Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp...To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.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
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
Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpeno...Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpenoids(euphorwallside H and euphorwallside I,14 and 15),were isolated and characterized from Euphorbia wallichii(E.wallichii).The chemical structures of these compounds were elucidated through nuclear magnetic resonance(NMR),mass spectrometry(MS),and quantum chemical calculations.Compounds 9 and 11 demonstrated protective effects against H2O2-induced BV-2 microglial cell damage.Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR,GSTP1,and SHBG.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
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.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
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
Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism...Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism(ECD)/optical rotatory dispersion(ORD)methods,and X-ray crystallography.Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system,which is presumably biosynthesized via a[4+2]cycloaddition and an enzymatic cyclization.Chaeglobol A(1)exhibited inhibitory activity against B.dothidea by destroying cell membrane integrity and causing oxidative damage within the cells.展开更多
Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy densi...Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy density.However,the all-solid-state batteries with nickel-rich oxide cathodes suffer from performance degradation due to the reactions between the highly reactive surface oxygen of the cathode and the electrolyte,as well as the instability of the bulk oxygen structure in the cathode.Herein,we propose a synergistic modification design scheme to adjust the oxygen activity from surface to bulk.The LiBO_(2)coating inhibits the reactivity of surface lattice oxygen ions.Meanwhile,Zr doping in the bulk phase forms strong Zr-O covalent bonds that stabilize the bulk lattice oxygen structure.The synergistic effect of these modifications prevents the release of oxygen,thus avoiding the degradation of the cathode/SE interface.Additionally,the regulation of surface-to-bulk oxygen activity establishes a highly stable interface,thereby enhancing the lithium ion diffusion kinetics and mechanical stability of the cathode.Consequently,cathodes modified with this synergistic strategy exhibit outstanding performance in sulfide-based ASSLBs,including an ultra-long cycle life of 100,000 cycles,ultra-high rate capability at 45C,and 85% high active material content in the composite cathode.Additionally,ASSLB exhibits stable cycling under high loading conditions of 82.82 mg cm^(-2),achieving an areal capacity of 17.90 mA h cm^(-2).These encouraging results pave the way for practical applications of ASSLBs in fast charging,long cycle life,and high energy density in the future.展开更多
Water splitting hinges crucially on the availability of electrocatalysts for the oxygen evolution reaction.The surface reconstruction has been widely observed in perovskite catalysts,and the reconstruction degree has ...Water splitting hinges crucially on the availability of electrocatalysts for the oxygen evolution reaction.The surface reconstruction has been widely observed in perovskite catalysts,and the reconstruction degree has been often correlated with the activity enhancement.Here,a systematic study on the roles of Fe substitution in activation of perovskite LaNiO_(3)is reported.The substituting Fe content influences both current change tendency and surface reconstruction degree.LaNi_(0.9)Fe_(0.1)O_(3)is found exhibiting a volcano-peak intrinsic activity in both pristine and reconstructed among all substituted perovskites in the LaNi_(1-x)Fe_(x)O_(3)(x=0.00,0.10,0.25,0.50,0.75,1.00)series.The reconstructed LaNi_(0.9)Fe_(0.1)O_(3)shows a higher intrinsic activity than most reported NiFe-based catalysts.Besides,density functional theory calculations reveal that Fe substitution can lower the O 2p level,which thus stabilize lattice oxygen in LaNi0.9Fe0.1O3 and ensure its long-term stability.Furthermore,it is vital interesting that activity of the reconstructed catalysts relied more on the surface chemistry rather than the reconstruction degree.The effect of Fe on the degree of surface reconstruction of the perovskite is decoupled from that on its activity enhancement after surface reconstruction.This finding showcases the importance to customize the surface chemistry of reconstructed catalysts for water oxidation.展开更多
Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid ...Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.展开更多
Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More r...Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.展开更多
Eight sesquiterpenes were isolated from Ainsliaea glabra.Among them,a new guaianolide sesquiterpenoid,named ainsglaolide A(1),and seven known sesquiterpenoids 2~8 were identified.Compound 1 was a novel guaianolide ses...Eight sesquiterpenes were isolated from Ainsliaea glabra.Among them,a new guaianolide sesquiterpenoid,named ainsglaolide A(1),and seven known sesquiterpenoids 2~8 were identified.Compound 1 was a novel guaianolide sesquiterpenoid featuring a rare six-membered lactone ring formed between C-4 and C-15.The new compound structure was elucidated by HRESI-MS and NMR spectroscopy,as well as electrostatic circular dichroism(ECD)calculations were used to further confirm the absolute of 1.Anti-inflammatory activity tests were conducted on the separated compounds,indicating that compound 1 had significant inhibitory effect on NLRP3 inflammasome with an IC_(50) value of 1.86μmol/L.展开更多
Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interfe...Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interference devices(SQUID),MEG based on optically pump magnetometer(OPM)has the advantages of higher sensitivity,better spatial resolution and lower cost.However,most of the current studies are clinical studies,and there is a lack of animal studies on MEG based on OPM technology.Pain,a multifaceted sensory and emotional phenomenon,induces intricate alterations in brain activity,exhibiting notable sex differences.Despite clinical revelations of pain-related neuronal activity through MEG,specific properties remain elusive,and comprehensive laboratory studies on pain-associated brain activity alterations are lacking.The aim of this study was to investigate the effects of inflammatory pain(induced by Complete Freund’s Adjuvant(CFA))on brain activity in a rat model using the MEG technique,to analysis changes in brain activity during pain perception,and to explore sex differences in pain-related MEG signaling.Methods This study utilized adult male and female Sprague-Dawley rats.Inflammatory pain was induced via intraplantar injection of CFA(100μl,50%in saline)in the left hind paw,with control groups receiving saline.Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection.For MEG recording,anesthetized rats had an OPM positioned on their head within a magnetic shield,undergoing two 15-minute sessions:a 5-minute baseline followed by a 10-minute mechanical stimulation phase.Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms,generating spectrograms focused on the 4-30 Hz frequency range.Results MEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared,before and after saline/CFA injections.Mechanical stimulation elevated alpha activity in both male and female rats pre-and post-saline/CFA injections.Saline/CFA injections augmented average power in both sexes compared to pre-injection states.Remarkably,female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states.Furthermore,despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment,female rats displayed higher average power than males in the resting state after CFA injection.Conclusion These results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts.Our study exhibits sex differences in alpha activities following CFA injection,highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state.Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals.In addition,the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.展开更多
Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et a...Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.展开更多
A novel 3D metal-organic framework(MOF)[Pr_(2)(L)_(3)(H_(2)O)5·H_(2)O]n(Pr-1),(H_(2)L=4,4'-oxybis(benzoic acid))with a rare structure of broken layer net,was constructed under the condition of solvothermal sy...A novel 3D metal-organic framework(MOF)[Pr_(2)(L)_(3)(H_(2)O)5·H_(2)O]n(Pr-1),(H_(2)L=4,4'-oxybis(benzoic acid))with a rare structure of broken layer net,was constructed under the condition of solvothermal synthesis.The struc-ture and crystal net were analyzed and characterized.This rod net of Pr-1 is new to both RCSR and ToposPro data-bases,and is named as rn-12 as suggested.Due to the luminescent properties of H_(2)L and Pr(Ⅲ),the solid-state fluo-rescence property and sensing performance(solvents and metal ions)of Pr-1 were investigated.The sensing experi-ments indicated that Pr-1 could act as a fluorescence sensor to detect Cd^(2+)ions with good sensitivity.In addition,antibacterial activities show that Pr-1 exhibited stronger antibacterial activity against Escherichia coli(E.coli),Staphylococcus aureus(S.aureus),and Bacillus subtilis(B.subtilis)compared to synthetic materials.展开更多
The ongoing revolution in information technology is reshaping human life. In the realm of health behavior, wearable technology emerges as a leading digital solution,capturing physical behaviors (i.e., physical activit...The ongoing revolution in information technology is reshaping human life. In the realm of health behavior, wearable technology emerges as a leading digital solution,capturing physical behaviors (i.e., physical activity, sedentary habits, sleep patterns) within the 24-h cycle of daily life. Wearables are applied in research, clinical practice, and as lifestyle devices;most obvious, they promise to be a key element for increasing human physical activity, one of the biggest health challenges nowadays.展开更多
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
文摘To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
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.
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.82405016 and 82141216)the Project of Frontier Technology Platform for Research Projects of Liaoning Provincial Department of Education in 2024(No.LJ232410163056)+3 种基金"Select the best candidates to lead key research projects"of Fujian University of Traditional Chinese Medicine(Nos.XJB2022008 and XJB2023001)the Foundation of Fujian University of Traditional Chinese Medicine(Nos.X2023001-Talent and X2024002-Talent)the Young and Middle-aged Teacher Education Research Project in Fujian Province(No.JZ230023)the Central Government Guides Local Science and Technology Development Fund Projects(No.2023L3014).
文摘Thirteen novel diterpenoids,comprising seven tiglianes(walliglianes G−M,1−7),four rhamnofolanes(wallinofolanes A−D,8−11),and two daphnanes(wallaphnanes A and B,12 and 13),together with two known rhamnofolane diterpenoids(euphorwallside H and euphorwallside I,14 and 15),were isolated and characterized from Euphorbia wallichii(E.wallichii).The chemical structures of these compounds were elucidated through nuclear magnetic resonance(NMR),mass spectrometry(MS),and quantum chemical calculations.Compounds 9 and 11 demonstrated protective effects against H2O2-induced BV-2 microglial cell damage.Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR,GSTP1,and SHBG.
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,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
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 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funded by the S&T Program of Hebei(No.21323202D)the Natural Science Interdisciplinary Research Program of Hebei University(No.DXK201913)+4 种基金the Natural Sci-ence Foundation of Hebei Province of China(Nos.H2024201028,H2020201029)the Excellent Youth Research Innovation Team of Hebei University(No.QNTD202406)the Hebei University Research and Innovation Team(No.IT2023C1)the Innovation Capacity Improvement Plan of Hebei Province(No.20567605H)the National Training Program of Innovation and Entrepreneurship for Undergraduates(No.DC2024177)。
文摘Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism(ECD)/optical rotatory dispersion(ORD)methods,and X-ray crystallography.Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system,which is presumably biosynthesized via a[4+2]cycloaddition and an enzymatic cyclization.Chaeglobol A(1)exhibited inhibitory activity against B.dothidea by destroying cell membrane integrity and causing oxidative damage within the cells.
基金financially supported by the National Natural Science Foundation of China (52474338,22109084 and 52304338)the Hunan Provincial Key Research and Development Program (2024JK2093,2023GK2016)supported in part by the High Performance Computing Center of Central South University.
文摘Sulfide-based all-solid-state lithium batteries(ASSLBs) with nickel-rich oxide cathodes are emerging as primary contenders for the next generation rechargeable batteries,owing to their superior safety and energy density.However,the all-solid-state batteries with nickel-rich oxide cathodes suffer from performance degradation due to the reactions between the highly reactive surface oxygen of the cathode and the electrolyte,as well as the instability of the bulk oxygen structure in the cathode.Herein,we propose a synergistic modification design scheme to adjust the oxygen activity from surface to bulk.The LiBO_(2)coating inhibits the reactivity of surface lattice oxygen ions.Meanwhile,Zr doping in the bulk phase forms strong Zr-O covalent bonds that stabilize the bulk lattice oxygen structure.The synergistic effect of these modifications prevents the release of oxygen,thus avoiding the degradation of the cathode/SE interface.Additionally,the regulation of surface-to-bulk oxygen activity establishes a highly stable interface,thereby enhancing the lithium ion diffusion kinetics and mechanical stability of the cathode.Consequently,cathodes modified with this synergistic strategy exhibit outstanding performance in sulfide-based ASSLBs,including an ultra-long cycle life of 100,000 cycles,ultra-high rate capability at 45C,and 85% high active material content in the composite cathode.Additionally,ASSLB exhibits stable cycling under high loading conditions of 82.82 mg cm^(-2),achieving an areal capacity of 17.90 mA h cm^(-2).These encouraging results pave the way for practical applications of ASSLBs in fast charging,long cycle life,and high energy density in the future.
基金funded by the National Key R&D Program of China(2021YFA1501101)the National Natural Science Foundation of China(No.22471103,22425105,22201111,21931001,22221001,and 22271124)+5 种基金Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)the Special Fund Project of Guiding Scientific and Technological Innovation Development of Gansu Province(2019ZX-04)the 111 Project(B20027)as well as the National Natural Science Foundation of Gansu Province(22JR5RA470)the Fundamental Research Funds for the Central Universities(lzujbky-2023-eyt03)supported by the Agency for Science,Technology and Research(A*STAR)MTC Individual Research Grants(IRG)M22K2c0078.
文摘Water splitting hinges crucially on the availability of electrocatalysts for the oxygen evolution reaction.The surface reconstruction has been widely observed in perovskite catalysts,and the reconstruction degree has been often correlated with the activity enhancement.Here,a systematic study on the roles of Fe substitution in activation of perovskite LaNiO_(3)is reported.The substituting Fe content influences both current change tendency and surface reconstruction degree.LaNi_(0.9)Fe_(0.1)O_(3)is found exhibiting a volcano-peak intrinsic activity in both pristine and reconstructed among all substituted perovskites in the LaNi_(1-x)Fe_(x)O_(3)(x=0.00,0.10,0.25,0.50,0.75,1.00)series.The reconstructed LaNi_(0.9)Fe_(0.1)O_(3)shows a higher intrinsic activity than most reported NiFe-based catalysts.Besides,density functional theory calculations reveal that Fe substitution can lower the O 2p level,which thus stabilize lattice oxygen in LaNi0.9Fe0.1O3 and ensure its long-term stability.Furthermore,it is vital interesting that activity of the reconstructed catalysts relied more on the surface chemistry rather than the reconstruction degree.The effect of Fe on the degree of surface reconstruction of the perovskite is decoupled from that on its activity enhancement after surface reconstruction.This finding showcases the importance to customize the surface chemistry of reconstructed catalysts for water oxidation.
基金funded by the National Key Research and Development Program of China(No.2022YFC2804101)the Guangdong Provincial Key R&D Program(No.2023B1111050011)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)the Guangzhou Basic and Applied Basic Research Foundation(No.202201010305)the High-Level Talents Special Program of Zhejiang(No.2022R52036)。
文摘Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.
基金supported by the National Natural Science Foundation of China,Nos.82404892(to QY),82061160374(to ZZ)the Science and Technology Development Fund,Macao Special Administrative Region,China,Nos.0023/2020/AFJ,0035/2020/AGJ+2 种基金the University of Macao Research Grant,Nos.MYRG2022-00248-ICMS,MYRG-CRG2022-00010-ICMS(to MPMH)the Natural Science Foundation of Guangdong Province,No.2024A1515012818(to ZZ)the Fundamental Research Funds for the Central Universities,No.21623114(to ZZ).
文摘Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.
文摘Eight sesquiterpenes were isolated from Ainsliaea glabra.Among them,a new guaianolide sesquiterpenoid,named ainsglaolide A(1),and seven known sesquiterpenoids 2~8 were identified.Compound 1 was a novel guaianolide sesquiterpenoid featuring a rare six-membered lactone ring formed between C-4 and C-15.The new compound structure was elucidated by HRESI-MS and NMR spectroscopy,as well as electrostatic circular dichroism(ECD)calculations were used to further confirm the absolute of 1.Anti-inflammatory activity tests were conducted on the separated compounds,indicating that compound 1 had significant inhibitory effect on NLRP3 inflammasome with an IC_(50) value of 1.86μmol/L.
文摘Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interference devices(SQUID),MEG based on optically pump magnetometer(OPM)has the advantages of higher sensitivity,better spatial resolution and lower cost.However,most of the current studies are clinical studies,and there is a lack of animal studies on MEG based on OPM technology.Pain,a multifaceted sensory and emotional phenomenon,induces intricate alterations in brain activity,exhibiting notable sex differences.Despite clinical revelations of pain-related neuronal activity through MEG,specific properties remain elusive,and comprehensive laboratory studies on pain-associated brain activity alterations are lacking.The aim of this study was to investigate the effects of inflammatory pain(induced by Complete Freund’s Adjuvant(CFA))on brain activity in a rat model using the MEG technique,to analysis changes in brain activity during pain perception,and to explore sex differences in pain-related MEG signaling.Methods This study utilized adult male and female Sprague-Dawley rats.Inflammatory pain was induced via intraplantar injection of CFA(100μl,50%in saline)in the left hind paw,with control groups receiving saline.Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection.For MEG recording,anesthetized rats had an OPM positioned on their head within a magnetic shield,undergoing two 15-minute sessions:a 5-minute baseline followed by a 10-minute mechanical stimulation phase.Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms,generating spectrograms focused on the 4-30 Hz frequency range.Results MEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared,before and after saline/CFA injections.Mechanical stimulation elevated alpha activity in both male and female rats pre-and post-saline/CFA injections.Saline/CFA injections augmented average power in both sexes compared to pre-injection states.Remarkably,female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states.Furthermore,despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment,female rats displayed higher average power than males in the resting state after CFA injection.Conclusion These results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts.Our study exhibits sex differences in alpha activities following CFA injection,highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state.Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals.In addition,the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
文摘Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.
文摘A novel 3D metal-organic framework(MOF)[Pr_(2)(L)_(3)(H_(2)O)5·H_(2)O]n(Pr-1),(H_(2)L=4,4'-oxybis(benzoic acid))with a rare structure of broken layer net,was constructed under the condition of solvothermal synthesis.The struc-ture and crystal net were analyzed and characterized.This rod net of Pr-1 is new to both RCSR and ToposPro data-bases,and is named as rn-12 as suggested.Due to the luminescent properties of H_(2)L and Pr(Ⅲ),the solid-state fluo-rescence property and sensing performance(solvents and metal ions)of Pr-1 were investigated.The sensing experi-ments indicated that Pr-1 could act as a fluorescence sensor to detect Cd^(2+)ions with good sensitivity.In addition,antibacterial activities show that Pr-1 exhibited stronger antibacterial activity against Escherichia coli(E.coli),Staphylococcus aureus(S.aureus),and Bacillus subtilis(B.subtilis)compared to synthetic materials.
基金funded in part by the German Research Foundation(Grant reference:496846758).
文摘The ongoing revolution in information technology is reshaping human life. In the realm of health behavior, wearable technology emerges as a leading digital solution,capturing physical behaviors (i.e., physical activity, sedentary habits, sleep patterns) within the 24-h cycle of daily life. Wearables are applied in research, clinical practice, and as lifestyle devices;most obvious, they promise to be a key element for increasing human physical activity, one of the biggest health challenges nowadays.
