Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on choli...Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.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
Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvas...Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvasive and real-time visualization of important biomolecules or biological events, and it has witnessed major advances in the field of imaging in vitro and in vivo. In this review, we present a survey of common approaches and tactics for enhanced targetability, response rate, and photostability in bioimaging applications. Recently developed and representative examples are illustrated on the cellular and tissue levels.展开更多
In this article,our nonlinear theory and technology for reducing the uncertainties of high-impact ocean‒atmosphere event predictions,with the conditional nonlinear optimal perturbation(CNOP)method as its core,are revi...In this article,our nonlinear theory and technology for reducing the uncertainties of high-impact ocean‒atmosphere event predictions,with the conditional nonlinear optimal perturbation(CNOP)method as its core,are reviewed,and the“spring predictability barrier”problem for El Nino‒Southern Oscillation events and targeted observation issues for tropical cyclone forecasts are taken as two representative examples.Nonlinear theory reveals that initial errors of particular spatial structures,environmental conditions,and nonlinear processes contribute to significant prediction errors,whereas nonlinear technology provides a pioneering approach for reducing observational and forecast errors via targeted observations through the application of the CNOP method.Follow-up research further validates the scientific rigor of the theory in revealing the nonlinear mechanism of significant prediction errors,and relevant practical field campaigns for targeted observations verify the effectiveness of the technology in reducing prediction uncertainties.The CNOP method has achieved international recognition;furthermore,its applications further extend to ensemble forecasts for weather and climate and further enrich the nonlinear technology for reducing prediction uncertainties.It is expected that this nonlinear theory and technology will play a considerably important role in reducing prediction uncertainties for high-impact weather and climate events.展开更多
Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the ...Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.展开更多
Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medic...Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.展开更多
Neutrophils have emerged as key players in tumor progression and are often associated with poor prognosis.Despite ongoing efforts to target neutrophil functions in cancer,therapeutic success has been limited.In this s...Neutrophils have emerged as key players in tumor progression and are often associated with poor prognosis.Despite ongoing efforts to target neutrophil functions in cancer,therapeutic success has been limited.In this study,we addressed the possibility of blocking STAT3 signaling in neutrophils as a targeted therapeutic intervention in cancer.Conditional deletion of Stat3 in a neutrophil-specific manner(Ly6GcreStat3fl/fl mice)significantly impaired tumor growth and metastasis in mice.Neutrophils isolated from these mice exhibited a strong antitumoral phenotype,with increased MHCII,CD80/86 and ICAM-1 expression.Immune profiling of tumors and tumor-draining lymph nodes of these mice revealed significant enrichment of CD8^(+)T cells(granzymeB^(hi),perforin^(hi) and IFN-γ^(hi))with strong cytotoxic activity.To further translate these findings to human settings,we blocked STAT3 signaling in cancer patient neutrophils via the small molecule in^(hi)bitor LLL12 and assessed its effects on patient-derived tumor explants.In agreement with the in vivo mouse data,we observed the expansion and activation of cytotoxic CD8^(+)T cells in such explants.To test the therapeutic applicability of STAT3 targeting,we utilized myeloid cell-selective STAT3 antisense oligonucleotide(CpG-STAT3ASO)to target neutrophils in vivo in tumor-bearing mice.Consistent with previous results,neutrophil-specific STAT3 knockdown impaired tumor growth and enhanced cytotoxic T cell activity in the tumors and tumor-draining lymph nodes of treated mice.These findings highlight STAT3 signaling as a deleterious pathway supporting the protumoral activity of neutrophils and suggest that neutrophil-targeted STAT3 in^(hi)bition is a promising opportunity for cancer immunotherapy,providing novel insights into targeted therapeutic avenues.展开更多
Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor c...Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.展开更多
An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyram...An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyramid network(FPN)structure of the original YOLOv8 mode is replaced by the generalized-FPN(GFPN)structure in GiraffeDet to realize the"cross-layer"and"cross-scale"adaptive feature fusion,to enrich the semantic information and spatial information on the feature map to improve the target detection ability of the model.Secondly,a pyramid-pool module of multi atrous spatial pyramid pooling(MASPP)is designed by using the idea of atrous convolution and feature pyramid structure to extract multi-scale features,so as to improve the processing ability of the model for multi-scale objects.The experimental results show that the detection accuracy of the improved YOLOv8 model on DIOR dataset is 92%and mean average precision(mAP)is 87.9%,respectively 3.5%and 1.7%higher than those of the original model.It is proved the detection and classification ability of the proposed model on multi-dimensional optical remote sensing target has been improved.展开更多
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.展开更多
Tomato plant diseases often first manifest on the leaves,making the detection of tomato leaf diseases particularly crucial for the tomato cultivation industry.However,conventional deep learning models face challenges ...Tomato plant diseases often first manifest on the leaves,making the detection of tomato leaf diseases particularly crucial for the tomato cultivation industry.However,conventional deep learning models face challenges such as large model sizes and slow detection speeds when deployed on resource-constrained platforms and agricultural machinery.This paper proposes a lightweight model for detecting tomato leaf diseases,named LT-YOLO,based on the YOLOv8n architecture.First,we enhance the C2f module into a RepViT Block(RVB)with decoupled token and channel mixers to reduce the cost of feature extraction.Next,we incorporate a novel Efficient Multi-Scale Attention(EMA)mechanism in the deeper layers of the backbone to improve detection of critical disease features.Additionally,we design a lightweight detection head,LT-Detect,using Partial Convolution(PConv)to significantly reduce the classification and localization costs during detection.Finally,we introduce a Receptive Field Block(RFB)in the shallow layers of the backbone to expand the model’s receptive field,enabling effective detection of diseases at various scales.The improved model reduces the number of parameters by 43%and the computational load by 50%.Additionally,it achieves a mean Average Precision(mAP)of 90.9%on a publicly available dataset containing 3641 images of tomato leaf diseases,with only a 0.7%decrease compared to the baseline model.This demonstrates that the model maintains excellent accuracy while being lightweight,making it suitable for rapid detection of tomato leaf diseases.展开更多
Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restor...Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restore blood flow as early as possible,while the pathological mechanism of reperfusion injury after restoring blood flow is complex,involving oxidative stress,calcium overload,and inflammatory response.In recent years,more and more studies have found that ferroptosis mediation is involved in the occurrence and development of cerebral ischemia-reperfusion injury.This paper elaborates on the concept,mechanisms,and regulation of ferroptosis,detailing its role in cerebral ischemia-reperfusion injury and potential inhibition strategies.The aim is to deepen the understanding of ferroptosis in this pathological process and provide insights for possible targeted therapies.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Unmanned aerial vehicle(UAV)imagery poses significant challenges for object detection due to extreme scale variations,high-density small targets(68%in VisDrone dataset),and complex backgrounds.While YOLO-series models...Unmanned aerial vehicle(UAV)imagery poses significant challenges for object detection due to extreme scale variations,high-density small targets(68%in VisDrone dataset),and complex backgrounds.While YOLO-series models achieve speed-accuracy trade-offs via fixed convolution kernels and manual feature fusion,their rigid architectures struggle with multi-scale adaptability,as exemplified by YOLOv8n’s 36.4%mAP and 13.9%small-object AP on VisDrone2019.This paper presents YOLO-LE,a lightweight framework addressing these limitations through three novel designs:(1)We introduce the C2f-Dy and LDown modules to enhance the backbone’s sensitivity to small-object features while reducing backbone parameters,thereby improving model efficiency.(2)An adaptive feature fusion module is designed to dynamically integrate multi-scale feature maps,optimizing the neck structure,reducing neck complexity,and enhancing overall model performance.(3)We replace the original loss function with a distributed focal loss and incorporate a lightweight self-attention mechanism to improve small-object recognition and bounding box regression accuracy.Experimental results demonstrate that YOLO-LE achieves 39.9%mAP@0.5 on VisDrone2019,representing a 9.6%improvement over YOLOv8n,while maintaining 8.5 GFLOPs computational efficiency.This provides an efficient solution for UAV object detection in complex scenarios.展开更多
The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secr...The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.展开更多
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.82271214(to ZY)the Natural Science Foundation of Hubei Province of China,No.2022CFB109(to ZY)。
文摘Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
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.
基金supported by National Natural Science Foundation of China for Science Center Program (21788102)National Key Research and Development Program (2016YFA0200300)+1 种基金Natural Science Foundation of China (21636002)National Postdoctoral Program for Innovative Talents (BX201700075)
文摘Analyses of the physiology and pathology of active biochemical species in their native contexts are critical for early diagnosis and therapy. Optical imaging has emerged as one of the promising modalities for noninvasive and real-time visualization of important biomolecules or biological events, and it has witnessed major advances in the field of imaging in vitro and in vivo. In this review, we present a survey of common approaches and tactics for enhanced targetability, response rate, and photostability in bioimaging applications. Recently developed and representative examples are illustrated on the cellular and tissue levels.
基金sponsored by the National Natural Science Foun-dation of China(Grant No.42330111).
文摘In this article,our nonlinear theory and technology for reducing the uncertainties of high-impact ocean‒atmosphere event predictions,with the conditional nonlinear optimal perturbation(CNOP)method as its core,are reviewed,and the“spring predictability barrier”problem for El Nino‒Southern Oscillation events and targeted observation issues for tropical cyclone forecasts are taken as two representative examples.Nonlinear theory reveals that initial errors of particular spatial structures,environmental conditions,and nonlinear processes contribute to significant prediction errors,whereas nonlinear technology provides a pioneering approach for reducing observational and forecast errors via targeted observations through the application of the CNOP method.Follow-up research further validates the scientific rigor of the theory in revealing the nonlinear mechanism of significant prediction errors,and relevant practical field campaigns for targeted observations verify the effectiveness of the technology in reducing prediction uncertainties.The CNOP method has achieved international recognition;furthermore,its applications further extend to ensemble forecasts for weather and climate and further enrich the nonlinear technology for reducing prediction uncertainties.It is expected that this nonlinear theory and technology will play a considerably important role in reducing prediction uncertainties for high-impact weather and climate events.
基金supported by the National Natural Science Foundations of China(Grant No.:82204584)Liaoning Provincial Science and Technology Projects,China(Project No.:2021JH1/10400055).
文摘Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
基金Supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A00806High Level Chinese Medical Hospital Promotion Project,No.HLCMHPP2023086the Fundamental Research Funds for the Central Public Welfare Research Institutes,No.ZZ17-XRZ-041.
文摘Chronic atrophic gastritis(CAG)is an important stage of precancerous lesions of gastric cancer.Effective treatment and regulation of CAG are essential to prevent its progression to malignancy.Traditional Chinese medicine(TCM)has shown multi-targeted efficacy in CAG treatment,with advantages in enhancing gastric mucosal barrier defense,improving microcirculation,modulating inflammatory and immune responses,and promoting lesion healing,etc.Clinical studies and meta-analyses indicate that TCM provides significant benefits,with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation,antioxidation,and regulation of cellular proliferation and apoptosis,etc.Finally,it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards,and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
基金support from the Open Access Publication Fund of the University of Duisburg-Essensupported by the Deutsche Forschungsgemeinschaft(DFG/JA-2461/7-1)+1 种基金CRC TRR332 project A05 to JJthe Stiftung Tumorforschung Kopf-Hals to CK.
文摘Neutrophils have emerged as key players in tumor progression and are often associated with poor prognosis.Despite ongoing efforts to target neutrophil functions in cancer,therapeutic success has been limited.In this study,we addressed the possibility of blocking STAT3 signaling in neutrophils as a targeted therapeutic intervention in cancer.Conditional deletion of Stat3 in a neutrophil-specific manner(Ly6GcreStat3fl/fl mice)significantly impaired tumor growth and metastasis in mice.Neutrophils isolated from these mice exhibited a strong antitumoral phenotype,with increased MHCII,CD80/86 and ICAM-1 expression.Immune profiling of tumors and tumor-draining lymph nodes of these mice revealed significant enrichment of CD8^(+)T cells(granzymeB^(hi),perforin^(hi) and IFN-γ^(hi))with strong cytotoxic activity.To further translate these findings to human settings,we blocked STAT3 signaling in cancer patient neutrophils via the small molecule in^(hi)bitor LLL12 and assessed its effects on patient-derived tumor explants.In agreement with the in vivo mouse data,we observed the expansion and activation of cytotoxic CD8^(+)T cells in such explants.To test the therapeutic applicability of STAT3 targeting,we utilized myeloid cell-selective STAT3 antisense oligonucleotide(CpG-STAT3ASO)to target neutrophils in vivo in tumor-bearing mice.Consistent with previous results,neutrophil-specific STAT3 knockdown impaired tumor growth and enhanced cytotoxic T cell activity in the tumors and tumor-draining lymph nodes of treated mice.These findings highlight STAT3 signaling as a deleterious pathway supporting the protumoral activity of neutrophils and suggest that neutrophil-targeted STAT3 in^(hi)bition is a promising opportunity for cancer immunotherapy,providing novel insights into targeted therapeutic avenues.
文摘Peripheral immunity forms the foundation of tumor immunity,while tumor immunity represents a more refined adaptation of peripheral immune responses.The tumor microenvironment(TME),a localized niche surrounding tumor cells,is inherently immunosuppressive(1,2).Effective tumor therapy necessitates the dismantling of this microenvironment,aiming to eradicate tumors from the host system.
基金supported by the National Natural Science Foundation of China(No.62241109)the Tianjin Science and Technology Commissioner Project(No.20YDTPJC01110)。
文摘An improved model based on you only look once version 8(YOLOv8)is proposed to solve the problem of low detection accuracy due to the diversity of object sizes in optical remote sensing images.Firstly,the feature pyramid network(FPN)structure of the original YOLOv8 mode is replaced by the generalized-FPN(GFPN)structure in GiraffeDet to realize the"cross-layer"and"cross-scale"adaptive feature fusion,to enrich the semantic information and spatial information on the feature map to improve the target detection ability of the model.Secondly,a pyramid-pool module of multi atrous spatial pyramid pooling(MASPP)is designed by using the idea of atrous convolution and feature pyramid structure to extract multi-scale features,so as to improve the processing ability of the model for multi-scale objects.The experimental results show that the detection accuracy of the improved YOLOv8 model on DIOR dataset is 92%and mean average precision(mAP)is 87.9%,respectively 3.5%and 1.7%higher than those of the original model.It is proved the detection and classification ability of the proposed model on multi-dimensional optical remote sensing target has been improved.
基金supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金supported by the National Natural Science Foundation of China(No.82170326 and No.82470328 to Y.D.,No.82100339 to Q.D.).
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.
文摘Tomato plant diseases often first manifest on the leaves,making the detection of tomato leaf diseases particularly crucial for the tomato cultivation industry.However,conventional deep learning models face challenges such as large model sizes and slow detection speeds when deployed on resource-constrained platforms and agricultural machinery.This paper proposes a lightweight model for detecting tomato leaf diseases,named LT-YOLO,based on the YOLOv8n architecture.First,we enhance the C2f module into a RepViT Block(RVB)with decoupled token and channel mixers to reduce the cost of feature extraction.Next,we incorporate a novel Efficient Multi-Scale Attention(EMA)mechanism in the deeper layers of the backbone to improve detection of critical disease features.Additionally,we design a lightweight detection head,LT-Detect,using Partial Convolution(PConv)to significantly reduce the classification and localization costs during detection.Finally,we introduce a Receptive Field Block(RFB)in the shallow layers of the backbone to expand the model’s receptive field,enabling effective detection of diseases at various scales.The improved model reduces the number of parameters by 43%and the computational load by 50%.Additionally,it achieves a mean Average Precision(mAP)of 90.9%on a publicly available dataset containing 3641 images of tomato leaf diseases,with only a 0.7%decrease compared to the baseline model.This demonstrates that the model maintains excellent accuracy while being lightweight,making it suitable for rapid detection of tomato leaf diseases.
基金Natural Science Basic Research Program of Shaanxi Province(Project No.:2021JM-554)。
文摘Ferroptosis is a novel form of non-apoptotic cell death that has been widely studied in recent years and is involved in a variety of pathophysiological processes.The core treatment goal of ischemic stroke is to restore blood flow as early as possible,while the pathological mechanism of reperfusion injury after restoring blood flow is complex,involving oxidative stress,calcium overload,and inflammatory response.In recent years,more and more studies have found that ferroptosis mediation is involved in the occurrence and development of cerebral ischemia-reperfusion injury.This paper elaborates on the concept,mechanisms,and regulation of ferroptosis,detailing its role in cerebral ischemia-reperfusion injury and potential inhibition strategies.The aim is to deepen the understanding of ferroptosis in this pathological process and provide insights for possible targeted therapies.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
文摘Unmanned aerial vehicle(UAV)imagery poses significant challenges for object detection due to extreme scale variations,high-density small targets(68%in VisDrone dataset),and complex backgrounds.While YOLO-series models achieve speed-accuracy trade-offs via fixed convolution kernels and manual feature fusion,their rigid architectures struggle with multi-scale adaptability,as exemplified by YOLOv8n’s 36.4%mAP and 13.9%small-object AP on VisDrone2019.This paper presents YOLO-LE,a lightweight framework addressing these limitations through three novel designs:(1)We introduce the C2f-Dy and LDown modules to enhance the backbone’s sensitivity to small-object features while reducing backbone parameters,thereby improving model efficiency.(2)An adaptive feature fusion module is designed to dynamically integrate multi-scale feature maps,optimizing the neck structure,reducing neck complexity,and enhancing overall model performance.(3)We replace the original loss function with a distributed focal loss and incorporate a lightweight self-attention mechanism to improve small-object recognition and bounding box regression accuracy.Experimental results demonstrate that YOLO-LE achieves 39.9%mAP@0.5 on VisDrone2019,representing a 9.6%improvement over YOLOv8n,while maintaining 8.5 GFLOPs computational efficiency.This provides an efficient solution for UAV object detection in complex scenarios.
基金the National Natural Science Foundation of China(82471593 to J.M.32330047 and 31930057 to F.W.+2 种基金and 82071970 to Y.W.and 82072506 to Y.L.)the Science Fund for Distinguished Young Scholars of Hubei Province(2023AFA109 to Y.W.)Hubei Provincial Natural Science Foundation of China(2024AFB963 to Q.R.).
文摘The muscular system plays a critical role in the human body by governing skeletal movement,cardiovascular function,and the activities of digestive organs.Additionally,muscle tissues serve an endocrine function by secreting myogenic cytokines,thereby regulating metabolism throughout the entire body.Maintaining muscle function requires iron homeostasis.Recent studies suggest that disruptions in iron metabolism and ferroptosis,a form of iron-dependent cell death,are essential contributors to the progression of a wide range of muscle diseases and disorders,including sarcopenia,cardiomyopathy,and amyotrophic lateral sclerosis.Thus,a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention.This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury,as well as associated muscle diseases and disorders.Moreover,we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders.Finally,we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
