We have known for many years that the spinal cord can generate some basic locomotor outputs under specific experimental conditions without any input from the brain or the periphery（Stuart and Hultborn,2008）.However,...We have known for many years that the spinal cord can generate some basic locomotor outputs under specific experimental conditions without any input from the brain or the periphery（Stuart and Hultborn,2008）.However,when inputs from the brain are lost following spinal cord injury（SCI）,the mammalian spinal cord is unable to generate normal,goal-directed locomotor outputs.展开更多
Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represe...Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.展开更多
Objectives It is not fully clarified how diabetes mellitus induced cardiac dysfunction and myocardial ultrastructural changes in the early state.In the present study,we provided an integrated approach to investigate e...Objectives It is not fully clarified how diabetes mellitus induced cardiac dysfunction and myocardial ultrastructural changes in the early state.In the present study,we provided an integrated approach to investigate early changes in myocardial function of diabetic rabbits and assessed the structural alteration.Methods and Results Diabetes was induced by alloxan injection.After 30 days,echocardio- graphy and left ventricular cannulation were performed in dia- betic(D,n=8) and control rabbits(C,n= 10).After catheterization, animals were killed for histological studies.Hema-toxylin -eosin and Masson’s Trichrome staining of the heart were analyzed.The ultrastructure of left ventricle was also examined with electron microscopy.Echocardiography revealed that early diabetic cardiomyopathy had impaired LV diastolic function expressed by diminished E-waves,increased Awaves, E/A ratio reversion and increased E-wave deceleration time(EDT).Concurrently,LV end-diastolic pressure(LVEDP) and diastolic time constant(T) were increased,minimum dP/ dt(LV-dp/dt)was reduced,obtained through cardiac catheterization.There were no significant differences in LV ejection fraction(EF),LV peak systolic pressure(LVSP), or maximum dP/dt(LV + dp/dt).Qualitative light microscopy revealed no histologic changes in myocardium from diabetic rabbits.The most evident ultrastructural change was spotted myofibrillar damage,while interstitial fibrosis was slight.Conclusions These results suggest that early diabetic cardiomyopathy in animal model is characterized by left ventricular diastolic dysfunction,both impaired active relaxation and increased passive chamber stiffness.Whereas,left ventricular systolic function can remain normal.It might partly contribute to myofibrillar damage,but not myocardial fibrosis.展开更多
Based on 22 of the climate models from phase 3 of the Coupled Model Intercomparison Project, we investigate the ability of the models to reproduce the spatiotemporal features of the wintertime North Pacific Oscillatio...Based on 22 of the climate models from phase 3 of the Coupled Model Intercomparison Project, we investigate the ability of the models to reproduce the spatiotemporal features of the wintertime North Pacific Oscillation(NPO), which is the second most important factor determining the wintertime sea level pressure field in simulations of the pre-industrial control climate, and evaluate the NPO response to the future most reasonable global warming scenario(the A1B scenario). We reveal that while most models simulate the geographic distribution and amplitude of the NPO pattern satisfactorily, only 13 models capture both features well. However, the temporal variability of the simulated NPO could not be significantly correlated with the observations. Further analysis indicates the weakened NPO intensity for a scenario of strong global warming is attributable to the reduced lower-tropospheric baroclinicity at mid-latitudes, which is anticipated to disrupt large-scale and low-frequency atmospheric variability, resulting in the diminished transfer of energy to the NPO, together with its northward shift.展开更多
We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three int...We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.展开更多
Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantatio...Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantation were analyzed retrospectively. Seventy - four cases ( infection group) suffered serious infection,including 54 cases cured ( cure group) ,20 cases died (展开更多
Hypoxic pulmonary hypertension(HPH)is a pathophysiological state characterized by diverse clinical symptoms resulting from structural and functional changes in pulmonary vessels induced by hypoxic stimuli,leading to i...Hypoxic pulmonary hypertension(HPH)is a pathophysiological state characterized by diverse clinical symptoms resulting from structural and functional changes in pulmonary vessels induced by hypoxic stimuli,leading to increased pulmonary artery pressure.展开更多
We establish sharp functional inequalities for time-changed symmetric α-stable processes on Rd with d≥1 and α∈(0,2), which yield explicit criteria for the compactness of the associated semigroups. Furthermore, whe...We establish sharp functional inequalities for time-changed symmetric α-stable processes on Rd with d≥1 and α∈(0,2), which yield explicit criteria for the compactness of the associated semigroups. Furthermore, when the time change is defined via the special function W(x)=(1+|x|)β with β>α we obtain optimal Nash-type inequalities, which in turn give us optimal upper bounds for the density function of the associated semigroups.展开更多
We propose a nonparametric change point estimator in the distributions of a sequence of independent observations in terms of the test statistics given by Huˇskov′a and Meintanis(2006) that are based on weighted empi...We propose a nonparametric change point estimator in the distributions of a sequence of independent observations in terms of the test statistics given by Huˇskov′a and Meintanis(2006) that are based on weighted empirical characteristic functions. The weight function ω(t; a) under consideration includes the two weight functions from Huˇskov′a and Meintanis(2006) plus the weight function used by Matteson and James(2014),where a is a tuning parameter. Under the local alternative hypothesis, we establish the consistency, convergence rate, and asymptotic distribution of this change point estimator which is the maxima of a two-side Brownian motion with a drift. Since the performance of the change point estimator depends on a in use, we thus propose an algorithm for choosing an appropriate value of a, denoted by a_s which is also justified. Our simulation study shows that the change point estimate obtained by using a_s has a satisfactory performance. We also apply our method to a real dataset.展开更多
By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?...By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?11.7% in GroupⅠ (3 weeks after operation), and 78.4+ 11.6% in Group Ⅱ (3 months after operation). There were muscular atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P<0.05), but the difference between two groups was non?significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-esistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.展开更多
The endothelial function has been proven to be an important factor in the pathogenesis of atheroscle-rosis, hypertension and heart failure. The flow-mediated vasodilation (FMD) of the peripheral artery is an endotheli...The endothelial function has been proven to be an important factor in the pathogenesis of atheroscle-rosis, hypertension and heart failure. The flow-mediated vasodilation (FMD) of the peripheral artery is an endothelium-dependent function. Brachial-artery ultrasound scanning is the popular method for evaluat-ing FMD.展开更多
Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dy...Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.展开更多
The study of aging,particularly in the context of the gut,is a rapidly advancing field with significant implications for understanding the mechanisms underlying age-related diseases.The gut,as a major digestive and im...The study of aging,particularly in the context of the gut,is a rapidly advancing field with significant implications for understanding the mechanisms underlying age-related diseases.The gut,as a major digestive and immune organ,undergoes notable functional and structural changes with age.These changes include impaired nutrient absorption,altered gut microbiota,increased permeability,and heightened inflammation.Such disruptions can contribute to various age-associated pathologies,including metabolic disorders and inflammatory diseases(Calleja-Conde et al.2021).Investigating the molecular and genetic underpinnings of gut aging is crucial for identifying potential therapeutic targets that could ameliorate age-related declines in gut function and overall health.The study by Sun et al.(2024)contributes to this understanding by examining the role of Lipase H(Liph)and its Drosophila ortholog,CG6295,in gut aging,revealing novel insights into how lipid metabolism influences intestinal health and lifespan.展开更多
Epigenetics refers to heritable changes in gene function that occur without alterations to the DNA sequence.Major epigenetic mechanisms include DNA methylation,histone modifications,chromatin remodeling,and the regula...Epigenetics refers to heritable changes in gene function that occur without alterations to the DNA sequence.Major epigenetic mechanisms include DNA methylation,histone modifications,chromatin remodeling,and the regulatory ac-tions of small RNAs and long noncoding RNAs(Allis and Jenuwein,2016).These layers of regulation are essential for modulating gene expression and are widely involved in the regulation of plant growth and development,as well as in responses to environmental cues(Hemenway and Gehring,2023).展开更多
Objective： To explore the effect of Jisuikang （脊髓康, JSK） on kinetic dysfunction in patients after spinal injury. Methods： Eighty-four patients with spinal injury were assigned equally, according to a randomizin...Objective： To explore the effect of Jisuikang （脊髓康, JSK） on kinetic dysfunction in patients after spinal injury. Methods： Eighty-four patients with spinal injury were assigned equally, according to a randomizing digital table to the treated group and the control group. Conventional treatment was given to both groups, and JSK was additionally given to the treated group. Changes of various kinetic function concerning parameters including kinetic score, grades of spinal injury, effectiveness of the treatment and available recovery rate in patients allocated in the treated group and the control group were observed and compared in the way issued by Association of Spinal Injury of America （ASIA）. Results： Better effects were shown in the treated group than those in the control group in improving kinetic score （92.00 ± 9.95 scores vs 83.76 ± 24.12 scores）, ASIA overall improvement rate （69.05% vs 45.24%） and grades of effectiveness （P〈0.05）. However, the difference of available recovery rate between the two groups was insignificant （P〉0.05）. Cenclusien： JSK could prevent secondary alteration of spinal injury, promote the recovery and regeneration of nerve tissues, but could not restore the function of a necrotic spine.展开更多
文摘We have known for many years that the spinal cord can generate some basic locomotor outputs under specific experimental conditions without any input from the brain or the periphery（Stuart and Hultborn,2008）.However,when inputs from the brain are lost following spinal cord injury（SCI）,the mammalian spinal cord is unable to generate normal,goal-directed locomotor outputs.
基金supported by the National Key Programme of Research and Development,Ministry of Science and Technology of China(2022YFF1301600)National Natural Science Foundation of China(32030011,U24A20362,32070409)+2 种基金PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2021 GD0805)Qing Lan Project of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.
文摘Objectives It is not fully clarified how diabetes mellitus induced cardiac dysfunction and myocardial ultrastructural changes in the early state.In the present study,we provided an integrated approach to investigate early changes in myocardial function of diabetic rabbits and assessed the structural alteration.Methods and Results Diabetes was induced by alloxan injection.After 30 days,echocardio- graphy and left ventricular cannulation were performed in dia- betic(D,n=8) and control rabbits(C,n= 10).After catheterization, animals were killed for histological studies.Hema-toxylin -eosin and Masson’s Trichrome staining of the heart were analyzed.The ultrastructure of left ventricle was also examined with electron microscopy.Echocardiography revealed that early diabetic cardiomyopathy had impaired LV diastolic function expressed by diminished E-waves,increased Awaves, E/A ratio reversion and increased E-wave deceleration time(EDT).Concurrently,LV end-diastolic pressure(LVEDP) and diastolic time constant(T) were increased,minimum dP/ dt(LV-dp/dt)was reduced,obtained through cardiac catheterization.There were no significant differences in LV ejection fraction(EF),LV peak systolic pressure(LVSP), or maximum dP/dt(LV + dp/dt).Qualitative light microscopy revealed no histologic changes in myocardium from diabetic rabbits.The most evident ultrastructural change was spotted myofibrillar damage,while interstitial fibrosis was slight.Conclusions These results suggest that early diabetic cardiomyopathy in animal model is characterized by left ventricular diastolic dysfunction,both impaired active relaxation and increased passive chamber stiffness.Whereas,left ventricular systolic function can remain normal.It might partly contribute to myofibrillar damage,but not myocardial fibrosis.
基金Supported by the China National Global Change Major Research Project(No.2013CB956201)the National Science Foundation of China(NSFC)Key Project(No.41130859)+1 种基金the NSFC(Nos.41506009,41521091)the NSFC Major Project(No.41490643)
文摘Based on 22 of the climate models from phase 3 of the Coupled Model Intercomparison Project, we investigate the ability of the models to reproduce the spatiotemporal features of the wintertime North Pacific Oscillation(NPO), which is the second most important factor determining the wintertime sea level pressure field in simulations of the pre-industrial control climate, and evaluate the NPO response to the future most reasonable global warming scenario(the A1B scenario). We reveal that while most models simulate the geographic distribution and amplitude of the NPO pattern satisfactorily, only 13 models capture both features well. However, the temporal variability of the simulated NPO could not be significantly correlated with the observations. Further analysis indicates the weakened NPO intensity for a scenario of strong global warming is attributable to the reduced lower-tropospheric baroclinicity at mid-latitudes, which is anticipated to disrupt large-scale and low-frequency atmospheric variability, resulting in the diminished transfer of energy to the NPO, together with its northward shift.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11247010,11175055,11475053 and 11347017the Natural Science Foundation of Hebei Province under Grant Nos C2012202079 and C201400305
文摘We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.
文摘Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantation were analyzed retrospectively. Seventy - four cases ( infection group) suffered serious infection,including 54 cases cured ( cure group) ,20 cases died (
基金supported by General Program of the Natural Science Foundation of Hebei Province(No.H2024110033,China).
文摘Hypoxic pulmonary hypertension(HPH)is a pathophysiological state characterized by diverse clinical symptoms resulting from structural and functional changes in pulmonary vessels induced by hypoxic stimuli,leading to increased pulmonary artery pressure.
文摘We establish sharp functional inequalities for time-changed symmetric α-stable processes on Rd with d≥1 and α∈(0,2), which yield explicit criteria for the compactness of the associated semigroups. Furthermore, when the time change is defined via the special function W(x)=(1+|x|)β with β>α we obtain optimal Nash-type inequalities, which in turn give us optimal upper bounds for the density function of the associated semigroups.
基金supported by Natural Sciences and the Engineering Research Council of Canada (Grant No. 105557-2012)National Natural Science Foundation for Young Scientists of China (Grant No. 11201108)+1 种基金the National Statistical Research Plan Project (Grant No. 2012LZ009)the Humanities and Social Sciences Project from Ministry of Education of China (Grant No. 12YJC910007)
文摘We propose a nonparametric change point estimator in the distributions of a sequence of independent observations in terms of the test statistics given by Huˇskov′a and Meintanis(2006) that are based on weighted empirical characteristic functions. The weight function ω(t; a) under consideration includes the two weight functions from Huˇskov′a and Meintanis(2006) plus the weight function used by Matteson and James(2014),where a is a tuning parameter. Under the local alternative hypothesis, we establish the consistency, convergence rate, and asymptotic distribution of this change point estimator which is the maxima of a two-side Brownian motion with a drift. Since the performance of the change point estimator depends on a in use, we thus propose an algorithm for choosing an appropriate value of a, denoted by a_s which is also justified. Our simulation study shows that the change point estimate obtained by using a_s has a satisfactory performance. We also apply our method to a real dataset.
文摘By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?11.7% in GroupⅠ (3 weeks after operation), and 78.4+ 11.6% in Group Ⅱ (3 months after operation). There were muscular atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P<0.05), but the difference between two groups was non?significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-esistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.
文摘The endothelial function has been proven to be an important factor in the pathogenesis of atheroscle-rosis, hypertension and heart failure. The flow-mediated vasodilation (FMD) of the peripheral artery is an endothelium-dependent function. Brachial-artery ultrasound scanning is the popular method for evaluat-ing FMD.
基金supported by the National Natural Science Foundation of China(Nos.82300561,82270523,and 82305006)the Natural Science Foundation of Chongqing(No.CSTB2023NSCQ-MSX0713)+5 种基金the Chongqing Medical Young Talents Program(No.YXQN202452 and No.YXQN202415)the High-Level Military Technological Innovation Talent Program,the Chongqing Talent Program:Innovative Leading Talents(No.CSTC2024YCJH-BGZXM0011)the Sprint Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025CCXM-001)the Youth Program of Joint Medical Research of Chongqing Science and Chongqing Health Commission(No.2025QNXM038)the Special Funding for Postdoctoral Research Projects in Chongqing,the Science Foundation of State Key Laboratory of Trauma and Chemical Poisoning(No.2024K003)the Chongqing Natural Science Foundation Innovation and Development Joint Fund(Chongqing Education Commission)(No.CSTB2024NSCQLZX0079).
文摘Ischemic/hypoxic injury significantly damages vascular function,detrimentally impacting patient outcomes.Changes in mitochondrial structure and function are closely associated with ischemia/hypoxia-induced vascular dysfunction.The mechanism of this process remains elusive.Using rat models of ischemia and hypoxic vascular smooth muscle cells(VSMCs),we combined transmission electron microscopy,super-resolution microscopy,and metabolic analysis to analyze the structure and function change of mitochondrial cristae.Multi-omics approaches revealed arginase 1(Arg1)upregulation in ischemic VSMCs,confirmed by in vivo and in vitro knockout models showing Arg1's protective effects on mitochondrial cristae,mitochondrial and vascular function,and limited the release of mtDNA.Mechanistically,Arg1 interacting with Mic1o led to mitochondrial cristae remodeling,together with hypoxia-induced VDAC1 lactylation resulting in the opening of MPTP and release of mtDNA of VSMCs.The released mtDNA led to PANoptosis of VSMCs via activation of the cGAS-STING pathway.ChIP-qPCR results demonstrated that lactatemediated Arg1 up-regulation was due to H3K18la upregulation.VSMCs targeted nano-material PLGA-PEl-siRNA@PM-a-SMA(NPsiArg1)significantly improved vascular dysfunction.This study uncovers a new mechanism of vascular dysfunction following ischemic/hypoxic injury:a damaging positive feedback loop mediated by lactate-regulated Arg1 expression between the nucleus and mitochondria,leading to mitochondria cristae disorder and mtDNA release,culminating in VSMCs PANoptosis.Targeting VSMCs Arg1 inhibition offers a potential therapeutic strategy to alleviate ischemia/hypoxia-induced vascular impairments.
基金the National Key R&D Program of China(2023YFC3603300)the National Natural Science Foundation of China(82171558)+1 种基金Yunnan Fundamental Research Projects(202305AH340006,202201AS070038)the Pioneer Hundred Talents Program of the Chinese Academy of Sciences and the Yunnan Revitalization Talent Support Program Young Talent Project.
文摘The study of aging,particularly in the context of the gut,is a rapidly advancing field with significant implications for understanding the mechanisms underlying age-related diseases.The gut,as a major digestive and immune organ,undergoes notable functional and structural changes with age.These changes include impaired nutrient absorption,altered gut microbiota,increased permeability,and heightened inflammation.Such disruptions can contribute to various age-associated pathologies,including metabolic disorders and inflammatory diseases(Calleja-Conde et al.2021).Investigating the molecular and genetic underpinnings of gut aging is crucial for identifying potential therapeutic targets that could ameliorate age-related declines in gut function and overall health.The study by Sun et al.(2024)contributes to this understanding by examining the role of Lipase H(Liph)and its Drosophila ortholog,CG6295,in gut aging,revealing novel insights into how lipid metabolism influences intestinal health and lifespan.
基金supported by the National Natural Science Foundation of China(32230005).
文摘Epigenetics refers to heritable changes in gene function that occur without alterations to the DNA sequence.Major epigenetic mechanisms include DNA methylation,histone modifications,chromatin remodeling,and the regulatory ac-tions of small RNAs and long noncoding RNAs(Allis and Jenuwein,2016).These layers of regulation are essential for modulating gene expression and are widely involved in the regulation of plant growth and development,as well as in responses to environmental cues(Hemenway and Gehring,2023).
文摘Objective： To explore the effect of Jisuikang （脊髓康, JSK） on kinetic dysfunction in patients after spinal injury. Methods： Eighty-four patients with spinal injury were assigned equally, according to a randomizing digital table to the treated group and the control group. Conventional treatment was given to both groups, and JSK was additionally given to the treated group. Changes of various kinetic function concerning parameters including kinetic score, grades of spinal injury, effectiveness of the treatment and available recovery rate in patients allocated in the treated group and the control group were observed and compared in the way issued by Association of Spinal Injury of America （ASIA）. Results： Better effects were shown in the treated group than those in the control group in improving kinetic score （92.00 ± 9.95 scores vs 83.76 ± 24.12 scores）, ASIA overall improvement rate （69.05% vs 45.24%） and grades of effectiveness （P〈0.05）. However, the difference of available recovery rate between the two groups was insignificant （P〉0.05）. Cenclusien： JSK could prevent secondary alteration of spinal injury, promote the recovery and regeneration of nerve tissues, but could not restore the function of a necrotic spine.
