Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maiz...Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maize(Zea mays L.),we analyzed Iso-Seq data from anthers collected at 10 developmental stages,together with strand-specific RNA-seq,CAGE-seq,and PAS-seq data.Of the 152,026 high-confidence full-length isoforms identified,68.8%have not been described;these include 22,365 isoforms that originate from previously unannotated loci and 82,167 novel isoforms that originate from annotated protein-coding genes.Using our newly developed strategy to detect dynamic expression patterns of isoforms,we identify 13,899 differentially variable regions(DVRs);surprisingly,1275 genes contain more than two DVRs,revealing highly efficient utilization of limited genic regions.We identify 7876 long non-coding RNAs(lncRNAs)from 4098 loci,most of which were preferentially expressed during cell differentiation and meiosis.We also detected 371 long-range interactions involving intergenic lncRNAs(lincRNAs);interestingly,243 were lincRNA-gene ones,and the interacting genes were highly expressed in anthers,suggesting that many potential lncRNA regulators of key genes are required for anther development.This study provides valuable resources and fundamental information for studying the essential transcripts of key genes during anther development.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
The susceptibility of ore particles to electrical breakdown plays a critical role for high voltage pulse(HVP)breakage,yet its quantitative characterization still lacks deep understanding.Two indicators,namely breakdow...The susceptibility of ore particles to electrical breakdown plays a critical role for high voltage pulse(HVP)breakage,yet its quantitative characterization still lacks deep understanding.Two indicators,namely breakdown delay time(T_(d))and breakdown strength(E_(b))were compared,based on analysis on the two breakdown modes namely wavefront mode and post-wave mode.It was found that T_(d) is more suitable to characterize the susceptibility of ore particles to electrical breakdown in HVP breakage than E_(b).A probabilistic model based on the Weibull distribution is developed to describe the relation of breakdown probability to T_(d).Regression analyses were conducted to investigate how operating parameters and particle properties influence Td and size reduction degree of ore particles in HVP breakage.The regressed models demonstrate potential capability to predict metallic minerals content and HVP breakage degree based on operating parameters and particle properties.展开更多
Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to human...Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.展开更多
This study traces the development of the Shanghai Typhoon Model(SHTM)from a traditional physics-based regional model toward a data-driven,machine-learning typhoon forecasting system.After upgrading its initial and bou...This study traces the development of the Shanghai Typhoon Model(SHTM)from a traditional physics-based regional model toward a data-driven,machine-learning typhoon forecasting system.After upgrading its initial and boundary conditions,SHTM now leverages large-scale constraints from machine-learning weather prediction(MLWP)models,resulting in an ML–physics hybrid framework.During Typhoon Danas(2025),the hybrid SHTM achieves substantially lower track errors than both the advanced ECMWF Integrated Forecasting System(IFS)and leading MLWP models such as PanGu and FuXi.Furthermore,the hybrid SHTM consistently maintains mean track errors below 200 km up to a forecast lead time of 108 hours,representing a significant advancement in forecast accuracy.In addition,this study highlights the technical roadmap for transitioning from a physics-based typhoon model to a fully data-driven ML typhoon forecast system.It also emphasizes that advances in the physical modeling framework provide a critical foundation for further improving the performance of future data-driven ML typhoon models.展开更多
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 multi-target assignment(MTA)problem,a crucial challenge in command control,mission planning,and a fundamental research focus in military operations,has garnered significant attention over the years.Extensively stu...The multi-target assignment(MTA)problem,a crucial challenge in command control,mission planning,and a fundamental research focus in military operations,has garnered significant attention over the years.Extensively studied across various domains such as land,sea,air,space,and electronics,the MTA problem has led to the emergence of numerous models and algorithms.To delve deeper into this field,this paper starts by conducting a bibliometric analysis on 463 Scopus database papers using CiteSpace software.The analysis includes examining keyword clustering,co-occurrence,and burst,with visual representations of the results.Following this,the paper provides an overview of current classification and modeling techniques for addressing the MTA problem,distinguishing between static multi-target assignment(SMTA)and dynamic multi-target assignment(DMTA).Subsequently,existing solution algorithms for the MTA problem are reviewed,generally falling into three categories:exact algorithms,heuristic algorithms,and machine learning algorithms.Finally,a development framework is proposed based on the"HIGH"model(high-speed,integrated,great,harmonious)to guide future research and intelligent weapon system development concerning the MTA problem.This framework emphasizes application scenarios,modeling mechanisms,solution algorithms,and system efficiency to offer a roadmap for future exploration in this area.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
Aerodynamic evaluation under multi-condition is indispensable for the design of aircraft,and the requirement for mass data still means a high cost.To address this problem,we propose a novel point-cloud multi-condition...Aerodynamic evaluation under multi-condition is indispensable for the design of aircraft,and the requirement for mass data still means a high cost.To address this problem,we propose a novel point-cloud multi-condition aerodynamics transfer learning(PCMCA-TL)framework that enables aerodynamic prediction in data-scarce sce-narios by transferring knowledge from well-learned scenarios.We modified the PointNeXt segmentation archi-tecture to a PointNeXtReg+regression model,including a working condition input module.The model is first pre-trained on a public dataset with 2000 shapes but only one working condition and then fine-tuned on a multi-condition small-scale spaceplane dataset.The effectiveness of the PCMCA-TL framework is verified by comparing the pressure coefficients predicted by direct training,pre-training,and TL models.Furthermore,by comparing the aerodynamic force coefficients calculated by predicted pressure coefficients in seconds with the correspond-ing CFD results obtained in hours,the accuracy highlights the development potential of deep transfer learning in aerodynamic evaluation.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
The stability of supersonic inlets faces challenges due to various changes in flight conditions,and flow control methods that address shock wave/boundary layer interactions under only one set of conditions cannot meet...The stability of supersonic inlets faces challenges due to various changes in flight conditions,and flow control methods that address shock wave/boundary layer interactions under only one set of conditions cannot meet developmental requirements.This paper proposes an adaptive bump control scheme and employs dynamic mesh technology for numerical simulation to investigate the unsteady control effects of adaptive bumps.The obtained results indicate that the use of moving bumps to control shock wave/boundary layer interactions is feasible.The adaptive control effects of five different bump speeds are evaluated.Within the range of bump speeds studied,the analysis of the flow field structure reveals the patterns of change in the separation zone area during the control process,as well as the relationship between the bump motion speed and the control effect on the separation zone.It is concluded that the moving bump endows the boundary layer with additional energy.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
基金supported by the Excellent Young Scientists Fund(Category B)(32422063)the National Key Research and Development Program of China(2022YFF1003500)the Zhengzhou University Qiushi Postdoctoral Research Funding Program.For open access,the authors have applied for a Creative Commons Attribution(CC BY)license for any Author Accepted Manuscript version arising from this submission.
文摘Anther is a key male reproductive organ that is essential for the plant life cycle,from the sporophyte to the gametophyte generation.To explore the isoform-level transcriptional landscape of developing anthers in maize(Zea mays L.),we analyzed Iso-Seq data from anthers collected at 10 developmental stages,together with strand-specific RNA-seq,CAGE-seq,and PAS-seq data.Of the 152,026 high-confidence full-length isoforms identified,68.8%have not been described;these include 22,365 isoforms that originate from previously unannotated loci and 82,167 novel isoforms that originate from annotated protein-coding genes.Using our newly developed strategy to detect dynamic expression patterns of isoforms,we identify 13,899 differentially variable regions(DVRs);surprisingly,1275 genes contain more than two DVRs,revealing highly efficient utilization of limited genic regions.We identify 7876 long non-coding RNAs(lncRNAs)from 4098 loci,most of which were preferentially expressed during cell differentiation and meiosis.We also detected 371 long-range interactions involving intergenic lncRNAs(lincRNAs);interestingly,243 were lincRNA-gene ones,and the interacting genes were highly expressed in anthers,suggesting that many potential lncRNA regulators of key genes are required for anther development.This study provides valuable resources and fundamental information for studying the essential transcripts of key genes during anther development.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
基金The financial supports from National Natural Science Foundation of China(Nos.52574313,52204272 and 52074091)to this project。
文摘The susceptibility of ore particles to electrical breakdown plays a critical role for high voltage pulse(HVP)breakage,yet its quantitative characterization still lacks deep understanding.Two indicators,namely breakdown delay time(T_(d))and breakdown strength(E_(b))were compared,based on analysis on the two breakdown modes namely wavefront mode and post-wave mode.It was found that T_(d) is more suitable to characterize the susceptibility of ore particles to electrical breakdown in HVP breakage than E_(b).A probabilistic model based on the Weibull distribution is developed to describe the relation of breakdown probability to T_(d).Regression analyses were conducted to investigate how operating parameters and particle properties influence Td and size reduction degree of ore particles in HVP breakage.The regressed models demonstrate potential capability to predict metallic minerals content and HVP breakage degree based on operating parameters and particle properties.
基金State Key Laboratory Special Fund,Grant/Award Number:2060204Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling,Grant/Award Number:Peking University,202411+3 种基金The Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2022-I2M-1-020 and 2023-I2M-2-001the National Key Research and Development Program of China from the Ministry of Science and Technology,Grant/Award Number:2021YFF0702802。
文摘Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.
基金supported by the Special Project-Original Exploration(Grant No.42450163)the National Youth Science Foundation of China Project(Grant No.4240050560)the Research and Development of Key Technologies for Artificial Intelligence Regional Typhoon Forecasting Model project.
文摘This study traces the development of the Shanghai Typhoon Model(SHTM)from a traditional physics-based regional model toward a data-driven,machine-learning typhoon forecasting system.After upgrading its initial and boundary conditions,SHTM now leverages large-scale constraints from machine-learning weather prediction(MLWP)models,resulting in an ML–physics hybrid framework.During Typhoon Danas(2025),the hybrid SHTM achieves substantially lower track errors than both the advanced ECMWF Integrated Forecasting System(IFS)and leading MLWP models such as PanGu and FuXi.Furthermore,the hybrid SHTM consistently maintains mean track errors below 200 km up to a forecast lead time of 108 hours,representing a significant advancement in forecast accuracy.In addition,this study highlights the technical roadmap for transitioning from a physics-based typhoon model to a fully data-driven ML typhoon forecast system.It also emphasizes that advances in the physical modeling framework provide a critical foundation for further improving the performance of future data-driven ML typhoon models.
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.
基金the financial support provided by the National Natural Science Foundation of China(NSFC)(Grant No.62173274)the National Key R&D Program of China(Grant No.2019YFA0405300)+4 种基金the Natural Science Foundation of Hunan Province of China(Grant No.2021JJ10045)the Practice and Innovation Funds for Graduate Students of Northwestern Polytechnical University(Grant No.PF2023046)the Open Research Subject of State Key Laboratory of Intelligent Game(Grant No.ZBKF-24-01)the Postdoctoral Fellowship Program of CPSF(No.GZB20240989)the China Postdoctoral Science Foundation(Grant No.2024M754304)。
文摘The multi-target assignment(MTA)problem,a crucial challenge in command control,mission planning,and a fundamental research focus in military operations,has garnered significant attention over the years.Extensively studied across various domains such as land,sea,air,space,and electronics,the MTA problem has led to the emergence of numerous models and algorithms.To delve deeper into this field,this paper starts by conducting a bibliometric analysis on 463 Scopus database papers using CiteSpace software.The analysis includes examining keyword clustering,co-occurrence,and burst,with visual representations of the results.Following this,the paper provides an overview of current classification and modeling techniques for addressing the MTA problem,distinguishing between static multi-target assignment(SMTA)and dynamic multi-target assignment(DMTA).Subsequently,existing solution algorithms for the MTA problem are reviewed,generally falling into three categories:exact algorithms,heuristic algorithms,and machine learning algorithms.Finally,a development framework is proposed based on the"HIGH"model(high-speed,integrated,great,harmonious)to guide future research and intelligent weapon system development concerning the MTA problem.This framework emphasizes application scenarios,modeling mechanisms,solution algorithms,and system efficiency to offer a roadmap for future exploration in this area.
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 Natural Science Foundation of Hunan Province of China(Grant No.2021JJ10045).
文摘Aerodynamic evaluation under multi-condition is indispensable for the design of aircraft,and the requirement for mass data still means a high cost.To address this problem,we propose a novel point-cloud multi-condition aerodynamics transfer learning(PCMCA-TL)framework that enables aerodynamic prediction in data-scarce sce-narios by transferring knowledge from well-learned scenarios.We modified the PointNeXt segmentation archi-tecture to a PointNeXtReg+regression model,including a working condition input module.The model is first pre-trained on a public dataset with 2000 shapes but only one working condition and then fine-tuned on a multi-condition small-scale spaceplane dataset.The effectiveness of the PCMCA-TL framework is verified by comparing the pressure coefficients predicted by direct training,pre-training,and TL models.Furthermore,by comparing the aerodynamic force coefficients calculated by predicted pressure coefficients in seconds with the correspond-ing CFD results obtained in hours,the accuracy highlights the development potential of deep transfer learning in aerodynamic evaluation.
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 Key R&D Program of China(Grant No.2019YFA0405300)the National Natural Science Foundation of China(Grant No.11972368)the Natural Science Foundation of Hunan Province(Grant No.2021JJ10045).
文摘The stability of supersonic inlets faces challenges due to various changes in flight conditions,and flow control methods that address shock wave/boundary layer interactions under only one set of conditions cannot meet developmental requirements.This paper proposes an adaptive bump control scheme and employs dynamic mesh technology for numerical simulation to investigate the unsteady control effects of adaptive bumps.The obtained results indicate that the use of moving bumps to control shock wave/boundary layer interactions is feasible.The adaptive control effects of five different bump speeds are evaluated.Within the range of bump speeds studied,the analysis of the flow field structure reveals the patterns of change in the separation zone area during the control process,as well as the relationship between the bump motion speed and the control effect on the separation zone.It is concluded that the moving bump endows the boundary layer with additional energy.
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.
