Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures o...Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures of cardiac myocytes from 1-to 3-day-old Wistar rats were prepared,and myocytes were ex-posed to lipopolysaccharide(LPS)and varying concentrations of PPARαor PPARγactivator(fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα,PPARα,and PPARγexpression in cultured cardiac myocytes.Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB(NF-κB)binding site to cardiac myocytes was performed.Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner.However,no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone.Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter(-721/+17)after being stimulated with LPS and fenofibrate or pioglitazone,whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site(-182/+17).Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression.Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation.The mechanism may partly be involved in suppression of the NF-κB pathway.展开更多
Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its com...Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.展开更多
A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-...A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.展开更多
The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a ...The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.展开更多
Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the pos...Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.展开更多
The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were d...The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.展开更多
Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding whee...Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding wheels were then prepared from Ni-coated diamond composite powders with different activators. The microstructural characterizations of this composite powders were finally conducted by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction, and the mechanical and tribological properties of as-prepared diamond grinding wheels were also measured. There are changes in microstructures and properties of the composite powders with activators. The activator concentration also has an influence on the morphologies and phase structures of the Ni coating on diamond particles.The composite powders with more compact coating of nickel can be prepared by adding 1 g dm^（-3） or more AgNO_3 as an activator to electrodeposit nickel on diamond. The mechanical and tribological properties of diamond grinding wheels were significantly improved when the coating phase structure of Ni crystal grew with（111） plane orientation on the surface of diamond particles. The wheels made from nickel coated diamond composite powders possessed the advantages of easy preparation and outstanding tribological properties. Therefore, Ni coated diamond composite powders exhibit a great potential to be extensively applied in diamond cutting and grinding tools.展开更多
Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial...Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial cells (EC-CM),the PA activities of the latter decreased significantly. Cocultivation of EC with SMC alsoresulted in a significant decrease (70.7%) of PA activities produced by EC. Sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of SMC-CMfollowed by reverse fibrin autography demonstrated that the PA inhibitor had a molecularweight of 49000-62000. In this study we also investigated the effect of a Chinese herbalmedicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity of SMC. The re-sults showed that RSM significantly decreased the inhibitory activity of SMC against thePA secreted by EC.展开更多
Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators agains...Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators against Src homology region 2 domain-containing phosphatase-1(SHP-1)to block STAT3 pathway represents a promising strategy for DLBCL therapy.Here we reported a new class of thieno[2,3-b]quinolineprocaine hybrid molecules as SHP-1 allosteric activators.The representative hybrid compound 3b displayed SHP-1 activating effect with EC50 of 5.48±0.28μmol/L.Further investigations confirmed that 3b allosterically interacted with SHP-1,switched it from close to open conformation,blocked SHP-1/p-STAT3 pathway,induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro,and delayed tumor growth in the xenograft model of SU-DHL-2.Overall,this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors,and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway.展开更多
Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted...Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted and a series of benzotriazole derivatives were designed and synthesized.The bioassay showed that benzotriazole had high activity against a broad spectrum of diseases including fungi and oomycetes in vivo,but no activity in vitro.And the introduction of proper groups at the1＇-position and 5＇-position was beneficial to the activity.So,they had the potential to be exploited as novel plant activators.展开更多
Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistan...Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.展开更多
The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat ...The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat proteins(NLRs)represent the largest family of intracellular immune receptors,responsible for the detection of rapidly evolving pathogen-secreted effec-tors and the initiation of effector-triggered immunity(ETI).展开更多
Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible p...Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter.Previous reconstruction of gene circuits highly improved transcriptional activity,but excessive expression of chimeric transactivator damaged cell growth on methanol.Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regula-tory networks.The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism,especially the alcohol oxidase 1(AOX1),but without remarkable changes in expression of transcriptional factors.Meanwhile,the synthesis of peroxisomes also varied with chimeric transactivator expression.In addition,the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism.The gene expression patterns caused by different expression levels of chimeric trans-activators have also been clarified.This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling.It revealed the importance of balancing transcription factor expression for the host improvement.展开更多
Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observe...Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking rec...BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking recovery.OBJECTIVE:To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms.METHODS:Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group(n=16)and the control group(n=16).Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily,5 days a week.The experimental group used the personal assistant machine during training.Three-dimensional gait analysis(using the Cortex motion capture system),Brunnstrom staging,Fugl-Meyer Assessment for lower limb motor function,Fugl-Meyer balance function,and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention.RESULTS AND CONCLUSION:After the 4-week intervention,all outcome measures showed significant changes in each group.The experimental group had a small but significant increase in the modified Ashworth Scale score(P<0.05,d=|0.15|),while the control group had a large significant increase(P<0.05,d=|1.48|).The experimental group demonstrated greater improvements in walking speed(16.5 to 38.44 cm/s,P<0.05,d=|4.01|),step frequency(46.44 to 64.94 steps/min,P<0.05,d=|2.32|),stride length(15.50 to 29.81 cm,P<0.05,d=|3.44|),and peak hip and knee flexion(d=|1.82|to|2.17|).After treatment,the experimental group showed significantly greater improvements than the control group in walking speed(38.44 vs.26.63 cm/s,P<0.05,d=|2.75|),stride length,peak hip and knee flexion(d=|1.31|to|1.45|),step frequency(64.94 vs.59.38 steps/min,P<0.05,d=|0.85|),and a reduced support phase(bilateral:24.31%vs.28.38%,P<0.05,d=|0.88|;non-paretic:66.19%vs.70.13%,P<0.05,d=|0.94|).For early hemiplegia,personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern,prevents muscle spasms,and improves motor function.展开更多
Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-relate...Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
With the growing advancement of wireless communication technologies,WiFi-based human sensing has gained increasing attention as a non-intrusive and device-free solution.Among the available signal types,Channel State I...With the growing advancement of wireless communication technologies,WiFi-based human sensing has gained increasing attention as a non-intrusive and device-free solution.Among the available signal types,Channel State Information(CSI)offers fine-grained temporal,frequency,and spatial insights into multipath propagation,making it a crucial data source for human-centric sensing.Recently,the integration of deep learning has significantly improved the robustness and automation of feature extraction from CSI in complex environments.This paper provides a comprehensive review of deep learning-enhanced human sensing based on CSI.We first outline mainstream CSI acquisition tools and their hardware specifications,then provide a detailed discussion of preprocessing methods such as denoising,time–frequency transformation,data segmentation,and augmentation.Subsequently,we categorize deep learning approaches according to sensing tasks—namely detection,localization,and recognition—and highlight representative models across application scenarios.Finally,we examine key challenges including domain generalization,multi-user interference,and limited data availability,and we propose future research directions involving lightweight model deployment,multimodal data fusion,and semantic-level sensing.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
基金Supported by the National Nature Science Foundation of China(30270551)Military"10.5"Foundation(02M012).
文摘Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα)and PPARγactivators on tumor necrosis factor-α(TNFα)expression in neonatal rat cardiac myocytes.Methods Primary cultures of cardiac myocytes from 1-to 3-day-old Wistar rats were prepared,and myocytes were ex-posed to lipopolysaccharide(LPS)and varying concentrations of PPARαor PPARγactivator(fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα,PPARα,and PPARγexpression in cultured cardiac myocytes.Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB(NF-κB)binding site to cardiac myocytes was performed.Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner.However,no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone.Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter(-721/+17)after being stimulated with LPS and fenofibrate or pioglitazone,whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site(-182/+17).Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression.Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation.The mechanism may partly be involved in suppression of the NF-κB pathway.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073814,81973291,82122066,and 82003909)the Rising-Star Program of Shanghai Science and Technology Committee(Grant No.:19QA1411500).
文摘Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell activators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside IV,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory components of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
基金financially supported by the National Nature Science Foundation of China(No.30572256)
文摘A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.
基金the Start- up Fund for Returned Overseas Scholars from Northeast Normal U niversity,National ScienceFund for Distinguished Young Scholars(No.30 32 5 0 11) ,Distinguished Young Scholars Fund of Jilin Province(No.2 0 0 30 112 ) ,Excellent Young Teachers Pr
文摘The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.
文摘Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.
基金financially supported by the National Basic Research Program of China (973 Program, No. 2010CB126100)the National High Technology Research and Development Program of China (863 Program, No. 2011AA10A207)+1 种基金the China 111 Project (No. B07023)the Fundamental Research Funds for the Central Universities.
文摘The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.
基金funded by the National Natural Science Foundation of China (Nos. 21476066 and 51271074)
文摘Nickel coated diamond composite powders were fabricated via a newly developed direct electrodeposition technique. The effects of activators on the coating of diamond were firstly investigated and diamond grinding wheels were then prepared from Ni-coated diamond composite powders with different activators. The microstructural characterizations of this composite powders were finally conducted by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction, and the mechanical and tribological properties of as-prepared diamond grinding wheels were also measured. There are changes in microstructures and properties of the composite powders with activators. The activator concentration also has an influence on the morphologies and phase structures of the Ni coating on diamond particles.The composite powders with more compact coating of nickel can be prepared by adding 1 g dm^（-3） or more AgNO_3 as an activator to electrodeposit nickel on diamond. The mechanical and tribological properties of diamond grinding wheels were significantly improved when the coating phase structure of Ni crystal grew with（111） plane orientation on the surface of diamond particles. The wheels made from nickel coated diamond composite powders possessed the advantages of easy preparation and outstanding tribological properties. Therefore, Ni coated diamond composite powders exhibit a great potential to be extensively applied in diamond cutting and grinding tools.
文摘Cultured porcine endothelial cells (EC) produce and secrete plasminogenactivators (PA). If the serum free media incubated by vascular smooth muscle cells(SMC-CM) were mixed with the same media incubated by endothelial cells (EC-CM),the PA activities of the latter decreased significantly. Cocultivation of EC with SMC alsoresulted in a significant decrease (70.7%) of PA activities produced by EC. Sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of SMC-CMfollowed by reverse fibrin autography demonstrated that the PA inhibitor had a molecularweight of 49000-62000. In this study we also investigated the effect of a Chinese herbalmedicine-Radix Salviae Miltiorrhizae (RSM) on the inhibitory activity of SMC. The re-sults showed that RSM significantly decreased the inhibitory activity of SMC against thePA secreted by EC.
基金supported by National Natural Science Foundation of China(Nos.81773779,21772068 and 22277043)National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(No.2018ZX09711002-007-1)+1 种基金Natural Science Foundation of Jiangsu Province(No.BK20190608)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX22_2330).
文摘Small molecule activators could equally provide powerful tools as inhibitors do for interrogating cellular signal transduction.However,targeted protein activation is chemically challenging.Developing activators against Src homology region 2 domain-containing phosphatase-1(SHP-1)to block STAT3 pathway represents a promising strategy for DLBCL therapy.Here we reported a new class of thieno[2,3-b]quinolineprocaine hybrid molecules as SHP-1 allosteric activators.The representative hybrid compound 3b displayed SHP-1 activating effect with EC50 of 5.48±0.28μmol/L.Further investigations confirmed that 3b allosterically interacted with SHP-1,switched it from close to open conformation,blocked SHP-1/p-STAT3 pathway,induced apoptosis and inhibited ABC-DLBCL cell proliferation in vitro,and delayed tumor growth in the xenograft model of SU-DHL-2.Overall,this work offered a novel paradigm to develop SHP-1 allosteric activators through chemical space evolution of PTPs inhibitors,and firstly validated the therapeutic strategy that directly activating SHP-1 alone could be a potential therapy against ABC-DLBCL via blocking STAT3 pathway.
基金financially supported by the National Basic Research Program of China(973 Program,No.2010CB126100)the National High Technology Research and Development Program of China(863 Program,No.2011AA10A207)+1 种基金the Shanghai Leading Academic Discipline Project(B507)the Fundamental Research Funds for the Central Universities
文摘Started from salicylic acid（SA） and related commercialized plant activators,based on molecular threedimensional shape and pharmacophore similarity comparison（SHAFTS）,a new lead compound benzotriazole was predicted and a series of benzotriazole derivatives were designed and synthesized.The bioassay showed that benzotriazole had high activity against a broad spectrum of diseases including fungi and oomycetes in vivo,but no activity in vitro.And the introduction of proper groups at the1＇-position and 5＇-position was beneficial to the activity.So,they had the potential to be exploited as novel plant activators.
基金supported by Department of Science and Technology and Biotechnology,GoWB,India(Sanction No.:140(Sanc.)-BT/P/Budget/RD-75/2017 dated 16.11.2018)to U.CDST-FIST,GoI for providing infrastructure support to Department of Zoology,University of Calcutta+2 种基金CSIR,GoI,for funding their fellowship(File No.09/028(1066)/2018-EMRI and 09/028(1138)/2019-EMR-I,respectively)supported by a grant from the Natural Sciences and Engineering Research Council of Canadasupported by a Queen Elizabeth Ⅱ Diamond Jubilee Scholarship and an FRQ-NT scholarship.
文摘Persistence of drug-resistant breast cancer stem cells(brCSCs)after a chemotherapeutic regime correlates with disease recurrence and elevated mortality.Therefore,deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies.The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance,and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs.However,pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces.Therefore,transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs.Incidentally,transcriptional co-activators YAP/TAZ were found to be upregulated in CD44^(+)/CD24^(-)/ALDH^(+)cells isolated from patient breast tumors and CSC-enriched mammospheres.Interestingly,it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres,leading to significantly reduced sphere forming efficiency and cell viability.YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker,DRP1.Furthermore,YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS,consequently inducing apoptosis in mammospheres.In order to enhance clinical relevance of the study,an FDA-approved drug verteporfin(VP),was used for pharmacological inhibition of YAP/TAZ.Surprisingly,VP administration was found to reduce tumor-initiating capacity of the mammospheres,concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population.Therefore,VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs,offering a potent strategy for managing tumor recurrence effectively.
基金supported by the Outstanding Young Teacher of the“QingLan Project”of Jiangsu Province.
文摘The long-term evolutionary arms race between plants and path-ogens has shaped the abundant immune receptor repertoires in plants to counteract pathogens(Jones et al.,2024).Plant nucleotide-binding leucine-rich repeat proteins(NLRs)represent the largest family of intracellular immune receptors,responsible for the detection of rapidly evolving pathogen-secreted effec-tors and the initiation of effector-triggered immunity(ETI).
基金supported by National Key Research and Development Program of China(2022YFC2805102)Young Scientist Fund of National Natural Science Foundation of China(32201206)China Postdoctoral Science Foundation(2022M711146)。
文摘Methanol is a promising substrate for sustainable biomanufacturing,and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter.Previous reconstruction of gene circuits highly improved transcriptional activity,but excessive expression of chimeric transactivator damaged cell growth on methanol.Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regula-tory networks.The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism,especially the alcohol oxidase 1(AOX1),but without remarkable changes in expression of transcriptional factors.Meanwhile,the synthesis of peroxisomes also varied with chimeric transactivator expression.In addition,the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism.The gene expression patterns caused by different expression levels of chimeric trans-activators have also been clarified.This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling.It revealed the importance of balancing transcription factor expression for the host improvement.
基金funding provided by Royal Institute of Technology.This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation(72110).
文摘Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
文摘BACKGROUND:Hemiplegia,a prevalent stroke-related condition,is often studied for motor dysfunction;however,spasticity remains under-researched.Abnormal muscle tone significantly hinders hemiplegic patients’walking recovery.OBJECTIVE:To determine whether early suspension-protected training with a personal assistant machine for stroke patients enhances walking ability and prevents muscle spasms.METHODS:Thirty-two early-stage stroke patients from Shenzhen University General Hospital and the China Rehabilitation Research Center were randomly assigned to the experimental group(n=16)and the control group(n=16).Both groups underwent 4 weeks of gait training under the suspension protection system for 30 minutes daily,5 days a week.The experimental group used the personal assistant machine during training.Three-dimensional gait analysis(using the Cortex motion capture system),Brunnstrom staging,Fugl-Meyer Assessment for lower limb motor function,Fugl-Meyer balance function,and the modified Ashworth Scale were evaluated within 1 week before the intervention and after 4 weeks of intervention.RESULTS AND CONCLUSION:After the 4-week intervention,all outcome measures showed significant changes in each group.The experimental group had a small but significant increase in the modified Ashworth Scale score(P<0.05,d=|0.15|),while the control group had a large significant increase(P<0.05,d=|1.48|).The experimental group demonstrated greater improvements in walking speed(16.5 to 38.44 cm/s,P<0.05,d=|4.01|),step frequency(46.44 to 64.94 steps/min,P<0.05,d=|2.32|),stride length(15.50 to 29.81 cm,P<0.05,d=|3.44|),and peak hip and knee flexion(d=|1.82|to|2.17|).After treatment,the experimental group showed significantly greater improvements than the control group in walking speed(38.44 vs.26.63 cm/s,P<0.05,d=|2.75|),stride length,peak hip and knee flexion(d=|1.31|to|1.45|),step frequency(64.94 vs.59.38 steps/min,P<0.05,d=|0.85|),and a reduced support phase(bilateral:24.31%vs.28.38%,P<0.05,d=|0.88|;non-paretic:66.19%vs.70.13%,P<0.05,d=|0.94|).For early hemiplegia,personal assistant machine-assisted gait training under the suspension protection system helps establish a correct gait pattern,prevents muscle spasms,and improves motor function.
基金supported by the Jilin Science and Technology Development Talent Special Project,Nos.20240601086RC,23JQ08(all to ZH)YDZJ202502CXJD077+1 种基金JLARS-2025-0802-09YDZJ202501ZYTS706.
文摘Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金supported by National Natural Science Foundation of China(NSFC)under grant U23A20310.
文摘With the growing advancement of wireless communication technologies,WiFi-based human sensing has gained increasing attention as a non-intrusive and device-free solution.Among the available signal types,Channel State Information(CSI)offers fine-grained temporal,frequency,and spatial insights into multipath propagation,making it a crucial data source for human-centric sensing.Recently,the integration of deep learning has significantly improved the robustness and automation of feature extraction from CSI in complex environments.This paper provides a comprehensive review of deep learning-enhanced human sensing based on CSI.We first outline mainstream CSI acquisition tools and their hardware specifications,then provide a detailed discussion of preprocessing methods such as denoising,time–frequency transformation,data segmentation,and augmentation.Subsequently,we categorize deep learning approaches according to sensing tasks—namely detection,localization,and recognition—and highlight representative models across application scenarios.Finally,we examine key challenges including domain generalization,multi-user interference,and limited data availability,and we propose future research directions involving lightweight model deployment,multimodal data fusion,and semantic-level sensing.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
