Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using K...We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using Ka time-resolved imaging,it is found that in the case of massive targets,the hot-electron generation follows the laser pulse intensity with a short delay needed for favorable plasma formation.Conversely,a significant delay in the x-ray emission compared with the laser pulse intensity profile is observed in the case of thin targets.Theoretical analysis and numerical simulations suggest that this is related to radiation preheating of the foil and the increase in hot-electron lifetime in a hot expanding plasma.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
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiolo...Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiology is multifactorial,involving tobacco use,alcohol consumption,and human papillomavirus(HPV)infection.Oral leukoplakia and erythroplakia are the main precancerous lesions lesions,with oral leukoplakia being the most common.Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways.Post-translational modifications(such as ubiquitination and deubiquitination)play key roles in regulating these pathways by controlling protein stability and activity.Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways.The ubiquitination/deubiquitination process mainly involves E3 ligases(E3s)that catalyze substrate ubiquitination,deubiquitinating enzymes(DUBs)that remove ubiquitin chains,and the 26S proteasome complex that degrades ubiquitinated substrates.Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumorrelated proteins,thereby driving OSCC initiation and progression.Therefore,understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components.Here,we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway,Wnt/β-catenin pathway,Hippo pathway,and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways,along with potential drug targets.PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70%of OSCC cases.It is modulated by E3s(e.g.,FBXW7 and NEDD4)and DUBs(e.g.,USP7 and USP10):FBXW7 and USP10 inhibit signaling,while NEDD4 and USP7 potentiate it.Aberrant activation of the Wnt/β-catenin pathway leads toβ-catenin nuclear translocation and induction of cell proliferation.This pathway is modulated by E3s(e.g.,c-Cbl and RNF43)and DUBs(e.g.,USP9X and USP20):c-Cbl and RNF43 inhibit signaling,while USP9X and USP20 potentiate it.Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis.This pathway is modulated by E3s(e.g.,CRL4^(DCAF1) and SIAH2)and DUBs(e.g.,USP1 and USP21):CRL4^(DCAF1) and SIAH2 inhibit signaling,while USP1 and USP21 potentiate it.Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance.This pathway is modulated by E3s(e.g.,TRAF6 and LUBAC)and DUBs(e.g.,A20 and CYLD):A20 and CYLD inhibit signaling,while TRAF6 and LUBAC potentiate it.Targeting these E3s and DUBs provides directions for OSCC drug research.Small-molecule inhibitors such as YCH2823(a USP7 inhibitor),GSK2643943A(a USP20 inhibitor),and HOIPIN-8(a LUBAC inhibitor)have shown promising antitumor activity in preclinical models;PROTAC molecules,by binding to surface sites of target proteins and recruiting E3s,achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors,for example,PU7-1-mediated USP7 degradation,offering new strategies to overcome traditional drug limitations.Currently,NX-1607(a Cbl-b inhibitor)has entered phase I clinical trials,with preliminary results confirming its safety and antitumor activity.Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.展开更多
This article summarizes recent advances in the understanding of RNA-binding proteins(RBPs),with a focus on their roles in exercise-induced mRNA regulation and their implications for schizophrenia(SZ).RBPs are critical...This article summarizes recent advances in the understanding of RNA-binding proteins(RBPs),with a focus on their roles in exercise-induced mRNA regulation and their implications for schizophrenia(SZ).RBPs are critical regulators of mRNA stability,splicing,transport,translation,and degradation,directly influencing gene expression through sequence-and structure-specific binding.In the nervous system,RBPs sustain synaptic plasticity,neural development,and neuronal homeostasis.Emerging evidence shows that exercise modulates the expression and activity of RBPs,thereby influencing mRNA translation and neurotransmitter signaling,which may underlie its beneficial effects on brain function.Dysregulation of specific RBPs has been identified in SZ,implicating them in disrupted synaptic transmission,impaired plasticity,and neuroinflammation.RBPs involved in memory and emotional regulation show marked dysfunction in SZ patients.Some RBPs have been proposed as potential biomarkers for early diagnosis and treatment monitoring.Moreover,therapeutic modulation of RBPs,through pharmacological or behavioral interventions such as exercise,may restore neuronal function by targeting post-transcriptional gene regulation.Exercise,as a non-invasive modulator of RBP expression,holds promise as an adjunctive strategy in SZ treatment,particularly in early stages.Further research into RBP-mediated pathways may offer novel insights into SZ pathophysiology and inform the development of targeted interventions.展开更多
Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neuro...Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neurological disease in humans.The amyloid cascade hypothesis is a hypothesis on the pathogenesis of AD that suggests that abnormal extracellular aggregation ofβ-amyloid(Aβ)peptides is the main cause of the disease.Although this hypothesis has been found to be convincing,a growing body of evidence suggests that it does not fully explain the pathogenesis of AD.Neuroinflammation is a crucial element in the pathogenesis of AD,as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes associated with innate immune function.This paper will first summarize the impact of microglia-mediated neuroinflammation on AD,exploring the phenotypic changes that follow microglia activation.Secondly,the interactions between microglia,Aβ,microtubule-associated protein,apolipoprotein E and neurons are thoroughly investigated,with particular focus on the interactive mechanisms.Furthermore,the recent progress and prospects of microglia as a diagnostic and therapeutic target for AD are analysed.A review of the literature on the mechanisms regulating MG for AD at home and abroad revealed that acupuncture modulation of microglia could help to delay the progression of AD.This was followed by an extensive discussion of the clinical possibilities and scientific validity of acupuncture treatment for AD,with the aim of providing new insights for acupuncture modulation of MG targeting for the treatment of AD.展开更多
This study combines ground penetrating radar(GPR)and convolutional neural networks for the intelligent detection of underground road targets.The target location was realized using a gradient-class activation map(Grad-...This study combines ground penetrating radar(GPR)and convolutional neural networks for the intelligent detection of underground road targets.The target location was realized using a gradient-class activation map(Grad-CAM).First,GPR technology was used to detect roads and obtain radar images.This study constructs a radar image dataset containing 3000 underground road radar targets,such as underground pipelines and holes.Based on the dataset,a ResNet50 network was used to classify and train different underground targets.During training,the accuracy of the training set gradually increases and finally fluctuates approximately 85%.The loss function gradually decreases and falls between 0.2 and 0.3.Finally,targets were located using Grad-CAM.The positioning results of single and multiple targets are consistent with the actual position,indicating that the method can eff ectively realize the intelligent detection of underground targets in GPR.展开更多
Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discusse...Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discussed well in scientific literature.In particular,this dipeptide is well-known for its antioxidant,anti-inflammatory,and anti-aggregation activities.It is of great interest in the context of numerous systemic and neurodegenerative diseases,besides performing important“side activities”such as metal chelation and pH-buffering.Despite a plethora of preclinical and clinical data supporting carnosine’s therapeutic potential,researchers are still searching for new pharmacological targets that better highlight carnosine’s overall multimodal mechanism of action and allow its disease-specific use.The aim of the present mini-review,after quickly summarizing the current knowledge of carnosine biological properties,is to pinpoint the role of some non-canonical factors/pathways positively modulated by this dipeptide,highlighting their perspective role as future pharmacological targets.展开更多
Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical r...Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.展开更多
Pose estimation of spacecraft targets is a key technology for achieving space operation tasks,such as the cleaning of failed satellites and the detection and scanning of non-cooperative targets.This paper reviews the ...Pose estimation of spacecraft targets is a key technology for achieving space operation tasks,such as the cleaning of failed satellites and the detection and scanning of non-cooperative targets.This paper reviews the target pose estimation methods based on image feature extraction and PnP,the target estimation methods based on registration,and the spacecraft target pose estimation methods based on deep learning,and introduces the corresponding research methods.展开更多
An experimental and finite element simulation investigation are conducted to study the deformation patterns of steel targets during the penetration process of tungsten alloy long rods,as well as the influence of stren...An experimental and finite element simulation investigation are conducted to study the deformation patterns of steel targets during the penetration process of tungsten alloy long rods,as well as the influence of strength of the target on the deformation patterns.The experimental results revealed slight mass loss in the first layer of the steel target during the transient entrance phase,with an extremely negligible loss in target mass during the quasi-steady penetration phase.The results of macro-analysis,micro-analysis and simulation show that the eroded target material migrated towards the periphery of the crater,causing an increase in the target's thickness,remained within the target,instead of flowing out of the crater.Therefore,the process of long rods penetrating the metal target is considered as a process of backward extrusion.By combining the backward extrusion theory with energy conservation,a penetration depth model for long rods penetrating a metal target,taking into account both the diameter of the crater and the friction coefficient between the rod and the target,has been established.Although the model is not yet perfect,it innovatively applies the principles of solid mechanics to the study of long rod penetration.Additionally,it takes into account the friction coefficient between the rod and the target during the penetration process.Therefore,this model provides a new research direction for future studies on long rod penetration.展开更多
One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despit...One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.展开更多
Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in...Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.展开更多
Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels r...Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.展开更多
Laser-driven ion acceleration,as produced by interaction of a high-intensity laser with a target,is a growing field of interest.One of the current challenges is to enhance the acceleration process,i.e.,to increase the...Laser-driven ion acceleration,as produced by interaction of a high-intensity laser with a target,is a growing field of interest.One of the current challenges is to enhance the acceleration process,i.e.,to increase the produced ion energy and the ion number and to shape the energy distribution for future applications.In this paper,we investigate the effect of helical coil(HC)targets on the laser-matter interaction process using a 150 TW laser.We demonstrate that HC targets significantly enhance proton acceleration,improving energy bunching and beam focusing and increasing the cutoff energy.For the first time,we extend this analysis to carbon ions,revealing a marked reduction in the number of low-energy carbon ions and the potential for energy bunching and post-acceleration through an optimized HC design.Simulations using the particle-in-cell code SOPHIE confirm the experimental results,providing insights into the current propagation and ion synchronization mechanisms in HCs.Our findings suggest that HC targets can be optimized for multispecies ion acceleration.展开更多
AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)...AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study(GWAS)summary datasets were used in this study.Causal associations between plasma proteins and POAG were identified using summary-data-based MR(SMR)analysis and the heterogeneity in dependent instruments(HEIDI)test.Colocalization analysis was then conducted to assess the genetic associations between these two factors.Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects.Finally,protein-protein interactions(PPI)were studied,and the Drug-Gene Interaction Database(DGIDb)was used to identify associations between drugs and the identified proteins.RESULTS:Four proteins(SVEP1,TMEM190,ROBO1,and ENPP5)were identified as potential drug targets in this study.Phenome-wide MR analysis showed that SVEP1,ROBO1,and ENPP5 were not associated with adverse effects,while TMEM190 was linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.CONCLUSION:Four plasma proteins—SVEP1,TMEM190,ROBO1,and ENPP5—are identified as potential therapeutic targets for POAG through an MR approach.Phenome-wide MR analysis reveals that SVEP1,ROBO1,and ENPP5 are not associated with adverse effects,while TMEM190 is linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1.These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.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
It is difficult to improve both energy consumption and detection accuracy simultaneously,and even to obtain the trade-off between them,when detecting and tracking moving targets,especially for Underwater Wireless Sens...It is difficult to improve both energy consumption and detection accuracy simultaneously,and even to obtain the trade-off between them,when detecting and tracking moving targets,especially for Underwater Wireless Sensor Networks(UWSNs).To this end,this paper investigates the relationship between the Degree of Target Change(DoTC)and the detection period,as well as the impact of individual nodes.A Hierarchical Detection and Tracking Approach(HDTA)is proposed.Firstly,the network detection period is determined according to DoTC,which reflects the variation of target motion.Secondly,during the network detection period,each detection node calculates its own node detection period based on the detection mutual information.Taking DoTC as pheromone,an ant colony algorithm is proposed to adaptively adjust the network detection period.The simulation results show that the proposed HDTA with the optimizations of network level and node level significantly improves the detection accuracy by 25%and the network energy consumption by 10%simultaneously,compared to the traditional adaptive period detection schemes.展开更多
A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,...A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,enabling the acquisition of full-process data of the fragment scattering process.However,mismatches between camera frame rates and target velocities can lead to long motion blur tails of high-speed fragment targets,resulting in low signal-to-noise ratios and rendering conventional detection algorithms ineffective in dynamic strong interference testing environments.In this study,we propose a detection framework centered on dynamic strong interference disturbance signal separation and suppression.We introduce a mixture Gaussian model constrained under a joint spatialtemporal-transform domain Dirichlet process,combined with total variation regularization to achieve disturbance signal suppression.Experimental results demonstrate that the proposed disturbance suppression method can be integrated with certain conventional motion target detection tasks,enabling adaptation to real-world data to a certain extent.Moreover,we provide a specific implementation of this process,which achieves a detection rate close to 100%with an approximate 0%false alarm rate in multiple sets of real target field test data.This research effectively advances the development of the field of damage parameter testing.展开更多
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
基金funding via EUROfusion Enabling research Project No.AWP21-ENR-01-CEA-02“Advancing Shock Ignition for Direct-Drive Inertial Fusion,”the framework of the EUROfusion Consortium,funded by the European Union via the Euratom Research and Training Programme (Grant Agreement No.101052200-EUROfusion)+2 种基金the Czech Ministry of Education,Youth and Sports (CMEYS) for funding the operation of the PALS facility (Grant No.LM2023068)the EuroHPC Joint Undertaking for awarding access to Karolina at IT4Innovations (VSB-TU),Czechia under Project No.EHPC-REG-2023R02-006(DD-23-157)the Ministry of Education,Youth and Sports of the Czech Republic through e-INFRA CZ (Grant No.ID:90140)
文摘We investigate the spatial and temporal correlations of hot-electron generation in high-intensity laser interaction with massive and thin copper targets under conditions relevant to inertial confinement fusion.Using Ka time-resolved imaging,it is found that in the case of massive targets,the hot-electron generation follows the laser pulse intensity with a short delay needed for favorable plasma formation.Conversely,a significant delay in the x-ray emission compared with the laser pulse intensity profile is observed in the case of thin targets.Theoretical analysis and numerical simulations suggest that this is related to radiation preheating of the foil and the increase in hot-electron lifetime in a hot expanding plasma.
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 grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
文摘Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiology is multifactorial,involving tobacco use,alcohol consumption,and human papillomavirus(HPV)infection.Oral leukoplakia and erythroplakia are the main precancerous lesions lesions,with oral leukoplakia being the most common.Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways.Post-translational modifications(such as ubiquitination and deubiquitination)play key roles in regulating these pathways by controlling protein stability and activity.Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways.The ubiquitination/deubiquitination process mainly involves E3 ligases(E3s)that catalyze substrate ubiquitination,deubiquitinating enzymes(DUBs)that remove ubiquitin chains,and the 26S proteasome complex that degrades ubiquitinated substrates.Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumorrelated proteins,thereby driving OSCC initiation and progression.Therefore,understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components.Here,we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway,Wnt/β-catenin pathway,Hippo pathway,and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways,along with potential drug targets.PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70%of OSCC cases.It is modulated by E3s(e.g.,FBXW7 and NEDD4)and DUBs(e.g.,USP7 and USP10):FBXW7 and USP10 inhibit signaling,while NEDD4 and USP7 potentiate it.Aberrant activation of the Wnt/β-catenin pathway leads toβ-catenin nuclear translocation and induction of cell proliferation.This pathway is modulated by E3s(e.g.,c-Cbl and RNF43)and DUBs(e.g.,USP9X and USP20):c-Cbl and RNF43 inhibit signaling,while USP9X and USP20 potentiate it.Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis.This pathway is modulated by E3s(e.g.,CRL4^(DCAF1) and SIAH2)and DUBs(e.g.,USP1 and USP21):CRL4^(DCAF1) and SIAH2 inhibit signaling,while USP1 and USP21 potentiate it.Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance.This pathway is modulated by E3s(e.g.,TRAF6 and LUBAC)and DUBs(e.g.,A20 and CYLD):A20 and CYLD inhibit signaling,while TRAF6 and LUBAC potentiate it.Targeting these E3s and DUBs provides directions for OSCC drug research.Small-molecule inhibitors such as YCH2823(a USP7 inhibitor),GSK2643943A(a USP20 inhibitor),and HOIPIN-8(a LUBAC inhibitor)have shown promising antitumor activity in preclinical models;PROTAC molecules,by binding to surface sites of target proteins and recruiting E3s,achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors,for example,PU7-1-mediated USP7 degradation,offering new strategies to overcome traditional drug limitations.Currently,NX-1607(a Cbl-b inhibitor)has entered phase I clinical trials,with preliminary results confirming its safety and antitumor activity.Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.
文摘This article summarizes recent advances in the understanding of RNA-binding proteins(RBPs),with a focus on their roles in exercise-induced mRNA regulation and their implications for schizophrenia(SZ).RBPs are critical regulators of mRNA stability,splicing,transport,translation,and degradation,directly influencing gene expression through sequence-and structure-specific binding.In the nervous system,RBPs sustain synaptic plasticity,neural development,and neuronal homeostasis.Emerging evidence shows that exercise modulates the expression and activity of RBPs,thereby influencing mRNA translation and neurotransmitter signaling,which may underlie its beneficial effects on brain function.Dysregulation of specific RBPs has been identified in SZ,implicating them in disrupted synaptic transmission,impaired plasticity,and neuroinflammation.RBPs involved in memory and emotional regulation show marked dysfunction in SZ patients.Some RBPs have been proposed as potential biomarkers for early diagnosis and treatment monitoring.Moreover,therapeutic modulation of RBPs,through pharmacological or behavioral interventions such as exercise,may restore neuronal function by targeting post-transcriptional gene regulation.Exercise,as a non-invasive modulator of RBP expression,holds promise as an adjunctive strategy in SZ treatment,particularly in early stages.Further research into RBP-mediated pathways may offer novel insights into SZ pathophysiology and inform the development of targeted interventions.
文摘Microglia(MG)are immune effector cells in the central nervous system(CNS)and play a pivotal role in the pathogenesis of various CNS diseases.Alzheimer's disease(AD)is defined as a severe chronic degenerative neurological disease in humans.The amyloid cascade hypothesis is a hypothesis on the pathogenesis of AD that suggests that abnormal extracellular aggregation ofβ-amyloid(Aβ)peptides is the main cause of the disease.Although this hypothesis has been found to be convincing,a growing body of evidence suggests that it does not fully explain the pathogenesis of AD.Neuroinflammation is a crucial element in the pathogenesis of AD,as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes associated with innate immune function.This paper will first summarize the impact of microglia-mediated neuroinflammation on AD,exploring the phenotypic changes that follow microglia activation.Secondly,the interactions between microglia,Aβ,microtubule-associated protein,apolipoprotein E and neurons are thoroughly investigated,with particular focus on the interactive mechanisms.Furthermore,the recent progress and prospects of microglia as a diagnostic and therapeutic target for AD are analysed.A review of the literature on the mechanisms regulating MG for AD at home and abroad revealed that acupuncture modulation of microglia could help to delay the progression of AD.This was followed by an extensive discussion of the clinical possibilities and scientific validity of acupuncture treatment for AD,with the aim of providing new insights for acupuncture modulation of MG targeting for the treatment of AD.
基金supported in part by the National Natural Science Fund of China under Grant 52074306in part by the National Key Research and Development Program of China under Grant 2019YFC1805504in part by the Fundamental Research Funds for the Central Universities under Grant 2023JCCXHH02。
文摘This study combines ground penetrating radar(GPR)and convolutional neural networks for the intelligent detection of underground road targets.The target location was realized using a gradient-class activation map(Grad-CAM).First,GPR technology was used to detect roads and obtain radar images.This study constructs a radar image dataset containing 3000 underground road radar targets,such as underground pipelines and holes.Based on the dataset,a ResNet50 network was used to classify and train different underground targets.During training,the accuracy of the training set gradually increases and finally fluctuates approximately 85%.The loss function gradually decreases and falls between 0.2 and 0.3.Finally,targets were located using Grad-CAM.The positioning results of single and multiple targets are consistent with the actual position,indicating that the method can eff ectively realize the intelligent detection of underground targets in GPR.
文摘Carnosine(β-alanyl-L-histidine)is a naturally occurring endogenous peptide widely distributed in excitable tissues,such as the heart and brain.Over the years,several beneficial effects of carnosine have been discussed well in scientific literature.In particular,this dipeptide is well-known for its antioxidant,anti-inflammatory,and anti-aggregation activities.It is of great interest in the context of numerous systemic and neurodegenerative diseases,besides performing important“side activities”such as metal chelation and pH-buffering.Despite a plethora of preclinical and clinical data supporting carnosine’s therapeutic potential,researchers are still searching for new pharmacological targets that better highlight carnosine’s overall multimodal mechanism of action and allow its disease-specific use.The aim of the present mini-review,after quickly summarizing the current knowledge of carnosine biological properties,is to pinpoint the role of some non-canonical factors/pathways positively modulated by this dipeptide,highlighting their perspective role as future pharmacological targets.
基金supported by grants from the National Nat-ural Science Foundation of China(82122010 and 82070659)the National High Level Hospital Clinical Research Funding(2022-PUMCH-E-003)+1 种基金the CAMS Innovation Fund for Medical Science(2022-I2M-1-004)an NIHR Senior Investigator Award。
文摘Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.
文摘Pose estimation of spacecraft targets is a key technology for achieving space operation tasks,such as the cleaning of failed satellites and the detection and scanning of non-cooperative targets.This paper reviews the target pose estimation methods based on image feature extraction and PnP,the target estimation methods based on registration,and the spacecraft target pose estimation methods based on deep learning,and introduces the corresponding research methods.
基金supported by the National Natural Science Foundation of China(Grant Nos.12102201,U2341244).
文摘An experimental and finite element simulation investigation are conducted to study the deformation patterns of steel targets during the penetration process of tungsten alloy long rods,as well as the influence of strength of the target on the deformation patterns.The experimental results revealed slight mass loss in the first layer of the steel target during the transient entrance phase,with an extremely negligible loss in target mass during the quasi-steady penetration phase.The results of macro-analysis,micro-analysis and simulation show that the eroded target material migrated towards the periphery of the crater,causing an increase in the target's thickness,remained within the target,instead of flowing out of the crater.Therefore,the process of long rods penetrating the metal target is considered as a process of backward extrusion.By combining the backward extrusion theory with energy conservation,a penetration depth model for long rods penetrating a metal target,taking into account both the diameter of the crater and the friction coefficient between the rod and the target,has been established.Although the model is not yet perfect,it innovatively applies the principles of solid mechanics to the study of long rod penetration.Additionally,it takes into account the friction coefficient between the rod and the target during the penetration process.Therefore,this model provides a new research direction for future studies on long rod penetration.
文摘One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82174259 and 82304997)China Postdoctoral Followship Program of CPSF(Grant No.:GZC20233202)+4 种基金China Postdoctoral Science Foundation(Grant No.:2024M753698)the Key Research and Development Program of Hunan Province of China(Grant Nos.:2023SK2021 and 2022SK2015)the Natural Science Foundation of Hunan Province,China(Grant Nos.:2024JJ6632,2022JJ40853,and 2021JJ31117)the Hunan Traditional Chinese Medicine Scientific Research Program,China(Grant Nos.:B2024113,B2024114,and 2021032)the Fundamental Research Funds for the Central Universities of Central South University,China(Grant No.:1053320232786).
文摘Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.
基金supported by the National Natural Science Foundation of China,No.81571046(to KZ)Key Project of Educational Department of Liaoning Province,No.LJKZ0755(to KZ)+2 种基金Project of Department of Science&Technology of Liaoning Province,No.2023JH2/20200116(to KZ)Shenyang Young and Middleaged Innovative Talents Support Program,No.RC210240(to KZ)the 345 Talent Project of Shengjing Hospital of China Medical University(to LH)。
文摘Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were observed between amyloid-beta levels and the levels of TREM2(r=0.16,95%CI:0.04-0.28,P=0.009,I^(2)=74.7%),neprilysin(r=-0.47,95%CI:-0.80-0.14,P=0.005,I^(2)=76.1%),and P-glycoprotein(r=-0.31,95%CI:-0.51-0.11,P=0.002,I^(2)=0.0%)in patients with Alzheimer's disease.These findings suggest that triggering receptor expressed on myeloid cells 2 and cathepsin D could serve as potential diagnostic biomarkers for Alzheimer's disease,whereas triggering receptor expressed on myeloid cells 2,neprilysin,and P-glycoprotein may represent potential therapeutic targets.
基金supported by the CEA/DAM Laser Plasma Experiments Validation Project and the CEA/DAM Basic Technical and Scientific Studies Projectsupported by the National Sciences and Engineering Research Council of Canada(NSERC)(Grant Nos.RGPIN-2023-05459 and ALLRP 556340-20)+3 种基金the Digital Research Alliance of Canada(Job pve-323-ac)the Canada Foundation for Innovation(CFI)the Ministère de l’Économie,de l’Innovation et de l’Énergie(MEIE)from QuébecThis study was granted access to the HPC resources of IRENE under allocation Grant No.A0170512899 made by GENCI.We acknowledge the financial support of the IdEx University of Bordeaux/Grand Research Program“GPR LIGHT”and of the Graduate Program on Light Sciences and Technologies of the University of Bordeaux.
文摘Laser-driven ion acceleration,as produced by interaction of a high-intensity laser with a target,is a growing field of interest.One of the current challenges is to enhance the acceleration process,i.e.,to increase the produced ion energy and the ion number and to shape the energy distribution for future applications.In this paper,we investigate the effect of helical coil(HC)targets on the laser-matter interaction process using a 150 TW laser.We demonstrate that HC targets significantly enhance proton acceleration,improving energy bunching and beam focusing and increasing the cutoff energy.For the first time,we extend this analysis to carbon ions,revealing a marked reduction in the number of low-energy carbon ions and the potential for energy bunching and post-acceleration through an optimized HC design.Simulations using the particle-in-cell code SOPHIE confirm the experimental results,providing insights into the current propagation and ion synchronization mechanisms in HCs.Our findings suggest that HC targets can be optimized for multispecies ion acceleration.
基金Supported by the National Natural Science Foundation of China(No.81770920)Open Project of State Key Laboratory of Ophthalmology(No.303060202400383).
文摘AIM:To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma(POAG)based on a Mendelian randomization(MR)study.METHODS:Large-scale protein quantitative trait loci(pQTLs)data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study(GWAS)summary datasets were used in this study.Causal associations between plasma proteins and POAG were identified using summary-data-based MR(SMR)analysis and the heterogeneity in dependent instruments(HEIDI)test.Colocalization analysis was then conducted to assess the genetic associations between these two factors.Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects.Finally,protein-protein interactions(PPI)were studied,and the Drug-Gene Interaction Database(DGIDb)was used to identify associations between drugs and the identified proteins.RESULTS:Four proteins(SVEP1,TMEM190,ROBO1,and ENPP5)were identified as potential drug targets in this study.Phenome-wide MR analysis showed that SVEP1,ROBO1,and ENPP5 were not associated with adverse effects,while TMEM190 was linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.CONCLUSION:Four plasma proteins—SVEP1,TMEM190,ROBO1,and ENPP5—are identified as potential therapeutic targets for POAG through an MR approach.Phenome-wide MR analysis reveals that SVEP1,ROBO1,and ENPP5 are not associated with adverse effects,while TMEM190 is linked to nerve root and plexus disorders,as well as subarachnoid hemorrhage.Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1.These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.
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.
文摘It is difficult to improve both energy consumption and detection accuracy simultaneously,and even to obtain the trade-off between them,when detecting and tracking moving targets,especially for Underwater Wireless Sensor Networks(UWSNs).To this end,this paper investigates the relationship between the Degree of Target Change(DoTC)and the detection period,as well as the impact of individual nodes.A Hierarchical Detection and Tracking Approach(HDTA)is proposed.Firstly,the network detection period is determined according to DoTC,which reflects the variation of target motion.Secondly,during the network detection period,each detection node calculates its own node detection period based on the detection mutual information.Taking DoTC as pheromone,an ant colony algorithm is proposed to adaptively adjust the network detection period.The simulation results show that the proposed HDTA with the optimizations of network level and node level significantly improves the detection accuracy by 25%and the network energy consumption by 10%simultaneously,compared to the traditional adaptive period detection schemes.
文摘A measurement system for the scattering characteristics of warhead fragments based on high-speed imaging systems offers advantages such as simple deployment,flexible maneuverability,and high spatiotemporal resolution,enabling the acquisition of full-process data of the fragment scattering process.However,mismatches between camera frame rates and target velocities can lead to long motion blur tails of high-speed fragment targets,resulting in low signal-to-noise ratios and rendering conventional detection algorithms ineffective in dynamic strong interference testing environments.In this study,we propose a detection framework centered on dynamic strong interference disturbance signal separation and suppression.We introduce a mixture Gaussian model constrained under a joint spatialtemporal-transform domain Dirichlet process,combined with total variation regularization to achieve disturbance signal suppression.Experimental results demonstrate that the proposed disturbance suppression method can be integrated with certain conventional motion target detection tasks,enabling adaptation to real-world data to a certain extent.Moreover,we provide a specific implementation of this process,which achieves a detection rate close to 100%with an approximate 0%false alarm rate in multiple sets of real target field test data.This research effectively advances the development of the field of damage parameter testing.
