The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin a...The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.展开更多
BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains u...BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.展开更多
Cooperative guidance is a method for achieving combat objectives through information sharing and cooperative effects,and has emerged as a significant research area in the fields of missile guidance and systematic warf...Cooperative guidance is a method for achieving combat objectives through information sharing and cooperative effects,and has emerged as a significant research area in the fields of missile guidance and systematic warfare.This study presents a systematic review and analysis of current research on cooperative guidance.First,a bibliometric analysis is conducted on 513 articles using the Scopus database and CiteSpace software to assess keyword clustering,keyword cooccurrence,and keyword burst,and to later visualize the results.Second,fundamental theories of cooperative guidance,including relative motion modeling methods,algebraic graph theory,and multi-agent consensus theory,are summarized.Subsequently,an overview of current cooperative laws and corresponding analysis methods is provided,with categorization based on the cooperative structure and convergence performance.Finally,we summarize current research developments based on five perspectives and propose a developmental framework based on five layers(cyber,physical,decision,information,and system),discussing potential future advancements in cooperative terminal guidance.This framework emphasizes five key areas of research:networked,heterogeneous,integrated,intelligent,and group cooperations,with the goal of offering trends and insights for futurework.展开更多
Unmanned aerial vehicles(UAVs)have become crucial tools in moving target tracking due to their agility and ability to operate in complex,dynamic environments.UAVs must meet several requirements to achieve stable track...Unmanned aerial vehicles(UAVs)have become crucial tools in moving target tracking due to their agility and ability to operate in complex,dynamic environments.UAVs must meet several requirements to achieve stable tracking,including maintaining continuous target visibility amidst occlusions,ensuring flight safety,and achieving smooth trajectory planning.This paper reviews the latest advancements in UAV-based target tracking,highlighting information prediction,tracking strategies,and swarm cooperation.To address challenges including target visibility and occlusion,real-time prediction and tracking in dynamic environments,flight safety and coordination,resource management and energy efficiency,the paper identifies future research directions aimed at improving the performance,reliability,and scalability of UAV tracking system.展开更多
The issues of fossil energy shortage and environmental pollution caused by the excessive consumption of conventional fossil fuels necessitates the exploration of renewable and clean energy sources such as hydrogen,whi...The issues of fossil energy shortage and environmental pollution caused by the excessive consumption of conventional fossil fuels necessitates the exploration of renewable and clean energy sources such as hydrogen,which is viable alternative to traditional energy sources in view of its high energy density and nonpolluting nature.In this regard,photocatalytic technology powered by inexhaustible solar energy is an ideal hydrogen production method.The recently developed copper-and zinc-based multinary metal sulfide(MMS)semiconductor photocatalysts exhibit the advantages of suitable bandgap,wide light-harvesting range,and flexible elemental composition,thus possessing great potential for achieving considerable photocatalytic hydrogen evolution(PHE)performance.Despite great progress has been achieved,the current photocatalysts still cannot meet the commercial application demands,which highlights the mechanisms understanding and optimization strategies for efficient PHE.Herein,the basic mechanisms of PHE,and effective optimization strategies are firstly introduced.Afterwards,the research process and the performance of copper-and zinc-based MMS photocatalysts,are thoroughly reviewed.Finally,the unresolved issues,and challenges hindering the achievement of overall water splitting have been discussed.展开更多
In this work,for the first time,it is demonstrated that during the insertion/extraction of Na ions,the structural evolution at the Na_(4)site at a voltage range of 3-4 V is a key factor for the capacity decay of Na_(4...In this work,for the first time,it is demonstrated that during the insertion/extraction of Na ions,the structural evolution at the Na_(4)site at a voltage range of 3-4 V is a key factor for the capacity decay of Na_(4)Fe_(3)(PO_(4))_(2)P_(2)O_(7)(NFPP).Herein,a strategy of introducing columnar potassium ions at the Na_(4)site is proposed to address the aforementioned challenge.As a cathode material for sodium-ion batteries,the K_(0.12)Na_(3.88)Fe_(3)(PO_(4))_(2)P_(2)O_(7)/C(K-NFPP)composite enhances the reversibility of Na_(4)extraction.Specifically,the K-NFPP exhibits an initial discharge capacity of 107.8 mAh g^(-1)at a high current density of 5 C,with a capacity retention of 91.4% after 2000 cycles,outperforming the pristine NFPP material(81.1 m Ah g^(-1)and 67.1%).At 5 C,the K-NFPP also retains 81.5% of the reversible capacity at 0.1 C,whereas the NFPP only retains 68.3%.Moreover,the K-NFPP-based full-cell delivers an initial capacity of 110.1 m Ah g^(-1)at 1 C,with a capacity retention of 90% after 100 cycles.It is found that in comparison to K-doping of the Na1,Na2,and Na3 sites,K-doping at the Na4 site effectively optimizes the band gap and stabilizes the crystal structure,thereby reducing lattice changes of FeO_(6)evolution during Na^(+)insertion/extraction.As a result,the introduction of columnar potassium ions significantly enhances the capacity contribution of the Na_(4)site,optimizes reaction kinetics,and effectively mitigates the capacity decay of NFPP cathodes.It is believed that this study offers a new entry point for the application of NFPP in high-voltage sodium storage.展开更多
This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The inp...This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of ...BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.展开更多
Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autoph...Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.展开更多
BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these patients.CASE SUMMARY This report describes an 83-year-old female pat...BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these patients.CASE SUMMARY This report describes an 83-year-old female patient with a 30-year history of type 2 diabetes(T2DM)who had struggled to control her blood sugar for more than a year.She had a history of high blood pressure for 30 years,had undergone continuous ambulatory peritoneal dialysis for more than two years,was 163 cm tall,weighed 77 kg,and had a body mass index of 28.98 kg/m2.Despite intensive insulin therapy at a daily dose of 150 units,adding Dorzagliatin at a dosage of 75 mg orally twice daily led to immediate blood sugar improvement and a gradual reduction in insulin dosage.After one month of follow-up,the fasting plasma glucose was 6-8 mmol/L,and the 2-hour postprandial glucose was 8-12 mmol/L.CONCLUSION To our knowledge,this report is the first to use Dorzagliatin to treat type 2 diabetes peritoneal dialysis patients with challenging glucose control.Dorzagliatin,a novel glucokinase activator primarily metabolized by the liver,exhibits no pharmacokinetic differences among patients with varying degrees of chronic kidney disease.It has a high plasma protein binding rate and may not be cleared by peritoneal dialysis,potentially offering a new glycemic control option for Type 2 diabetic patients on peritoneal dialysis.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32070534(to WY),32370567(to WY),82371874(to XL),81830032(to XL),82071421(to SL)Key Field Research and Development Program of Guangdong Province,No.2018B030337001(to XL)+2 种基金Guangzhou Key Research Program on Brain Science,No.202007030008(to XL)Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(to XL)Guangdong Basic and Applied Basic Research Foundation,Nos.2022A1515012301(to WY),2023B1515020031(to WY).
文摘The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.
基金Supported by National Natural Science Foundation of China,No.82360136Jiangxi Clinical Research Center for Gastroenterology,No.20223BCG74011.
文摘BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.
基金supported by the National Natural Science Foundation of China(No.62173274)the National Key R&D Program of China(No.2019YFA0405300)+4 种基金the Natural Science Foundation of Hunan Province of China(Nos.2021JJ10045 and 2025JJ60072)the Open Research Subject of State Key Laboratory of Intelligent Game(No.ZBKF-24-01)the Postdoctoral Fellowship Program of CPSF(No.GZB20240989)the China Postdoctoral Science Foundation(No.2024M754304)the Aeronautical Science Foundation of China(No.2023Z005030001).
文摘Cooperative guidance is a method for achieving combat objectives through information sharing and cooperative effects,and has emerged as a significant research area in the fields of missile guidance and systematic warfare.This study presents a systematic review and analysis of current research on cooperative guidance.First,a bibliometric analysis is conducted on 513 articles using the Scopus database and CiteSpace software to assess keyword clustering,keyword cooccurrence,and keyword burst,and to later visualize the results.Second,fundamental theories of cooperative guidance,including relative motion modeling methods,algebraic graph theory,and multi-agent consensus theory,are summarized.Subsequently,an overview of current cooperative laws and corresponding analysis methods is provided,with categorization based on the cooperative structure and convergence performance.Finally,we summarize current research developments based on five perspectives and propose a developmental framework based on five layers(cyber,physical,decision,information,and system),discussing potential future advancements in cooperative terminal guidance.This framework emphasizes five key areas of research:networked,heterogeneous,integrated,intelligent,and group cooperations,with the goal of offering trends and insights for futurework.
基金financial support provided by the Natural Science Foundation of Hunan Province of China(Grant No.2021JJ10045)the Open Research Subject of State Key Laboratory of Intelligent Game(Grant No.ZBKF-24-01)+1 种基金the Postdoctoral Fellowship Program of CPSF(Grant No.GZB20240989)the China Postdoctoral Science Foundation(Grant No.2024M754304)。
文摘Unmanned aerial vehicles(UAVs)have become crucial tools in moving target tracking due to their agility and ability to operate in complex,dynamic environments.UAVs must meet several requirements to achieve stable tracking,including maintaining continuous target visibility amidst occlusions,ensuring flight safety,and achieving smooth trajectory planning.This paper reviews the latest advancements in UAV-based target tracking,highlighting information prediction,tracking strategies,and swarm cooperation.To address challenges including target visibility and occlusion,real-time prediction and tracking in dynamic environments,flight safety and coordination,resource management and energy efficiency,the paper identifies future research directions aimed at improving the performance,reliability,and scalability of UAV tracking system.
文摘The issues of fossil energy shortage and environmental pollution caused by the excessive consumption of conventional fossil fuels necessitates the exploration of renewable and clean energy sources such as hydrogen,which is viable alternative to traditional energy sources in view of its high energy density and nonpolluting nature.In this regard,photocatalytic technology powered by inexhaustible solar energy is an ideal hydrogen production method.The recently developed copper-and zinc-based multinary metal sulfide(MMS)semiconductor photocatalysts exhibit the advantages of suitable bandgap,wide light-harvesting range,and flexible elemental composition,thus possessing great potential for achieving considerable photocatalytic hydrogen evolution(PHE)performance.Despite great progress has been achieved,the current photocatalysts still cannot meet the commercial application demands,which highlights the mechanisms understanding and optimization strategies for efficient PHE.Herein,the basic mechanisms of PHE,and effective optimization strategies are firstly introduced.Afterwards,the research process and the performance of copper-and zinc-based MMS photocatalysts,are thoroughly reviewed.Finally,the unresolved issues,and challenges hindering the achievement of overall water splitting have been discussed.
基金financial support from the National Natural Science Foundation of China(52272237,22279101 and 22172117)the Natural Science Foundation of Shaanxi(2020JC-41 and 2024JC-YBQN-0141)+2 种基金the Scientific Research Program Funded by the Education Department of Shaanxi Provincial Government(22JP056)the S&T Program of Energy Shaanxi Laboratory(ESLB202402)the Foshan Science and Technology Innovation Team Project(1920001004098)。
文摘In this work,for the first time,it is demonstrated that during the insertion/extraction of Na ions,the structural evolution at the Na_(4)site at a voltage range of 3-4 V is a key factor for the capacity decay of Na_(4)Fe_(3)(PO_(4))_(2)P_(2)O_(7)(NFPP).Herein,a strategy of introducing columnar potassium ions at the Na_(4)site is proposed to address the aforementioned challenge.As a cathode material for sodium-ion batteries,the K_(0.12)Na_(3.88)Fe_(3)(PO_(4))_(2)P_(2)O_(7)/C(K-NFPP)composite enhances the reversibility of Na_(4)extraction.Specifically,the K-NFPP exhibits an initial discharge capacity of 107.8 mAh g^(-1)at a high current density of 5 C,with a capacity retention of 91.4% after 2000 cycles,outperforming the pristine NFPP material(81.1 m Ah g^(-1)and 67.1%).At 5 C,the K-NFPP also retains 81.5% of the reversible capacity at 0.1 C,whereas the NFPP only retains 68.3%.Moreover,the K-NFPP-based full-cell delivers an initial capacity of 110.1 m Ah g^(-1)at 1 C,with a capacity retention of 90% after 100 cycles.It is found that in comparison to K-doping of the Na1,Na2,and Na3 sites,K-doping at the Na4 site effectively optimizes the band gap and stabilizes the crystal structure,thereby reducing lattice changes of FeO_(6)evolution during Na^(+)insertion/extraction.As a result,the introduction of columnar potassium ions significantly enhances the capacity contribution of the Na_(4)site,optimizes reaction kinetics,and effectively mitigates the capacity decay of NFPP cathodes.It is believed that this study offers a new entry point for the application of NFPP in high-voltage sodium storage.
基金supported by the National Natural Science Foundation of China(U2241221).
文摘This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
基金supported by the National Natural Science Foundation of China(82102315).
文摘BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.
基金the National Natural Science Foundation of China(Nos.22307009,82374155,82073997,82104376)the Sichuan Science and Technology Program(Nos.2023NSFSC1108,2024NSFTD0023)+1 种基金the Postdoctoral Research Project of Sichuan Provincethe Xinglin Scholar Research Promotion Project of Chengdu University of TCM.
文摘Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.
文摘BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these patients.CASE SUMMARY This report describes an 83-year-old female patient with a 30-year history of type 2 diabetes(T2DM)who had struggled to control her blood sugar for more than a year.She had a history of high blood pressure for 30 years,had undergone continuous ambulatory peritoneal dialysis for more than two years,was 163 cm tall,weighed 77 kg,and had a body mass index of 28.98 kg/m2.Despite intensive insulin therapy at a daily dose of 150 units,adding Dorzagliatin at a dosage of 75 mg orally twice daily led to immediate blood sugar improvement and a gradual reduction in insulin dosage.After one month of follow-up,the fasting plasma glucose was 6-8 mmol/L,and the 2-hour postprandial glucose was 8-12 mmol/L.CONCLUSION To our knowledge,this report is the first to use Dorzagliatin to treat type 2 diabetes peritoneal dialysis patients with challenging glucose control.Dorzagliatin,a novel glucokinase activator primarily metabolized by the liver,exhibits no pharmacokinetic differences among patients with varying degrees of chronic kidney disease.It has a high plasma protein binding rate and may not be cleared by peritoneal dialysis,potentially offering a new glycemic control option for Type 2 diabetic patients on peritoneal dialysis.
