we treated cultured sciatic nerve explants,an in vitro model of Wallerian degeneration,with the microtubule-targeting agents paclitaxel and nocodazole.We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation,whereas nocodazole-induced microtubule destabilization inhibited these processes.Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration,as well as functional recovery of nerve conduction and target muscle and motor behavior,respectively.These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration.This study was approved by the Animal Care and Use Committee of Southern Medical University,China(approval No.SMUL2015081) on October 15,2015.展开更多
Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensi...Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.展开更多
LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further...LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription （RT）-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 （CCK8）, colony-forming efficiency （CFE） and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H202-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes andspermatogenesis.展开更多
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金the National Natural Science Foundation of China(NSFC,Grant Nos.52176114 and 52306145)Natural Science Foundation of Jiangsu Province(Grant No.BK20230929)+3 种基金China Postdoctoral Science Foundation(Grant No.2023M731693)Fundamental Research Funds for the Central Universities,Grant No.30924010505Jiangsu Funding Program for Excellent Postdoctoral Talentthe Center of Analytical Facilities,Nanjing University of Science and Technology for providing technical equipment support for this article。
文摘To investigate the differences in combustion and energy release characteristics of metastable intermolecular composite materials composed of aluminum alloys and polyvinylidene fluoride(PVDF)with different compositions,two types of alloys were selected:Al-Mg and Al-Si.Pure aluminum powder of the same size was also chosen for comparison.The PVDF-coated metal particle composites and the mixtures of PVDF with metal particles were prepared using electrospray(ES)and physical blending methods(PM),respectively.A systematic study was conducted on the morphology,compositional structure,combustion performance,energy release characteristics,and thermal reactivity of the fabricated composites and their combustion products through scanning electron microscopy(SEM),energy-dispersive X-ray spectroscopy(EDS),X-ray diffraction(XRD),combustion performance experiments,closed vessel pressure tests,and simultaneous thermogravimetric-differential scanning calorimetry(TG-DSC).The experimental results indicated that the PVDF-coated metal particles prepared by the electrospray method exhibited a distinct core-shell structure,with the metal particles in close contact with the PVDF matrix.Compared to the PM blended materials,the ES composites demonstrated superior combustion performance and energy release characteristics during combustion.Analysis of different metal fuel systems under identical preparation conditions revealed that Al-Mg and Al-Si fuels modulate the combustion and energy release properties of aluminum alloy-PVDF MICs through two distinct pathways.
基金supported by the Basic Medical Research Foundation of Naval Medical University(2022SK029 and 2023QN035).
文摘Objectives:To assess job satisfaction among anesthesia graduates working in various medical institutions across China.Methods:A cross-sectional survey was conducted,collecting demographic information,Minnesota Satisfaction Questionnaire scores,work pressure,and turnover intentions.Multiple linear regression analysis was used to examine factors influencing job satisfaction.The electronic survey was distributed to Chinese anesthesia graduates from December 2021 to January 2022.Results:A total of 595 questionnaires were distributed,with 318 valid responses,resulting in a response rate of 53.4%.The participants’overall job satisfaction score on the Minnesota Satisfaction Questionnaire was 75.85±12.57.Multiple linear regression analysis identified the following variables as significantly associated with job satisfaction:age,daily working hours,income,current position,and work pressure.Conclusions:Anesthesia graduates in China reported slightly higher-than-average overall job satisfaction.However,several issues remain.Attention should be given to the impact of factors such as youth,long working hours,low income,current position,and high work pressure on job satisfaction.The government should support anesthesiologists with improved training,job security,and benefits to enhance job satisfaction.
基金supported by the National Natural Science Foundation of China,Nos.82071386 (to JS),81870982 (to JS)&81571182 (to JS)the National Key Basic Research Program of China,No.2014CB542202 (to JS)+3 种基金the Program for Changjiang Scholars and Innovative Research Team in University of China,No.IRT-16R37 (to JS)Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR110104008 (to HZ)Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China,No.N201904 (to JS)Natural Science Foundation of Guangdong Province of China,No.2017A030312009 (to JS)。
文摘Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cytoskeletal reconstruction.However,it is unclear whether microtubule dynamics play a role in this process.To address this,we treated cultured sciatic nerve explants,an in vitro model of Wallerian degeneration,with the microtubule-targeting agents paclitaxel and nocodazole.We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation,whereas nocodazole-induced microtubule destabilization inhibited these processes.Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration,as well as functional recovery of nerve conduction and target muscle and motor behavior,respectively.These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration.This study was approved by the Animal Care and Use Committee of Southern Medical University,China(approval No.SMUL2015081) on October 15,2015.
基金supported by CAMS Innovation Fund for Medical Sciences(Grant No.:2019-I2M-5e020)the National Natural Science Foundation of China(Grant No.:81503154)the National Major Scientific and Technological Special Project for Significant New Drugs Development(Grant No.:2017ZX09101002-001-005).
文摘Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
文摘LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription （RT）-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 （CCK8）, colony-forming efficiency （CFE） and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H202-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes andspermatogenesis.
