Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the dis...Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.展开更多
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
HIV-related stigma,discrimination,and other forms of oppression can severely undermine adherence to antiretroviral therapy(ART)among people living with HIV[1].For example,Kerr et al.reveal that perceived discriminatio...HIV-related stigma,discrimination,and other forms of oppression can severely undermine adherence to antiretroviral therapy(ART)among people living with HIV[1].For example,Kerr et al.reveal that perceived discrimination based on sexual orientation in healthcare settings significantly reduces ART adherence[1].This highlights the urgent need for targeted strategies to address stigma,discrimination,and social marginalization,especially within healthcare facilities,to improve HIV care outcomes.展开更多
Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However...Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However,despite some advancements in recent years,no targeted antifibrotic strategies for OSF have been approved;likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined.In this review,we briefly introduce the epidemiology and etiology of OSF.Then,we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors,secretion function,and activation of ECM-producing myofibroblasts.In addition,we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF.Finally,we summarize strategies to interrupt key mechanisms that cause OSF,including modulation of the ECM,inhibition of inflammation,improvement of vascular disturbance.This review will provide potential routes for developing novel anti-OSF therapeutics.展开更多
In response to the problems of low sampling efficiency,strong randomness of sampling points,and the tortuous shape of the planned path in the traditional rapidly-exploring random tree(RRT)algorithm and bidirectional R...In response to the problems of low sampling efficiency,strong randomness of sampling points,and the tortuous shape of the planned path in the traditional rapidly-exploring random tree(RRT)algorithm and bidirectional RRT algorithm used for unmanned aerial vehicle(UAV)path planning in complex environments,an improved bidirectional RRT algorithm was proposed.The algorithm firstly adopted a goal-oriented strategy to guide the sampling points towards the target point,and then the artificial potential field acted on the random tree nodes to avoid collision with obstacles and reduced the length of the search path,and the random tree node growth also combined the UAV’s own flight constraints,and by combining the triangulation method to remove the redundant node strategy and the third-order B-spline curve for the smoothing of the trajectory,the planned path was better.The planned paths were more optimized.Finally,the simulation experiments in complex and dynamic environments showed that the algorithm effectively improved the speed of trajectory planning and shortened the length of the trajectory,and could generate a safe,smooth and fast trajectory in complex environments,which could be applied to online trajectory planning.展开更多
Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laborato...Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.展开更多
Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalli...Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.展开更多
Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer.Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells.Inhibiting tumor cell cholesterol uptake ...Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer.Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells.Inhibiting tumor cell cholesterol uptake or biosynthesis pathways,through the modulation of receptors and enzymes such as liver X receptor and sterolregulatory element binding protein 2,effectively restrains lung tumor growth.Similarly,promoting cholesterol excretion yields comparable effects.Cholesterol metabolites,including oxysterols and isoprenoids,play a crucial role in regulating cholesterol metabolism within tumor cells,consequently impacting cancer progression.In lung cancer patients,both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth,proliferation,and metastasis.The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells,B cells,macrophages,myeloid-derived suppressor cells,among others.Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments.Statins,targeting the cholesterol biosynthesis pathway,are widely employed in lung cancer treatment,either as standalone agents or in combination with other drugs.Additionally,drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer.In this review,we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.展开更多
Multi-object tracking(MOT)has seen rapid improvements in recent years.However,frequent occlusion remains a significant challenge in MOT,as it can cause targets to become smaller or disappear entirely,resulting in lowq...Multi-object tracking(MOT)has seen rapid improvements in recent years.However,frequent occlusion remains a significant challenge in MOT,as it can cause targets to become smaller or disappear entirely,resulting in lowquality targets,leading to trajectory interruptions and reduced tracking performance.Different from some existing methods,which discarded the low-quality targets or ignored low-quality target attributes.LQTTrack,with a lowquality association strategy(LQA),is proposed to pay more attention to low-quality targets.In the association scheme of LQTTrack,firstly,multi-scale feature fusion of FPN(MSFF-FPN)is utilized to enrich the feature information and assist in subsequent data association.Secondly,the normalized Wasserstein distance(NWD)is integrated to replace the original Inter over Union(IoU),thus overcoming the limitations of the traditional IoUbased methods that are sensitive to low-quality targets with small sizes and enhancing the robustness of low-quality target tracking.Moreover,the third association stage is proposed to improve the matching between the current frame’s low-quality targets and previously interrupted trajectories from earlier frames to reduce the problem of track fragmentation or error tracking,thereby increasing the association success rate and improving overall multi-object tracking performance.Extensive experimental results demonstrate the competitive performance of LQTTrack on benchmark datasets(MOT17,MOT20,and DanceTrack).展开更多
Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enor...Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.展开更多
The reasonable marketing orientation is related to the survival and the development of the enterprises. According to the disadvantages and superiority of the middle and small sized enterprises of our country, this pap...The reasonable marketing orientation is related to the survival and the development of the enterprises. According to the disadvantages and superiority of the middle and small sized enterprises of our country, this paper analyzes the new thought about the marketing orientation from the aspects of marketing product orientation, marketing way orientation, marketing target orientation, marketing strategy orientation and marketing idea orientation. It has great theoretical and practical significance.展开更多
Sperm motility and morphology are indispensable for sperm-egg interaction and successful fertilization.However,the RNA splicing mechanisms in an m6A-dependent manner regulating spermiogenesis-related genes remain poor...Sperm motility and morphology are indispensable for sperm-egg interaction and successful fertilization.However,the RNA splicing mechanisms in an m6A-dependent manner regulating spermiogenesis-related genes remain poorly defined,and targeted therapy strategies to restore impaired sperm motility and morphology are lacking.In this study,we identify heterogeneous nuclear ribonucleoprotein R(hnRNPR)as a critical m6A-dependent splicing mediator.Pathogenic mutations in HNRNPR cause sperm motility decline,morphological abnormality,and male infertility in both humans and mice.Mechanistically,Hnrnpr mutation disrupts m6A-dependent splicing of Skap2 pre-mRNA,thus impairing cytoskeletal structure and mitochondrial organization in sperm.Consistently,specific knockout of Skap2 in male germ cells displays sperm abnormalities,which phenocopy those observed in humans and mice with Hnrnpr mutants,unveiling a functional hnRNPR-SKAP2 axis.Leveraging these insights,we developed a therapeutic strategy to restore sperm motility and morphology,relying on extracellular vesicle-mediated SKAP2 delivery to enter the efferent ductules of the testicles,which could promote sperm cytoskeletal remodeling and mitochondrial organization.Notably,the co-culture of extracellular vesicle SKAP2 with human and mouse sperms also significantly enhanced the sperm motility.Altogether,these findings identify hnRNPR as a pivotal regulator of m6A-mediated Skap2 splicing during spermiogenesis and highlight extracellular vesicle SKAP2 as a promising therapeutic target for poor sperm quality and male infertility.展开更多
Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coro...Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coronavirus disease 2019(COVID-19)have been encountered with a high risk of ARDS,underscoring the urgency for exploiting effective therapy.However,proper medications for ARDS are still lacking due to poor pharmacokinetics,non-specific side effects,inability to surmount pulmonary barrier,and inadequate management of heterogeneity.The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery.Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy,which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment.Through passive,active,or physicochemical targeting,nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment,thereby showing good therapeutic activity and reduced toxicity.This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy,highlights the strategies for targeted treatment of lung inflammation,presents the innovative drug delivery systems,and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.展开更多
mRNA therapeutics have significantly evolved within the life sciences,particularly in applications such as vaccines,tumor immunotherapy,protein replacement,gene editing,and monoclonal antibody therapy.To fully realize...mRNA therapeutics have significantly evolved within the life sciences,particularly in applications such as vaccines,tumor immunotherapy,protein replacement,gene editing,and monoclonal antibody therapy.To fully realize the potential of mRNA drugs and mitigate the adverse effects,substantial vector materials have been developed for delivery of these pharmaceutical agents.Lipid nanoparticles(LNPs)represent the most clinically advanced mRNA carriers,recognized by U.S.Food and Drug Administration approved mRNA vaccines and numerous clinical trials.Diverse therapeutic applications necessitate tailored design of LNPs.Herein,we outline the principles of LNP design for mRNA delivery,focusing specifically on their effectiveness,targeting capabilities,safety profiles,and nanoparticle stability.Additionally,we present the latest advancements in mRNA-LNP technology.This review aims to elucidate the benefits and design principles of LNP delivery systems for mRNA therapeutics,providing insights into breakthroughs and innovative ideas for further enhancing these advantages.These summaries are dedicated to promoting the broader applications of LNP-mRNA drugs,aiming to advance the treatment of serious diseases in an effective and safe manner.展开更多
which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader...which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader scope for biomarker development.In addition,a potential mode of ICB resistance is tumor-intrinsic mechanisms leading to an immunosuppressive tumor microenvironment(TME).However,the underlying interactive network remains elusive,and the generalizable biomarkers and targeting strategies are still lacking.Here,we uncovered the potential of plasma S100 calcium-binding protein A1(S100A1)for determining ICB efficacy via liquid biopsy of patients with lung cancer.Multiomics and functional studies have suggested that tumor-intrinsic S100A1 expression correlated with an immunologically"cold"TME and resistance to ICB in multiple syngeneic murine tumors and tissue samples from patients with lung cancer.Mechanistic investigations demonstrated that interfering with the tumor-intrinsic S100A1/ubiquitin-specific protease 7/p65/granulocyte-macrophage colony-stimulating factor(GM-CSF)modulatory axis could potentiate an inflamed TME by promoting M1-like macrophage polarization and T cell function.GM-CSF priming was sufficient to enhance the ICB response in tumors with high S100A1 expression in preclinical models.These findings define S100A1 as a potential blood-based biomarker and a novel synergistic target for cancer immunotherapy.展开更多
The integration of nanotechnology with cancer therapy has revolutionized traditional diagnostic and treatment methods,giving rise to the new interdisciplinary field of nano-oncology.With advancements in scientific res...The integration of nanotechnology with cancer therapy has revolutionized traditional diagnostic and treatment methods,giving rise to the new interdisciplinary field of nano-oncology.With advancements in scientific research and ongoing technological innovations,nano-oncology is expected to play an increasingly critical role in future cancer therapies.However,the clinical translation of nanomedicines still faces several challenges,including the interaction of nanoparticles with biological systems,effective accumulation at tumor sites,and the precise fabrication of therapeutic agents.This review focuses on the challenges and future directions in nano-oncology research,with a specific emphasis on multi-stage targeting strategies and the application of artificial intelligence.The aim is to provide insights into the development of individualized nanomedicine approaches and contribute to advancing the field of nano-oncology.展开更多
Cities are central to global climate change mitigation efforts due to their substantial carbon emissions.Effective,evidence-based climate policy requires a detailed understanding of urban carbon metabolism,allowing fo...Cities are central to global climate change mitigation efforts due to their substantial carbon emissions.Effective,evidence-based climate policy requires a detailed understanding of urban carbon metabolism,allowing for targeted mitigation pathways and the accurate evaluation of sustainability.However,a persistent lack of clarity on how carbon flows are distributed spatially and sectorally within cities has hindered tailored climate action,particularly in rapidly developing megacities.Here we map the shifting landscape of carbon emissions in Chinese megacities and show that accountability for these emissions has undergone a profound spatial and sectoral transformation.We found that the primary burden of emission responsibility has moved from production-focused sectors,such as industry and energy generation,to consumption-based end-users,including residential and commercial buildings.This transition is driven by a structural shift in accounting boundaries from direct fossil fuel combustion(Scope 1)to indirect emissions from electricity consumption(Scope 2),fundamentally redistributing carbon liability across urban districts.Our landscape-level framework reveals the hidden carbon dependencies of end-use sectors and provides a model for equitable and effective accounting,enabling the design of region-specific strategies to address the complexities of urban carbon emissions.展开更多
Solid tumors account for more than 60%of all the pediatric malignancies and contribute substantially to the disease burden in China[1].Currently,there are five primary treatment strategies:surgery,radiation therapy,co...Solid tumors account for more than 60%of all the pediatric malignancies and contribute substantially to the disease burden in China[1].Currently,there are five primary treatment strategies:surgery,radiation therapy,conventional chemotherapy,molecular targeted agents and immunotherapy.While the first three methods are nearing their potential limits,the latter two are advancing rapidly,with new approaches continually emerging and resulting in positive clinical outcomes.展开更多
Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional dif...Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.展开更多
文摘Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
文摘HIV-related stigma,discrimination,and other forms of oppression can severely undermine adherence to antiretroviral therapy(ART)among people living with HIV[1].For example,Kerr et al.reveal that perceived discrimination based on sexual orientation in healthcare settings significantly reduces ART adherence[1].This highlights the urgent need for targeted strategies to address stigma,discrimination,and social marginalization,especially within healthcare facilities,to improve HIV care outcomes.
基金study was supported by the National Key Research and Development Program of China(2022YFC2402900)National Natural Science Foundation of China(82470989,52103327)+3 种基金The Joint Funds of the Hunan Provincial Natural Science Foundation(2023JJ60509)The Science and Technology Talent Support Project of the Hunan Provincial Science Popularization Special Project(2023TJ-Z08)Hunan Provincial Innovation Foundation for Postgraduate(2023ZZTS0218)The Postgraduate Inde-pendent Exploration Innovation Fund of the Central South University(2023ZZTS0987)。
文摘Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However,despite some advancements in recent years,no targeted antifibrotic strategies for OSF have been approved;likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined.In this review,we briefly introduce the epidemiology and etiology of OSF.Then,we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors,secretion function,and activation of ECM-producing myofibroblasts.In addition,we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF.Finally,we summarize strategies to interrupt key mechanisms that cause OSF,including modulation of the ECM,inhibition of inflammation,improvement of vascular disturbance.This review will provide potential routes for developing novel anti-OSF therapeutics.
基金supported by Gansu Provincial Science and Technology Program Project(No.23JRRA868)Lanzhou Municipal Talent Innovation and Entrepreneurship Project(No.2019-RC-103)。
文摘In response to the problems of low sampling efficiency,strong randomness of sampling points,and the tortuous shape of the planned path in the traditional rapidly-exploring random tree(RRT)algorithm and bidirectional RRT algorithm used for unmanned aerial vehicle(UAV)path planning in complex environments,an improved bidirectional RRT algorithm was proposed.The algorithm firstly adopted a goal-oriented strategy to guide the sampling points towards the target point,and then the artificial potential field acted on the random tree nodes to avoid collision with obstacles and reduced the length of the search path,and the random tree node growth also combined the UAV’s own flight constraints,and by combining the triangulation method to remove the redundant node strategy and the third-order B-spline curve for the smoothing of the trajectory,the planned path was better.The planned paths were more optimized.Finally,the simulation experiments in complex and dynamic environments showed that the algorithm effectively improved the speed of trajectory planning and shortened the length of the trajectory,and could generate a safe,smooth and fast trajectory in complex environments,which could be applied to online trajectory planning.
基金supported by NIH grant R01 GM084020the Japan National Institute of Radiological Sciences International Open Laboratory Program
文摘Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.
基金supported by China NSF(61572222, 61272405, 61272033, 61272451, 61472121)Fundamental Research Funds for the Central Universities and the open research fund of Zhejiang Provincial Key Lab of Data StorageTransmission Technology, Hangzhou Dianzi University(No. 201301)
文摘Network structures and human behaviors are considered as two important factors in virus defense currently. However, due to ignorance of network security, normal users usually take simple activities, such as reinstalling computer system, or using the computer recovery system to clear virus. How system recovery influences virus spreading is not taken into consideration currently. In this paper, a new virus propagation model considering the system recovery is proposed first, and then in its steady-state analysis, the virus propagation steady time and steady states are deduced. Experiment results show that models considering system recovery can effectively restrain virus propagation. Furthermore, algorithm with system recovery in BA scale-free network is proposed. Simulation result turns out that target immunization strategy with system recovery works better than traditional ones in BA network.
文摘Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer.Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells.Inhibiting tumor cell cholesterol uptake or biosynthesis pathways,through the modulation of receptors and enzymes such as liver X receptor and sterolregulatory element binding protein 2,effectively restrains lung tumor growth.Similarly,promoting cholesterol excretion yields comparable effects.Cholesterol metabolites,including oxysterols and isoprenoids,play a crucial role in regulating cholesterol metabolism within tumor cells,consequently impacting cancer progression.In lung cancer patients,both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth,proliferation,and metastasis.The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells,B cells,macrophages,myeloid-derived suppressor cells,among others.Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments.Statins,targeting the cholesterol biosynthesis pathway,are widely employed in lung cancer treatment,either as standalone agents or in combination with other drugs.Additionally,drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer.In this review,we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.
基金supported by the National Natural Science Foundation of China(No.62202143)Key Research and Promotion Projects of Henan Province(Nos.232102240023,232102210063,222102210040).
文摘Multi-object tracking(MOT)has seen rapid improvements in recent years.However,frequent occlusion remains a significant challenge in MOT,as it can cause targets to become smaller or disappear entirely,resulting in lowquality targets,leading to trajectory interruptions and reduced tracking performance.Different from some existing methods,which discarded the low-quality targets or ignored low-quality target attributes.LQTTrack,with a lowquality association strategy(LQA),is proposed to pay more attention to low-quality targets.In the association scheme of LQTTrack,firstly,multi-scale feature fusion of FPN(MSFF-FPN)is utilized to enrich the feature information and assist in subsequent data association.Secondly,the normalized Wasserstein distance(NWD)is integrated to replace the original Inter over Union(IoU),thus overcoming the limitations of the traditional IoUbased methods that are sensitive to low-quality targets with small sizes and enhancing the robustness of low-quality target tracking.Moreover,the third association stage is proposed to improve the matching between the current frame’s low-quality targets and previously interrupted trajectories from earlier frames to reduce the problem of track fragmentation or error tracking,thereby increasing the association success rate and improving overall multi-object tracking performance.Extensive experimental results demonstrate the competitive performance of LQTTrack on benchmark datasets(MOT17,MOT20,and DanceTrack).
文摘Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.
文摘The reasonable marketing orientation is related to the survival and the development of the enterprises. According to the disadvantages and superiority of the middle and small sized enterprises of our country, this paper analyzes the new thought about the marketing orientation from the aspects of marketing product orientation, marketing way orientation, marketing target orientation, marketing strategy orientation and marketing idea orientation. It has great theoretical and practical significance.
基金supported by the National Natural Science Foundation of China(82088102)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-064)+5 种基金Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Key Discipline Construction Project(2023-2025)of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(GWVI-11.1-35)Shanghai Clinical Research Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital System Diseases Research Center(2022ZZ01012)Shanghai Frontiers Science Research Center of Reproduction and Development,the Shenzhen portion of the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone(program grant#HZQSWS-KCCYB2024031)China Postdoctoral Science Foundation under Grant Number 2025M782263。
文摘Sperm motility and morphology are indispensable for sperm-egg interaction and successful fertilization.However,the RNA splicing mechanisms in an m6A-dependent manner regulating spermiogenesis-related genes remain poorly defined,and targeted therapy strategies to restore impaired sperm motility and morphology are lacking.In this study,we identify heterogeneous nuclear ribonucleoprotein R(hnRNPR)as a critical m6A-dependent splicing mediator.Pathogenic mutations in HNRNPR cause sperm motility decline,morphological abnormality,and male infertility in both humans and mice.Mechanistically,Hnrnpr mutation disrupts m6A-dependent splicing of Skap2 pre-mRNA,thus impairing cytoskeletal structure and mitochondrial organization in sperm.Consistently,specific knockout of Skap2 in male germ cells displays sperm abnormalities,which phenocopy those observed in humans and mice with Hnrnpr mutants,unveiling a functional hnRNPR-SKAP2 axis.Leveraging these insights,we developed a therapeutic strategy to restore sperm motility and morphology,relying on extracellular vesicle-mediated SKAP2 delivery to enter the efferent ductules of the testicles,which could promote sperm cytoskeletal remodeling and mitochondrial organization.Notably,the co-culture of extracellular vesicle SKAP2 with human and mouse sperms also significantly enhanced the sperm motility.Altogether,these findings identify hnRNPR as a pivotal regulator of m6A-mediated Skap2 splicing during spermiogenesis and highlight extracellular vesicle SKAP2 as a promising therapeutic target for poor sperm quality and male infertility.
基金supported by the National Natural Science Foundation of China(81872810)Program for HUST Academic Frontier Youth Team(2018QYTD13,China)the Fundamental Research Funds for the Central Universities(2018KFYYXJJ019 and 2019KFYRCPY049,China)。
文摘Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coronavirus disease 2019(COVID-19)have been encountered with a high risk of ARDS,underscoring the urgency for exploiting effective therapy.However,proper medications for ARDS are still lacking due to poor pharmacokinetics,non-specific side effects,inability to surmount pulmonary barrier,and inadequate management of heterogeneity.The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery.Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy,which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment.Through passive,active,or physicochemical targeting,nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment,thereby showing good therapeutic activity and reduced toxicity.This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy,highlights the strategies for targeted treatment of lung inflammation,presents the innovative drug delivery systems,and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.
基金Zhejiang University Startup PackageZhejiang Provincial Natural Science Foundation of China,Grant/Award Number:LZ23H180003+2 种基金National Natural Science Foundation of China,Grant/AwardNumbers:32471375,22205201National Center of Technology Innovation for Biopharmaceuticals,Grant/Award Number:NCTIB2022HS01013National Natural Science Fund for Excellent Young Scientists Fund Program。
文摘mRNA therapeutics have significantly evolved within the life sciences,particularly in applications such as vaccines,tumor immunotherapy,protein replacement,gene editing,and monoclonal antibody therapy.To fully realize the potential of mRNA drugs and mitigate the adverse effects,substantial vector materials have been developed for delivery of these pharmaceutical agents.Lipid nanoparticles(LNPs)represent the most clinically advanced mRNA carriers,recognized by U.S.Food and Drug Administration approved mRNA vaccines and numerous clinical trials.Diverse therapeutic applications necessitate tailored design of LNPs.Herein,we outline the principles of LNP design for mRNA delivery,focusing specifically on their effectiveness,targeting capabilities,safety profiles,and nanoparticle stability.Additionally,we present the latest advancements in mRNA-LNP technology.This review aims to elucidate the benefits and design principles of LNP delivery systems for mRNA therapeutics,providing insights into breakthroughs and innovative ideas for further enhancing these advantages.These summaries are dedicated to promoting the broader applications of LNP-mRNA drugs,aiming to advance the treatment of serious diseases in an effective and safe manner.
基金the following funding sources:National Key R&D Program of China(2022YFC2505000)NSFC general program(82272796)+3 种基金NSFC general program(8197112364)NSFC special program(82241229)CAMS Innovation Fund for Medical Sciences(CIFMS 2022-12M-1-009)Heilongjiang Province"Unveiling the Leader"Science and Technology Research Project(2022ZXJ03CO).
文摘which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader scope for biomarker development.In addition,a potential mode of ICB resistance is tumor-intrinsic mechanisms leading to an immunosuppressive tumor microenvironment(TME).However,the underlying interactive network remains elusive,and the generalizable biomarkers and targeting strategies are still lacking.Here,we uncovered the potential of plasma S100 calcium-binding protein A1(S100A1)for determining ICB efficacy via liquid biopsy of patients with lung cancer.Multiomics and functional studies have suggested that tumor-intrinsic S100A1 expression correlated with an immunologically"cold"TME and resistance to ICB in multiple syngeneic murine tumors and tissue samples from patients with lung cancer.Mechanistic investigations demonstrated that interfering with the tumor-intrinsic S100A1/ubiquitin-specific protease 7/p65/granulocyte-macrophage colony-stimulating factor(GM-CSF)modulatory axis could potentiate an inflamed TME by promoting M1-like macrophage polarization and T cell function.GM-CSF priming was sufficient to enhance the ICB response in tumors with high S100A1 expression in preclinical models.These findings define S100A1 as a potential blood-based biomarker and a novel synergistic target for cancer immunotherapy.
文摘The integration of nanotechnology with cancer therapy has revolutionized traditional diagnostic and treatment methods,giving rise to the new interdisciplinary field of nano-oncology.With advancements in scientific research and ongoing technological innovations,nano-oncology is expected to play an increasingly critical role in future cancer therapies.However,the clinical translation of nanomedicines still faces several challenges,including the interaction of nanoparticles with biological systems,effective accumulation at tumor sites,and the precise fabrication of therapeutic agents.This review focuses on the challenges and future directions in nano-oncology research,with a specific emphasis on multi-stage targeting strategies and the application of artificial intelligence.The aim is to provide insights into the development of individualized nanomedicine approaches and contribute to advancing the field of nano-oncology.
基金supported by the Shenzhen Science,Technology,and Innovation Commission(Grant No.WDZC20220810110301001001)。
文摘Cities are central to global climate change mitigation efforts due to their substantial carbon emissions.Effective,evidence-based climate policy requires a detailed understanding of urban carbon metabolism,allowing for targeted mitigation pathways and the accurate evaluation of sustainability.However,a persistent lack of clarity on how carbon flows are distributed spatially and sectorally within cities has hindered tailored climate action,particularly in rapidly developing megacities.Here we map the shifting landscape of carbon emissions in Chinese megacities and show that accountability for these emissions has undergone a profound spatial and sectoral transformation.We found that the primary burden of emission responsibility has moved from production-focused sectors,such as industry and energy generation,to consumption-based end-users,including residential and commercial buildings.This transition is driven by a structural shift in accounting boundaries from direct fossil fuel combustion(Scope 1)to indirect emissions from electricity consumption(Scope 2),fundamentally redistributing carbon liability across urban districts.Our landscape-level framework reveals the hidden carbon dependencies of end-use sectors and provides a model for equitable and effective accounting,enabling the design of region-specific strategies to address the complexities of urban carbon emissions.
基金support from the Natural Science Foundation of China(No.81470304)the Key Project of Zhejiang Provincial Science and Technology Department(No.2019C03032).
文摘Solid tumors account for more than 60%of all the pediatric malignancies and contribute substantially to the disease burden in China[1].Currently,there are five primary treatment strategies:surgery,radiation therapy,conventional chemotherapy,molecular targeted agents and immunotherapy.While the first three methods are nearing their potential limits,the latter two are advancing rapidly,with new approaches continually emerging and resulting in positive clinical outcomes.
基金supported by the Drug Innovation Major Project(2018ZX09711001-002-005,China)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2017-I2M-1-011,China)+1 种基金National Natural Science Foundation of China(No.82073778,China)Fundamental Research Funds for the Central Public Welfare Research Institutes(2018PT35002,China)
文摘Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.
