By means of the Penn State-NCAR Mesoscale Model Version 5(MM5)with a horizontal resolution of 20 km.the maintainable mechanism of Meso-β scale Convective System(Mβ CS)has been investigated on the basis of simulation...By means of the Penn State-NCAR Mesoscale Model Version 5(MM5)with a horizontal resolution of 20 km.the maintainable mechanism of Meso-β scale Convective System(Mβ CS)has been investigated on the basis of simulation of the temporal and spatial thermodynamics structure of the MβCS which occurred in Wuhan and its surroundings on 21 July 1998.The occurrence of the significant warm-core in the center of the MβCS happened in Changjiang River Basin between the Mufu Mountain and the Dabie Mountain.To the southern side of the MβCS,there exist the southwest low-level jet(LLJ)and the vertical secondary circulation in the low and middle troposphere respectively.In respect to the northern of the MβCS,the northwest jet emerges in the upper troposphere,accompanied with cold and dry atmosphere downdrafts,resulting in another secondary circulation.The foregoing mentioned vertical wind shear provides a favorable dynamical environment for the intensification and maintenance of the MβCS.Equally important,the latent heat release associated with the MβCS produces the warm center in the middle troposphere and the pressure falls.The pressure drop then accelerates air parcels toward the low leading to strong convergence as well as the intensified convection,establishing a positive feedback between the convection and the latent heat release,which is the thermodynamic mechanism of the development and maintenance of the MβCS.展开更多
Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playin...Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.展开更多
Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are...Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self...Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive.In this study,we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes.Genetically overexpressing PTEN-induced putative kinase 1(PINK1)protects against cartilage degeneration by removing defective mitochondria.PINK1 knockout aggravated cartilage damage due to impaired mitophagy.SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism.Specifically,PINK1 phosphorylated PKM2 at the Ser127 site,preserving its active tetrameric form.This inhibited nuclear translocation and the interaction withβ-catenin,resulting in a metabolic shift and increased energy production.Finally,a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguarding the structural integrity of articular joints and improving motor functions.Overall,this study provides a novel insight into the regulation of mitochondrial renewal and metabolic switches in OA.展开更多
1. Introduction Prognostics, known as ‘Remaining Useful Life(RUL) prediction', plays a crucial role in health management of critical systems, which is vital for maintaining the operating safety and reliability, a...1. Introduction Prognostics, known as ‘Remaining Useful Life(RUL) prediction', plays a crucial role in health management of critical systems, which is vital for maintaining the operating safety and reliability, and reducing the management costs.1Here, the RUL is usually defined as the length from the current time to the end of the useful life.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflamm...Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.展开更多
Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental...Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.展开更多
Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE pr...Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.展开更多
Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and ...Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.展开更多
As 2024 comes to an end,the pickup in consumption and robust growth in a range of sectors have bolstered confidence that the Chinese economy is right on track to meet the preset growth rate of around five percent.Bene...As 2024 comes to an end,the pickup in consumption and robust growth in a range of sectors have bolstered confidence that the Chinese economy is right on track to meet the preset growth rate of around five percent.Benefiting from a flurry of consumption-stimulating policies and measures,China’s online retail sales surpassed RMB 14 trillion in the January-November period,a year-on-year increase of 7.4 percent.Imports and exports maintained steady growth,climbing by 4.9 percent year-on-year in renminbi terms.Value-added industrial output also expanded 5.8 percent year-on-year.The volume of express delivery parcels reached a new high of 150 billion and is expected to grow higher still given the new-year festivities ahead.展开更多
In life,we are bound to encounter various difficulties and setbacks.However,it is of great significance to maintain a positive attitude when were facing these challenges.For me,this lesson was deeply impressed upon me...In life,we are bound to encounter various difficulties and setbacks.However,it is of great significance to maintain a positive attitude when were facing these challenges.For me,this lesson was deeply impressed upon me during a particularly tough period.展开更多
If you are to choose an event that can best represent China’s culture,undoubtedly,it will be the Spring Festival,or the Chinese Lunar New Year.It is a cherished occasion for families to get together,extend best wishe...If you are to choose an event that can best represent China’s culture,undoubtedly,it will be the Spring Festival,or the Chinese Lunar New Year.It is a cherished occasion for families to get together,extend best wishes to the people around them,and maintain friendships.展开更多
China’s economy is expected to remain stable throughout 2025.According to projections by the Center for Forecasting Science of the Academy of Mathematics and Systems Science under the Chinese Academy of Sciences,Chin...China’s economy is expected to remain stable throughout 2025.According to projections by the Center for Forecasting Science of the Academy of Mathematics and Systems Science under the Chinese Academy of Sciences,China’s GDP(gross domestic product)growth should settle at around 4.8 percent this year and will likely hit 5 percent if the government’s stimulus package is effectively implemented.I personally believe that the Chinese economy will maintain growth of about 4.6 percent in 2025 with robust performance in the first and fourth quarters and slower economic activity in the second and third quarters.展开更多
The annual Central Economic Work Conference 2024,held on December 11-12,set the overall goal and policy framework for Chinese economy in 2025,a crucial year in China’s economic development as the final year of the 14...The annual Central Economic Work Conference 2024,held on December 11-12,set the overall goal and policy framework for Chinese economy in 2025,a crucial year in China’s economic development as the final year of the 14th Five-Year Plan(FYP)and the preparation for the 15th FYP.A series of incremental fiscal and monetary policies adopted since the end of September has seen their initial effects in stabilizing stock markets and boosting consumption and production and thus enhanced the confidence of meeting the GDP goal for 2024.In the face of complicated external challenges and domestic difficulties-inadequate effective demand,overcapacity in some sectors and weak expectations,it is crucial to maintain stable growth in 2025.The Central Economic Work Conference 2024 set the general goal of 2025 on maintaining stable growth,employment and consumer prices.展开更多
China-Africa relations maintained their upward trajectory in 2024,with new plans for future cooperation taking shape.Chinese President Xi Jinping described the China-Africa partnership as being at its best in history....China-Africa relations maintained their upward trajectory in 2024,with new plans for future cooperation taking shape.Chinese President Xi Jinping described the China-Africa partnership as being at its best in history.The Beijing Summit of the Forum on China-Africa Cooperation(FOCAC),held in September 2024,elevated bilateral ties between China and African countries with diplomatic relations with China to a strategic level.It also redefined China-Africa relations as an“all-weather China-Africa community with a shared future for the new era.”This signifies that China and Africa will remain steadfast friends and close development partners,regardless of changes in the international landscape.展开更多
The year 2025 marks the 45th anniversary of the establishment of diplomatic relations between China and Zimbabwe.During this period,China-Zimbabwe economic cooperation has deepened,especially in the fields of infrastr...The year 2025 marks the 45th anniversary of the establishment of diplomatic relations between China and Zimbabwe.During this period,China-Zimbabwe economic cooperation has deepened,especially in the fields of infrastructure construction,mineral resource development,and agriculture.The two sides have maintained a high degree of political mutual trust and have cooperated closely in international affairs.Cultural exchanges and people-to-people contacts have expanded,and both nations continue to work together to further deepen their partnership.展开更多
Resilience has emerged as a critical concept in nursing research,offering a lens through which to understand how individuals,families,and communities navigate adversity,maintain well-being,and thrive in the face of ch...Resilience has emerged as a critical concept in nursing research,offering a lens through which to understand how individuals,families,and communities navigate adversity,maintain well-being,and thrive in the face of challenges[1].As healthcare systems worldwide grapple with increasing demands,workforce shortages,and the lingering effects of global crises such as the COVID-19 pandemic,the study of resilience has never been more relevant.This editorial explores the current status of resilience in nursing research,focusing on individual,family,and social-ecological resilience,while also considering future directions for this vital field.展开更多
基金This work was sponsored by Nanjing University Postdoctoral Foundation,the Science Foundation of Jiangsu Province Education Bureau(00KJB170001)and NSF of Jiangsu(BK99020),the State Key Basic Program:CHERES and the National Natural Science Foundation of Ch
文摘By means of the Penn State-NCAR Mesoscale Model Version 5(MM5)with a horizontal resolution of 20 km.the maintainable mechanism of Meso-β scale Convective System(Mβ CS)has been investigated on the basis of simulation of the temporal and spatial thermodynamics structure of the MβCS which occurred in Wuhan and its surroundings on 21 July 1998.The occurrence of the significant warm-core in the center of the MβCS happened in Changjiang River Basin between the Mufu Mountain and the Dabie Mountain.To the southern side of the MβCS,there exist the southwest low-level jet(LLJ)and the vertical secondary circulation in the low and middle troposphere respectively.In respect to the northern of the MβCS,the northwest jet emerges in the upper troposphere,accompanied with cold and dry atmosphere downdrafts,resulting in another secondary circulation.The foregoing mentioned vertical wind shear provides a favorable dynamical environment for the intensification and maintenance of the MβCS.Equally important,the latent heat release associated with the MβCS produces the warm center in the middle troposphere and the pressure falls.The pressure drop then accelerates air parcels toward the low leading to strong convergence as well as the intensified convection,establishing a positive feedback between the convection and the latent heat release,which is the thermodynamic mechanism of the development and maintenance of the MβCS.
基金supported by the National Key Research and Development Program of China to W.Tian (2022YFA1104400)the National Natural Science Foundation of China to T.Chen (82100959)a grant from the Sichuan Science and Technology Program to Z.Liu (2024YFFK0068)。
文摘Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation,apoptosis,and differentiation,with the Wnt/β-catenin signaling pathway playing a pivotal role.However,the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear.Smad7,a key antagonist of the TGF-βsuperfamily,is essential for maintaining tissue homeostasis and ensuring proper cellular function.Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells,resulting in small molars.Here,we identified SMAD7 expression in human dental papilla and dental pulp,colocalized with β-CATENIN and cell proliferationrelated proteins.RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs.Using lentivirus transfection,we established SMAD7-knockdown human dental papilla stem cells,which manifested remarkably blunt proliferation rate,along with diminished Wnt signaling activity.In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation.Mechanistically,we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays.Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities,indicating both direct and indirect regulatory mechanisms.These findings highlight the critical role of SMAD7 in the proliferation and diffe rentiation of human dental stem cells,which could contribute to dental tissue regeneration and engineering.
文摘Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by grants from National Nature Science Foundation of China(82272494,82472452,82402864)National Key R&D Program of China(2022YFC2502902)+4 种基金Key Project of Jiangsu Health Commission(K2023079)Natural Science Foundation of Jiangsu Province(BK20240368)Basic Research Pilot Project Suzhou(SSD2024062),China Postdoctoral Science Foundation(2024M762313)Boxi Youth Natural Science Foundation(BXQN2023014)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive.In this study,we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes.Genetically overexpressing PTEN-induced putative kinase 1(PINK1)protects against cartilage degeneration by removing defective mitochondria.PINK1 knockout aggravated cartilage damage due to impaired mitophagy.SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism.Specifically,PINK1 phosphorylated PKM2 at the Ser127 site,preserving its active tetrameric form.This inhibited nuclear translocation and the interaction withβ-catenin,resulting in a metabolic shift and increased energy production.Finally,a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguarding the structural integrity of articular joints and improving motor functions.Overall,this study provides a novel insight into the regulation of mitochondrial renewal and metabolic switches in OA.
基金supported by the National Natural Science Foundation of China (Nos. 62450056 and 62233017).
文摘1. Introduction Prognostics, known as ‘Remaining Useful Life(RUL) prediction', plays a crucial role in health management of critical systems, which is vital for maintaining the operating safety and reliability, and reducing the management costs.1Here, the RUL is usually defined as the length from the current time to the end of the useful life.
基金the National Natural Science Foundation of China(82372412)the Social Development Project of Jiangsu Province(BE2022701)+4 种基金the Top Talent Support Program for Young and Middle-aged People of the Wuxi Health Committee(BJ2020044,BJ2020057,HB2020043)the Fundamental Research Funds of the Health and Family Planning Commission of Wuxi(M202024)the Special Program for Translational Medicine Research of the Wuxi Translational Medicine Center(2020DHYB07,2020DHYB03)the Key Special Project of Precision Medicine of the Wuxi Health Commission(J202101)peking union medical college hospital talent cultivation program(UHB50192).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.
基金supported by core funding provided by Temasek Life Sciences Laboratory(to CTO)。
文摘Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158.
基金supported by the National Natural Science Foundation of China(grants 31972908,81991500,81991502,and 32030010)Beijing Natural Science Foundation(grant 7202082).
文摘Tricellulin,a key tricellular tight junction(TJ)protein,is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands.This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren’s syndrome(SS).Employing a multifaceted approach involving patient biopsies,non-obese diabetic(NOD)mice as a SS model,salivary gland acinar cell-specific tricellulin conditional knockout(TricCKO)mice,and IFN-γ-stimulated salivary gland epithelial cells,we investigated the role of tricellulin in SS-related hyposalivation.Our data revealed diminished levels of tricellulin in salivary glands of SS patients.Similarly,NOD mice displayed a reduction in tricellulin expression from the onset of the disease,concomitant with hyposecretion and an increase in salivary albumin content.Consistent with these findings,TricCKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals.Mechanistically,the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin.Treatment with AT1001,a TJ sealer,ameliorated epithelial barrier dysfunction,restored tricellulin expression,and consequently alleviated hyposalivation in NOD mice.Importantly,treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage.Collectively,we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS.Our findings highlight tricellulin as a potential therapeutic target for hyposecretion,particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
文摘As 2024 comes to an end,the pickup in consumption and robust growth in a range of sectors have bolstered confidence that the Chinese economy is right on track to meet the preset growth rate of around five percent.Benefiting from a flurry of consumption-stimulating policies and measures,China’s online retail sales surpassed RMB 14 trillion in the January-November period,a year-on-year increase of 7.4 percent.Imports and exports maintained steady growth,climbing by 4.9 percent year-on-year in renminbi terms.Value-added industrial output also expanded 5.8 percent year-on-year.The volume of express delivery parcels reached a new high of 150 billion and is expected to grow higher still given the new-year festivities ahead.
文摘In life,we are bound to encounter various difficulties and setbacks.However,it is of great significance to maintain a positive attitude when were facing these challenges.For me,this lesson was deeply impressed upon me during a particularly tough period.
文摘If you are to choose an event that can best represent China’s culture,undoubtedly,it will be the Spring Festival,or the Chinese Lunar New Year.It is a cherished occasion for families to get together,extend best wishes to the people around them,and maintain friendships.
文摘China’s economy is expected to remain stable throughout 2025.According to projections by the Center for Forecasting Science of the Academy of Mathematics and Systems Science under the Chinese Academy of Sciences,China’s GDP(gross domestic product)growth should settle at around 4.8 percent this year and will likely hit 5 percent if the government’s stimulus package is effectively implemented.I personally believe that the Chinese economy will maintain growth of about 4.6 percent in 2025 with robust performance in the first and fourth quarters and slower economic activity in the second and third quarters.
文摘The annual Central Economic Work Conference 2024,held on December 11-12,set the overall goal and policy framework for Chinese economy in 2025,a crucial year in China’s economic development as the final year of the 14th Five-Year Plan(FYP)and the preparation for the 15th FYP.A series of incremental fiscal and monetary policies adopted since the end of September has seen their initial effects in stabilizing stock markets and boosting consumption and production and thus enhanced the confidence of meeting the GDP goal for 2024.In the face of complicated external challenges and domestic difficulties-inadequate effective demand,overcapacity in some sectors and weak expectations,it is crucial to maintain stable growth in 2025.The Central Economic Work Conference 2024 set the general goal of 2025 on maintaining stable growth,employment and consumer prices.
文摘China-Africa relations maintained their upward trajectory in 2024,with new plans for future cooperation taking shape.Chinese President Xi Jinping described the China-Africa partnership as being at its best in history.The Beijing Summit of the Forum on China-Africa Cooperation(FOCAC),held in September 2024,elevated bilateral ties between China and African countries with diplomatic relations with China to a strategic level.It also redefined China-Africa relations as an“all-weather China-Africa community with a shared future for the new era.”This signifies that China and Africa will remain steadfast friends and close development partners,regardless of changes in the international landscape.
文摘The year 2025 marks the 45th anniversary of the establishment of diplomatic relations between China and Zimbabwe.During this period,China-Zimbabwe economic cooperation has deepened,especially in the fields of infrastructure construction,mineral resource development,and agriculture.The two sides have maintained a high degree of political mutual trust and have cooperated closely in international affairs.Cultural exchanges and people-to-people contacts have expanded,and both nations continue to work together to further deepen their partnership.
文摘Resilience has emerged as a critical concept in nursing research,offering a lens through which to understand how individuals,families,and communities navigate adversity,maintain well-being,and thrive in the face of challenges[1].As healthcare systems worldwide grapple with increasing demands,workforce shortages,and the lingering effects of global crises such as the COVID-19 pandemic,the study of resilience has never been more relevant.This editorial explores the current status of resilience in nursing research,focusing on individual,family,and social-ecological resilience,while also considering future directions for this vital field.
