[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were scre...[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.展开更多
[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were...[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.展开更多
[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was dow...[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and all targets of GAA were predicted by converting 3D model molecules into SMILES online tool and Swiss target prediction.Genecards database and DisGeNET database were used to find the targets related to MI,and then Venny 2.1.0 was used to generate the corresponding Wayne diagram,and then Cytoscape 3.9.1 software was used to construct the protein-protein interaction(PPI)network.With the help of DAVID database and Microbiology,the selected core targets were enriched and analyzed by gene ontology(GO),biological process(BP),and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the molecular docking between GAA and core targets was verified by AutoDock and Pymol software.[Results]A total of 1883 MI targets were screened,and in the protein-protein interaction network,AKT1,PTGS2,PPARG,ESR1,GSK3B were the proteins with higher values.Gene ontology and KEEG enrichment analysis showed that the biological processes involved mainly included inflammatory response,negative regulation of gene expression,and response to exogenous stimuli.Signaling pathways mainly include IL-17 signaling pathway,HIF-1 signaling pathway,and so on.The results of molecular docking showed that the binding energy of GAA and core protein was less than-5 Kcal/mol in four groups.These indicated that GAA with good binding had a certain therapeutic effect on myocardial ischemia.[Conclusions]Based on the systematic network pharmacology method,this study predicts the basic pharmacological effects and potential mechanisms of GAA in the treatment of MI,and reveals that GAA may treat MI through multiple targets and signaling pathways.It is expected to provide a basis for further study of its pharmacological mechanisms.展开更多
CO impurity-induced catalyst deactivation has long been one of the biggest challenges in proton-exchange membrane fuel cells,with the poisoning phenomenon mainly attributed to the overly strong adsorption on the catal...CO impurity-induced catalyst deactivation has long been one of the biggest challenges in proton-exchange membrane fuel cells,with the poisoning phenomenon mainly attributed to the overly strong adsorption on the catalytic site.Here,we present a mechanistic study that overturns this understanding by using Rh-based single-atom catalysis centers as model catalysts.We precisely modulated the chelation structure of the Rh catalyst by coordinating Rh with C or N atoms,and probed the reaction mechanism by surface-enhanced Raman spectroscopy.Direct spectroscopic evidence for intermediates indicates that the reactivity of adsorbed OH^(*),rather than the adsorption strength of CO^(*),dictates the CO electrocatalytic oxidation behavior.The RhN_(4)sites,which adsorb the OH^(*)intermediate more weakly than RhC4 sites,showed prominent CO oxidation activity that not only far exceeded the traditional Pt/C but also the RhC4 sites with similar CO adsorption strength.From this study,it is clear that a paradigm shift in future research should be considered to rationally design high-performance CO electro-oxidation reaction catalysts by sufficiently considering the water-related reaction intermediate during catalysis.展开更多
[Objectives]This study was conducted to clarify the action mechanism of Pseudostellariae Radix in regulating angiogenesis by using network pharmacology and a dual-screening system,and to provide a basis for its clinic...[Objectives]This study was conducted to clarify the action mechanism of Pseudostellariae Radix in regulating angiogenesis by using network pharmacology and a dual-screening system,and to provide a basis for its clinical treatment of cardiovascular diseases.[Methods]The TCMSP database was used for preliminary screening to obtain the active compounds of Pseudostellariae Radix and the protein targets of its action.GeneCards and OMIM databases were used to search for targets related to angiogenesis.Cytoscape 3.9.1 was used to construct a drug-target network and protein interaction network of Pseudostellariae Radix in angiogenesis.The GO enrichment analysis and KEGG pathway analysis of the targets of Pseudostellariae Radix in angiogenesis were carried out on Metascape platform.The effects of the screened active compounds were verified using a dual-screening system.[Results]Six active components of Pseudostellariae Radix,luteolin,acetin,beta-sitosterol,linarin,schottenol and 1-monolinolein,were screened by TCMSP database;and the six active components were predicted with 78 common target proteins related to angiogenesis,of which 19 were core targets.Pseudostellariae Radix mainly intervened in angiogenesis through domain specific binding,ubiquitin-like protein ligase binding,kinase binding and other molecular functions to regulate biological processes such as membrane microdomain,plasma membrane raft and caveola.The results of KEGG enrichment indicated that pathways in cancer,lipid and atherosclerosis,hepatitis B,apoptosis,toxoplasmosis and other key pathways might be the mechanism for the intervention of angiogenesis.The results of the dual-screening system showed that luteolin,acacetin,beta-sitosterol and linarin protected HUVECs and promoted zebrafish angiogenesis.[Conclusions]This study preliminarily demonstrated that luteolin,acacetin,beta-sitosterol and linarin could intervene in angiogenesis through multiple targets and multiple pathways,providing ideas and a scientific basis for the treatment of cardiovascular diseases.展开更多
[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and...[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.展开更多
This study aimed to determine the effectiveness of comprehensive rehabilitation for patients with aneurysmal subarachnoid hemorrhage (aSAH) and to explore the factors influencing the prognosis of rehabilitation. This ...This study aimed to determine the effectiveness of comprehensive rehabilitation for patients with aneurysmal subarachnoid hemorrhage (aSAH) and to explore the factors influencing the prognosis of rehabilitation. This was a retrospective study. Twenty-five patients with aSAH were treated with physical therapy, occupational therapy, speech therapy, cognitive therapy, music therapy, Chinese acupuncture, hyperbaric oxygen, and transcranial magnetic stimulation. The general data of all patients were collected, and the functional scores at admission were compared with those at discharge. The Mini Mental State Examination, Fugl-Meyer Assessment Scale (FMAS) for motor and balance assessment, Holden Functional Ambulation Classification (FAC), modified Rankin Scale, National Institute of Health Stroke Scale, Modified Barthel Index for activities of daily living (ADL), and Glasgow Outcome Scale were significantly improved among 25 patients with aSAH after 1 month of comprehensive rehabilitation training. Hydrocephalus was an independent factor of the ability to perform ADLs (odds ratio, 0.29;95% confidence interval, 2.03. 3.15;p = 0.000). The improvement of ADLs in aSAH patients was not related to sex, surgical method, aneurysm location, age, or smoking status. Comprehensive and professional rehabilitation is effective for the cognition, movement, walking, ADLs, and functional prognosis of patients with aSAH, while early hydrocephalus may be a risk factor for poor ADLs.展开更多
Cobalt carbide(Co2C)was considered as potential catalysts available for large-scale industrialization of transforming syngas(H2 and CO)to clean fuels.Herein,we successfully synthesized Co-based catalysts with MnO supp...Cobalt carbide(Co2C)was considered as potential catalysts available for large-scale industrialization of transforming syngas(H2 and CO)to clean fuels.Herein,we successfully synthesized Co-based catalysts with MnO supported,to comprehend the effects of Co2C for Fischer–Tropsch synthesis(FTS)under ambient conditions.The huge variety of product selectivity which was contained by different active sites(Co and Co2C)has been found.Furthermore,density functional theory(DFT)shows that Co2C is efficacious of CO adsorption,whereas is weaker for H adsorption than Co.Combining the advantages of Co and Co2C,the catalyst herein can not only obtain more C5+products but also suppress methane selectivity.It can be a commendable guide for the design of industrial application products in FTS.展开更多
Understanding of the oxygen reduction reaction(ORR)mechanism for single atom catalysts is pivotal for the rational design of non-precious metal cathode materials and the commercialization of fuel cells.Herein,a series...Understanding of the oxygen reduction reaction(ORR)mechanism for single atom catalysts is pivotal for the rational design of non-precious metal cathode materials and the commercialization of fuel cells.Herein,a series of non-precious metal electrocatalysts based on nitrogen-doped bimetallic(Fe and Co)carbide were modeled by density functional theory calculations to predict the corresponding reaction pathways.The study elucidated prior oxygen adsorption on the Fe atom in the dual site and the modifier role of Co atoms to tune the electronic structures of Fe.The reaction activity was highly correlated with the bimetallic center and the coordination environment of the adjacent nitrogen.Interestingly,the preadsorption of*OH resulted in the apparent change of metal atoms'electronic states with the d-band center shifting toward the Fermi level,thereby boosting reaction activity.The result should help promote the fundamental understanding of active sites in ORR catalysts and provide an effective approach to the design of highly efficient ORR catalysts on an atomic scale.展开更多
Constructing heterostructure is an important strategy to design efficient electrocatalysts. The synergetic interaction between dissimilar materials has been considered as the origin of the activity enhancement,however...Constructing heterostructure is an important strategy to design efficient electrocatalysts. The synergetic interaction between dissimilar materials has been considered as the origin of the activity enhancement,however, the interfacial interaction is challenging to probe, thus, the underlying mechanism remains obscure. Here, we reported a heterostructured α-MoC/β-Mo2 C electrocatalyst for hydrogen evolution in alkaline media, which shows a significant electrocatalytic activity improvement as compared to the single component. Based on extensive characterizations including high-resolution transmission electron microscopy and X-ray absorption fine structure(XAFS) spectroscopy, together with density functional theory, we unraveled the synergetic interaction between α-MoC and β-Mo2 C, implying that α-Mo C sites are beneficial for water dissociation and hydrogen prefers to release on β-Mo2 C sites.展开更多
Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases.In this study,a new type of hydrogen peroxide(H_(2)...Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases.In this study,a new type of hydrogen peroxide(H_(2)O_(2)T-activated photoacoustic nanoprobe[Mn-AH nanoscale coordination polymer nanodots(NCPs)]was successfully synthesized by a simple one-step method in water phase containing 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),horse radish peroxidase(HRP),and manganese ion(Mn^(2+).After modification by polyethylene glycol(PEG),Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H_(2)O_(2)-responsive chromogenic assay with great speci¯city and sensitivity.In the presence of H_(2)O_(2),colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared(NIR)absorbance,enabling photoacoustic detection of endogenous H_(2)O_(2).Using H_(2)O_(2)-activated Mn-AH NCPs,we have successfully performed PA imaging and H_(2)O_(2)detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder tumor.Due to the inherent Mn element existence inside the Mn-AH,this nanoprobe also serves as a good T1-weighted magnetic resonance imaging(MRI)contrast agent simultaneously.Lastly,after accomplishing its imaging functions,the Mn-AH NCPs could be cleared out from the body without any long-term toxicity,providing a new opportunity for cancer diagnosis and treatment.展开更多
Sewer networks play a vital role in sewage collection and transportation,and they are being rapidly expanded.However,the microbial processes occurring within these networks have emerged as significant contributors to ...Sewer networks play a vital role in sewage collection and transportation,and they are being rapidly expanded.However,the microbial processes occurring within these networks have emerged as significant contributors to greenhouse gas(GHG)emissions.Compared to that from other sectors,our understanding of the magnitude of GHG emissions from sewer networks is currently limited.In this study,we conducted a GHG emission assessment in an independent sewer network located in Beijing,China.The findings revealed annual emissions of 62.3 kg CH_(4) and 0.753 kg N20.CH_(4) emerged as the primary GHG emitted from sewers,accounting for 87.4%of the total GHG emissions.Interestingly,compared with main pipes,branch pipes were responsible for a larger share of GHG emissions,contributing to 76.7%of the total.A GHG emission factor of 0.26 kg CO_(2)-eq/(m:yr)was established to quantify sewer GHG emissions.By examining the isotopic signatures of CO_(2)/CH_(4) pairs,it was determined that CH_(4) production in sewers primarily occurred through acetate fermentation.Additionally,the structure of sewer pipes had a significant impact on GHG levels.This study offers valuable insights into the overall GHG emissions associated with sewer networks and sheds ight on themechanismsdriving theseemissions.展开更多
Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic...Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic ions interact with immune cells remains largely unknown.Herein,selecting from a range of cationic and anionic ions,we were excited to discover that MoO_(4)^(2-)could act as a cGAS-STING agonist and further confirmed the capability of Mn^(2+)to activate the cGAS-STING pathway.Inspired by such findings,we synthesized manganese molybdate nanoparticles with polyethylene glycol modification(MMP NDs)for cancer metalloimmunotherapy.Meanwhile,MMP NDs could consume glutathione(GSH)over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses,which was further amplified by MMP-triggered the cGAS-STING activation.In turn,activated CD8+T cells to secrete high levels of interferonγ(IFN-γ)and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation,which constituted a“cycle”of therapy.As a result,the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models.Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.展开更多
Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-target...Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.展开更多
Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating...Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect,the prognosis of patients with melanoma is still suboptimal.During tumor progression,melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment.SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide(NAD+),with versatile biological functions in maintaining cell homeostasis.Nevertheless,whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive.Herein,we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response.We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress.Then,we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo.Mechanistically,SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumorpromoting cytokines.SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal,which relieved the transcriptional repression on IRE1αand induced the activation of the IRE1α-XBP1 axis.Moreover,SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis.Additionally,the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated.Taken together,SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.展开更多
Osteosarcoma(OS)patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis.Magnetic hyperthermia therapy(MHT)combined with immunotherapy is an effective strategy to treat solid ...Osteosarcoma(OS)patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis.Magnetic hyperthermia therapy(MHT)combined with immunotherapy is an effective strategy to treat solid and metastatic tumors.Here,we combined biodegradable magnesium(Mg)macroscale rods,which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field,and immunotherapy to achieve a radical cure for OS.The eddy thermal effect(ETE)of the Mg rods(MgR)showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells(DCs),and the mild MHT induced the immunogenic cell death(ICD)in the OS cells.Combined with immune checkpoint blockade(ICB)therapy,we obtained an excellent curative effect against OS,and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages.Interestingly,the biodegradable MgR also promoted bone osteogenesis.Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment(TME),which would inspire the application of MHT for the effective treatment of OS.展开更多
High-efficiency photocatalytic hydrogen evolution(PHE)relies on the development of inexpensive,stable,and efficient photocatalysts.Cadmium sulfide(CdS),as a typical binary metal sulfide,has attracted considerable rese...High-efficiency photocatalytic hydrogen evolution(PHE)relies on the development of inexpensive,stable,and efficient photocatalysts.Cadmium sulfide(CdS),as a typical binary metal sulfide,has attracted considerable research attention due to its negative conduction band position,narrow band gap for visible-light response,and strong driving force for PHE.However,the construction of CdSbased photocatalysts and the PHE rate still require improvement for practical applications.In this review,recent advances in CdS-based photocatalysts for PHE via water splitting are systematically summarized.First,the semiconductor properties of CdS,including the crystal and band structures,are briefly introduced.Afterward,the fundamental mechanisms of PHE using semiconductor photocatalysts via water splitting are discussed.Subsequently,the photoactivity of bare CdS with different morphologies and structures,CdS with cocatalyst loading,and CdS-based heterojunction photocatalysts are reviewed and discussed in detail.Finally,the challenges and prospects for exploring advanced CdS-based photocatalysts are provided.展开更多
Currently,there are no clinical drugs available to treat acute kidney injury(AKI).Given the high prevalence and high mortality rate of AKI,the development of drugs to effectively treat AKI is a huge unmet medical need...Currently,there are no clinical drugs available to treat acute kidney injury(AKI).Given the high prevalence and high mortality rate of AKI,the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot.Although existing evidence fully demonstrates that reactive oxygen and nitrogen species(RONS)burst at the AKI site is a major contributor to AKI progression,the heterogeneity,complexity,and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects.Recently,nanodrugs with intrinsic kidney targeting through the control of size,shape,and surface properties have opened exciting prospects for the treatment of AKI.Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments.In this review,we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy.First,we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI:hypoxia,harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI.Subsequently,we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI:nano-RONS-sacrificial agents,antioxidant nanozymes,and nanocarriers for antioxidants and anti-inflammatory drugs.These nanodrugs have demonstrated excellent therapeutic effects,such as greatly reducing oxidative stress damage,restoring renal function,and low side effects.Finally,we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.展开更多
This study,grounded in design culture code theory,rigorously explores the multifaceted impact of visual imagery on poster design.Uniting theory with practicality,it dissects the strategic,semiotic,and technical aspect...This study,grounded in design culture code theory,rigorously explores the multifaceted impact of visual imagery on poster design.Uniting theory with practicality,it dissects the strategic,semiotic,and technical aspects of poster creation,illuminating how visual elements are strategically employed,convey nuanced meanings,and adhere to design principles.Notably,it scrutinizes the adaptability of these strategies across diverse socio-cultural contexts.The study enriches our comprehension of how visual choices endow posters with significance and emotional resonance.Furthermore,it contributes novel insights into the technical intricacies of visual design principles.By synthesizing theory and practice,with an emphasis on cross-cultural adaptability,this study advances our understanding of how visual imagery influences strategic,meaningful,and technical dimensions in poster design.It holds implications for design practitioners and offers inspiration for future research in this field.In humility,it contributes to the existing body of knowledge while paving the way for further exploration in the discipline.展开更多
Fe-N-C electrocatalysts,comprising FeN_(4) single atom sites immobilized on N-doped carbon supports,offer excellent activity in the oxygen reduction reaction(ORR),especially in alkaline solution.Herein,we report a sim...Fe-N-C electrocatalysts,comprising FeN_(4) single atom sites immobilized on N-doped carbon supports,offer excellent activity in the oxygen reduction reaction(ORR),especially in alkaline solution.Herein,we report a simple synthetic strategy for improving the accessibility of FeN_(4) sites during ORR and simultaneously fine-tuning the microenvironment of FeN_(4) sites,thus enhancing the ORR activity.Our approach involved a simple one-step pyrolysis of a Fe-containing zeolitic imidazolate framework in the presence of NaCl,yielding a hierarchically porous Fe-N-C electrocatalyst containing tailored FeN_(4) sites with slightly elongated Fe-N bond distances and reduced Fe charge.The porous carbon structure improved mass transport during ORR,whilst the microenvironment optimized FeN_(4) sites benefitted the adsorption/desorption of ORR intermediates.Accordingly,the developed electrocatalyst,possessing a high FeN_(4) site density(9.9×10^(19) sites g^(-1))and turnover frequency(2.26 s^(-1)),delivered remarkable ORR performance with a low overpotential(a half-wave potential of 0.90 V vs.reversible hydrogen electrode)in 0.1 mol L^(-1) KOH.展开更多
基金Supported by Project of Science and Technology Department of Guizhou Province ([2019]1401)Guizhou Administration of Traditional Chinese Medicine (QZYY-2021-03)Guizhou Provincial Health Commission (gzwkj2021-464).
文摘[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.
基金Supported by Project of Science and Technology Department of Guizhou Province([2019]1401ZK[2021]-546)Guizhou Provincial Health Commission(gzwkj2021-464)。
文摘[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.
基金Supported by Project of Science and Technology department of Guizhou Province([2019]1401)Guizhou Administration of Traditional Chinese Medicine(QZYY-2021-03)Guizhou Provincial Health Commission(gzwkj2021-464).
文摘[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and all targets of GAA were predicted by converting 3D model molecules into SMILES online tool and Swiss target prediction.Genecards database and DisGeNET database were used to find the targets related to MI,and then Venny 2.1.0 was used to generate the corresponding Wayne diagram,and then Cytoscape 3.9.1 software was used to construct the protein-protein interaction(PPI)network.With the help of DAVID database and Microbiology,the selected core targets were enriched and analyzed by gene ontology(GO),biological process(BP),and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the molecular docking between GAA and core targets was verified by AutoDock and Pymol software.[Results]A total of 1883 MI targets were screened,and in the protein-protein interaction network,AKT1,PTGS2,PPARG,ESR1,GSK3B were the proteins with higher values.Gene ontology and KEEG enrichment analysis showed that the biological processes involved mainly included inflammatory response,negative regulation of gene expression,and response to exogenous stimuli.Signaling pathways mainly include IL-17 signaling pathway,HIF-1 signaling pathway,and so on.The results of molecular docking showed that the binding energy of GAA and core protein was less than-5 Kcal/mol in four groups.These indicated that GAA with good binding had a certain therapeutic effect on myocardial ischemia.[Conclusions]Based on the systematic network pharmacology method,this study predicts the basic pharmacological effects and potential mechanisms of GAA in the treatment of MI,and reveals that GAA may treat MI through multiple targets and signaling pathways.It is expected to provide a basis for further study of its pharmacological mechanisms.
基金Jilin Province Science and Technology Development Program,Grant/Award Numbers:20180101030JC,20190201270JC,20200201001JCNational Natural Science Foundation of China,Grant/Award Numbers:21633008,21673221,21875243,U1601211+1 种基金Research Innovation Fund,Grant/Award Number:DNL202010Special Funds for Guiding Local Scientific and Technological Development by the Central Government,Grant/Award Number:2020JH6/10500021。
文摘CO impurity-induced catalyst deactivation has long been one of the biggest challenges in proton-exchange membrane fuel cells,with the poisoning phenomenon mainly attributed to the overly strong adsorption on the catalytic site.Here,we present a mechanistic study that overturns this understanding by using Rh-based single-atom catalysis centers as model catalysts.We precisely modulated the chelation structure of the Rh catalyst by coordinating Rh with C or N atoms,and probed the reaction mechanism by surface-enhanced Raman spectroscopy.Direct spectroscopic evidence for intermediates indicates that the reactivity of adsorbed OH^(*),rather than the adsorption strength of CO^(*),dictates the CO electrocatalytic oxidation behavior.The RhN_(4)sites,which adsorb the OH^(*)intermediate more weakly than RhC4 sites,showed prominent CO oxidation activity that not only far exceeded the traditional Pt/C but also the RhC4 sites with similar CO adsorption strength.From this study,it is clear that a paradigm shift in future research should be considered to rationally design high-performance CO electro-oxidation reaction catalysts by sufficiently considering the water-related reaction intermediate during catalysis.
基金Supported by Project of Science and Technology Department of Guizhou Province(ZK[2021]-546)Project of Science and Technology Department of Guizhou Province([2019]1401)+1 种基金Guizhou Administration of Traditional Chinese Medicine(QZYY-2021-03)Guizhou Provincial Health Commission(gzwkj2021-464).
文摘[Objectives]This study was conducted to clarify the action mechanism of Pseudostellariae Radix in regulating angiogenesis by using network pharmacology and a dual-screening system,and to provide a basis for its clinical treatment of cardiovascular diseases.[Methods]The TCMSP database was used for preliminary screening to obtain the active compounds of Pseudostellariae Radix and the protein targets of its action.GeneCards and OMIM databases were used to search for targets related to angiogenesis.Cytoscape 3.9.1 was used to construct a drug-target network and protein interaction network of Pseudostellariae Radix in angiogenesis.The GO enrichment analysis and KEGG pathway analysis of the targets of Pseudostellariae Radix in angiogenesis were carried out on Metascape platform.The effects of the screened active compounds were verified using a dual-screening system.[Results]Six active components of Pseudostellariae Radix,luteolin,acetin,beta-sitosterol,linarin,schottenol and 1-monolinolein,were screened by TCMSP database;and the six active components were predicted with 78 common target proteins related to angiogenesis,of which 19 were core targets.Pseudostellariae Radix mainly intervened in angiogenesis through domain specific binding,ubiquitin-like protein ligase binding,kinase binding and other molecular functions to regulate biological processes such as membrane microdomain,plasma membrane raft and caveola.The results of KEGG enrichment indicated that pathways in cancer,lipid and atherosclerosis,hepatitis B,apoptosis,toxoplasmosis and other key pathways might be the mechanism for the intervention of angiogenesis.The results of the dual-screening system showed that luteolin,acacetin,beta-sitosterol and linarin protected HUVECs and promoted zebrafish angiogenesis.[Conclusions]This study preliminarily demonstrated that luteolin,acacetin,beta-sitosterol and linarin could intervene in angiogenesis through multiple targets and multiple pathways,providing ideas and a scientific basis for the treatment of cardiovascular diseases.
基金Supported by Project of Science and Technology Department of Guizhou Province(ZK[2021]-546)Project of Science and Technology Department of Guizhou Province([2019]1401)+1 种基金Guizhou Administration of Traditional Chinese Medicine(QZYY-2021-03)Guizhou Provincial Health Commission(gzwkj2021-464).
文摘[Objectives]This study was conducted to explore the intervention mechanism of Danggui Buxue Decoction in perimenopausal syndrome based on network pharmacology and molecular docking.[Methods]The chemical components and targets of Danggui Buxue Decoction were acquired through the TCMSP database,and the main targets of perimenopausal syndrome were obtained through the GeneCards database.The component targets and disease targets were intersected,and combining with active components and Chinese herbs in the decoction,a traditional Chinese medicine-component-target network was constructed using Cytoscape 3.7.1 software.The STRING platform was employed for protein-protein interaction analysis.The DAVID analysis platform was used to conduct target GO and KEGG enrichment analysis,so as to predict the action mechanism Danggui Buxue Decoction.Finally,an active component-disease target-signal pathway network diagram was constructed.[Results]Twenty two components in Danggui Buxue Decoction related to perimenopausal syndrome and 120 corresponding targets were obtained,including active components such as 1,7-dihydroxy-3,9-dimquercetin and kaempferol,and key targets such as TNF,ESR1 and PPARG.The results of GO analysis and KEEG analysis indicated that Danggui Buxue Decoction might regulate the transcription of RNA polymerase II promoter,DNA templating,gene expression,signal transduction,hypoxia response and other biological processes by regulating multiple signal pathways such as chemical carcinogenesis-receptor activation,cancer pathways,lipid and atherosclerosis,tryptophan metabolism,malaria,steroid hormone biosynthesis and chemical carcinogenesis-DNA adduct.[Conclusions]Danggui Buxue Decoction intervenes in perimenopausal syndrome through multiple components,targets and pathways,providing a basis for elucidating the intervention mechanism of Danggui Buxue Decoction and expanding its clinical application.
文摘This study aimed to determine the effectiveness of comprehensive rehabilitation for patients with aneurysmal subarachnoid hemorrhage (aSAH) and to explore the factors influencing the prognosis of rehabilitation. This was a retrospective study. Twenty-five patients with aSAH were treated with physical therapy, occupational therapy, speech therapy, cognitive therapy, music therapy, Chinese acupuncture, hyperbaric oxygen, and transcranial magnetic stimulation. The general data of all patients were collected, and the functional scores at admission were compared with those at discharge. The Mini Mental State Examination, Fugl-Meyer Assessment Scale (FMAS) for motor and balance assessment, Holden Functional Ambulation Classification (FAC), modified Rankin Scale, National Institute of Health Stroke Scale, Modified Barthel Index for activities of daily living (ADL), and Glasgow Outcome Scale were significantly improved among 25 patients with aSAH after 1 month of comprehensive rehabilitation training. Hydrocephalus was an independent factor of the ability to perform ADLs (odds ratio, 0.29;95% confidence interval, 2.03. 3.15;p = 0.000). The improvement of ADLs in aSAH patients was not related to sex, surgical method, aneurysm location, age, or smoking status. Comprehensive and professional rehabilitation is effective for the cognition, movement, walking, ADLs, and functional prognosis of patients with aSAH, while early hydrocephalus may be a risk factor for poor ADLs.
基金supported from the National Natural Science Foundation of China,Grant/Award Number:U1732267,21503218.
文摘Cobalt carbide(Co2C)was considered as potential catalysts available for large-scale industrialization of transforming syngas(H2 and CO)to clean fuels.Herein,we successfully synthesized Co-based catalysts with MnO supported,to comprehend the effects of Co2C for Fischer–Tropsch synthesis(FTS)under ambient conditions.The huge variety of product selectivity which was contained by different active sites(Co and Co2C)has been found.Furthermore,density functional theory(DFT)shows that Co2C is efficacious of CO adsorption,whereas is weaker for H adsorption than Co.Combining the advantages of Co and Co2C,the catalyst herein can not only obtain more C5+products but also suppress methane selectivity.It can be a commendable guide for the design of industrial application products in FTS.
基金the Joint Fund of the National Natural Science Foundation of China(U1732267).
文摘Understanding of the oxygen reduction reaction(ORR)mechanism for single atom catalysts is pivotal for the rational design of non-precious metal cathode materials and the commercialization of fuel cells.Herein,a series of non-precious metal electrocatalysts based on nitrogen-doped bimetallic(Fe and Co)carbide were modeled by density functional theory calculations to predict the corresponding reaction pathways.The study elucidated prior oxygen adsorption on the Fe atom in the dual site and the modifier role of Co atoms to tune the electronic structures of Fe.The reaction activity was highly correlated with the bimetallic center and the coordination environment of the adjacent nitrogen.Interestingly,the preadsorption of*OH resulted in the apparent change of metal atoms'electronic states with the d-band center shifting toward the Fermi level,thereby boosting reaction activity.The result should help promote the fundamental understanding of active sites in ORR catalysts and provide an effective approach to the design of highly efficient ORR catalysts on an atomic scale.
基金supported by the financial support from Joint Fund of the National Natural Science Foundation of China(U1732267)the National Natural Science Foundation of China(91545101)
文摘Constructing heterostructure is an important strategy to design efficient electrocatalysts. The synergetic interaction between dissimilar materials has been considered as the origin of the activity enhancement,however, the interfacial interaction is challenging to probe, thus, the underlying mechanism remains obscure. Here, we reported a heterostructured α-MoC/β-Mo2 C electrocatalyst for hydrogen evolution in alkaline media, which shows a significant electrocatalytic activity improvement as compared to the single component. Based on extensive characterizations including high-resolution transmission electron microscopy and X-ray absorption fine structure(XAFS) spectroscopy, together with density functional theory, we unraveled the synergetic interaction between α-MoC and β-Mo2 C, implying that α-Mo C sites are beneficial for water dissociation and hydrogen prefers to release on β-Mo2 C sites.
基金supported by the Innovation Fund of WNLO 2018WNLOKF024,the National Natural Science Foundation of China(U20A20254,52072253)the China Postdoctoral Science Foundation(2021TQ0229,2021M702381)Collaborative Innovation Center of Suzhou Nano Science and Technology,the 111 Project,Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544)。
文摘Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases.In this study,a new type of hydrogen peroxide(H_(2)O_(2)T-activated photoacoustic nanoprobe[Mn-AH nanoscale coordination polymer nanodots(NCPs)]was successfully synthesized by a simple one-step method in water phase containing 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),horse radish peroxidase(HRP),and manganese ion(Mn^(2+).After modification by polyethylene glycol(PEG),Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H_(2)O_(2)-responsive chromogenic assay with great speci¯city and sensitivity.In the presence of H_(2)O_(2),colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared(NIR)absorbance,enabling photoacoustic detection of endogenous H_(2)O_(2).Using H_(2)O_(2)-activated Mn-AH NCPs,we have successfully performed PA imaging and H_(2)O_(2)detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder tumor.Due to the inherent Mn element existence inside the Mn-AH,this nanoprobe also serves as a good T1-weighted magnetic resonance imaging(MRI)contrast agent simultaneously.Lastly,after accomplishing its imaging functions,the Mn-AH NCPs could be cleared out from the body without any long-term toxicity,providing a new opportunity for cancer diagnosis and treatment.
基金financially supported by the National Key Research and Development Program of China(No.2022YFC3203202-3)the Shenzhen Science and Technology Innovation Commission(No.KCXFZ20211020163556020).
文摘Sewer networks play a vital role in sewage collection and transportation,and they are being rapidly expanded.However,the microbial processes occurring within these networks have emerged as significant contributors to greenhouse gas(GHG)emissions.Compared to that from other sectors,our understanding of the magnitude of GHG emissions from sewer networks is currently limited.In this study,we conducted a GHG emission assessment in an independent sewer network located in Beijing,China.The findings revealed annual emissions of 62.3 kg CH_(4) and 0.753 kg N20.CH_(4) emerged as the primary GHG emitted from sewers,accounting for 87.4%of the total GHG emissions.Interestingly,compared with main pipes,branch pipes were responsible for a larger share of GHG emissions,contributing to 76.7%of the total.A GHG emission factor of 0.26 kg CO_(2)-eq/(m:yr)was established to quantify sewer GHG emissions.By examining the isotopic signatures of CO_(2)/CH_(4) pairs,it was determined that CH_(4) production in sewers primarily occurred through acetate fermentation.Additionally,the structure of sewer pipes had a significant impact on GHG levels.This study offers valuable insights into the overall GHG emissions associated with sewer networks and sheds ight on themechanismsdriving theseemissions.
基金supported by the National Research Programs of China(2022YFB3804604,2021YFF0701800)National Natural Science Foundation of China(U20A20254,52072253)+2 种基金Collaborative Innovation Center of Suzhou Nano Science and Technology,the 111 Project,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,a Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544)Jiangsu Social Development Project(BE2019658)Suzhou Key Laboratory of Nanotechnology and Biomedicine.The authors also thank the website app.Biorender.com for the assistance in creating the Figures.
文摘Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic ions interact with immune cells remains largely unknown.Herein,selecting from a range of cationic and anionic ions,we were excited to discover that MoO_(4)^(2-)could act as a cGAS-STING agonist and further confirmed the capability of Mn^(2+)to activate the cGAS-STING pathway.Inspired by such findings,we synthesized manganese molybdate nanoparticles with polyethylene glycol modification(MMP NDs)for cancer metalloimmunotherapy.Meanwhile,MMP NDs could consume glutathione(GSH)over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses,which was further amplified by MMP-triggered the cGAS-STING activation.In turn,activated CD8+T cells to secrete high levels of interferonγ(IFN-γ)and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation,which constituted a“cycle”of therapy.As a result,the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models.Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.
基金National Natural Science Foundation of China(No.81974508,21974134)Hunan Science Fund for Distinguished Young Scholar of China(No.2021JJ10067)+3 种基金Innovation-Driven Project of Central South University(No.202045005)Hunan Provincial Natural Science Foundation of China(No.2021JJ31066)Key Research Project of Ningxia Hui Autonomous Region in 2021 of China(Major Project)(No.2021BEG01001)Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).
文摘Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.
基金The research leading to these results has received funding from National Natural Science Foundation of China(No.81902791,82173395)Support Program of Young Talents in Shaanxi Province(No.20200303,No.2022SF-178)Young Eagle Project of Fourth Military Medical University(No.2019cyjhgwn).
文摘Melanoma is the most lethal type of skin cancer,originating from the malignant transformation of melanocyte.While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect,the prognosis of patients with melanoma is still suboptimal.During tumor progression,melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment.SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide(NAD+),with versatile biological functions in maintaining cell homeostasis.Nevertheless,whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive.Herein,we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response.We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress.Then,we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo.Mechanistically,SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumorpromoting cytokines.SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal,which relieved the transcriptional repression on IRE1αand induced the activation of the IRE1α-XBP1 axis.Moreover,SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis.Additionally,the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated.Taken together,SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.
基金This article was partially supported by the National Natural Science Foundation of China(U20A20254,52072253,82172506,82030068)Collaborative Innovation Center of Suzhou Nano Science and Technology,the 111 Project,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,a Jiangsu Social Development Project(BE2019658)+1 种基金a Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544)Suzhou Key Laboratory of Nanotechnology and Biomedicine.L.Cheng was supported by the Tang Scholarship of Soochow University.
文摘Osteosarcoma(OS)patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis.Magnetic hyperthermia therapy(MHT)combined with immunotherapy is an effective strategy to treat solid and metastatic tumors.Here,we combined biodegradable magnesium(Mg)macroscale rods,which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field,and immunotherapy to achieve a radical cure for OS.The eddy thermal effect(ETE)of the Mg rods(MgR)showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells(DCs),and the mild MHT induced the immunogenic cell death(ICD)in the OS cells.Combined with immune checkpoint blockade(ICB)therapy,we obtained an excellent curative effect against OS,and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages.Interestingly,the biodegradable MgR also promoted bone osteogenesis.Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment(TME),which would inspire the application of MHT for the effective treatment of OS.
基金the Natural Science Foundation of Hainan Province(grant no.521RC495)the National Natural Science Foundation of China(grant nos.22109034,22109035,52164028,and 62105083)+1 种基金the Foundation of State Key Laboratory of Marine Resource Utilization in South China Sea(Hainan University,grant no.MRUKF2021029)the Start-up Research Foundation of Hainan University(grant nos.KYQD(ZR)-20008,20082,20083,20084,21065,21124,and 21125).
文摘High-efficiency photocatalytic hydrogen evolution(PHE)relies on the development of inexpensive,stable,and efficient photocatalysts.Cadmium sulfide(CdS),as a typical binary metal sulfide,has attracted considerable research attention due to its negative conduction band position,narrow band gap for visible-light response,and strong driving force for PHE.However,the construction of CdSbased photocatalysts and the PHE rate still require improvement for practical applications.In this review,recent advances in CdS-based photocatalysts for PHE via water splitting are systematically summarized.First,the semiconductor properties of CdS,including the crystal and band structures,are briefly introduced.Afterward,the fundamental mechanisms of PHE using semiconductor photocatalysts via water splitting are discussed.Subsequently,the photoactivity of bare CdS with different morphologies and structures,CdS with cocatalyst loading,and CdS-based heterojunction photocatalysts are reviewed and discussed in detail.Finally,the challenges and prospects for exploring advanced CdS-based photocatalysts are provided.
基金This work was supported by the National Natural Science Foundation of China,China(No.81974508,21974134)the Hunan Science Fund for Distinguished Young Scholar(No.2021JJ10067)+2 种基金Innovation-Driven Project of Central South University(No.202045005),Hunan Provincial Natural Science Foundation of China(No.2021JJ31066)Key Research Project of Ningxia Hui Autonomous Region in 2021(Major Project)(No.2021BEG01001)The Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).
文摘Currently,there are no clinical drugs available to treat acute kidney injury(AKI).Given the high prevalence and high mortality rate of AKI,the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot.Although existing evidence fully demonstrates that reactive oxygen and nitrogen species(RONS)burst at the AKI site is a major contributor to AKI progression,the heterogeneity,complexity,and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects.Recently,nanodrugs with intrinsic kidney targeting through the control of size,shape,and surface properties have opened exciting prospects for the treatment of AKI.Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments.In this review,we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy.First,we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI:hypoxia,harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI.Subsequently,we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI:nano-RONS-sacrificial agents,antioxidant nanozymes,and nanocarriers for antioxidants and anti-inflammatory drugs.These nanodrugs have demonstrated excellent therapeutic effects,such as greatly reducing oxidative stress damage,restoring renal function,and low side effects.Finally,we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.
文摘This study,grounded in design culture code theory,rigorously explores the multifaceted impact of visual imagery on poster design.Uniting theory with practicality,it dissects the strategic,semiotic,and technical aspects of poster creation,illuminating how visual elements are strategically employed,convey nuanced meanings,and adhere to design principles.Notably,it scrutinizes the adaptability of these strategies across diverse socio-cultural contexts.The study enriches our comprehension of how visual choices endow posters with significance and emotional resonance.Furthermore,it contributes novel insights into the technical intricacies of visual design principles.By synthesizing theory and practice,with an emphasis on cross-cultural adaptability,this study advances our understanding of how visual imagery influences strategic,meaningful,and technical dimensions in poster design.It holds implications for design practitioners and offers inspiration for future research in this field.In humility,it contributes to the existing body of knowledge while paving the way for further exploration in the discipline.
基金supported by a James Cook Research Fellowship,administered by the Royal Society Te Apārangifunding support from Greg and Kathryn Trounson,the Energy Education Trust of New Zealand,the Mac Diarmid Institute for Advanced Materials and Nanotechnology,the National Key Projects for Fundamental Research and Development of China(2017YFA0206904 and 2017YFA0206900)+1 种基金the National Natural Science Foundation of China(51825205 and 21871279)the Beijing Natural Science Foundation(2191002)。
文摘Fe-N-C electrocatalysts,comprising FeN_(4) single atom sites immobilized on N-doped carbon supports,offer excellent activity in the oxygen reduction reaction(ORR),especially in alkaline solution.Herein,we report a simple synthetic strategy for improving the accessibility of FeN_(4) sites during ORR and simultaneously fine-tuning the microenvironment of FeN_(4) sites,thus enhancing the ORR activity.Our approach involved a simple one-step pyrolysis of a Fe-containing zeolitic imidazolate framework in the presence of NaCl,yielding a hierarchically porous Fe-N-C electrocatalyst containing tailored FeN_(4) sites with slightly elongated Fe-N bond distances and reduced Fe charge.The porous carbon structure improved mass transport during ORR,whilst the microenvironment optimized FeN_(4) sites benefitted the adsorption/desorption of ORR intermediates.Accordingly,the developed electrocatalyst,possessing a high FeN_(4) site density(9.9×10^(19) sites g^(-1))and turnover frequency(2.26 s^(-1)),delivered remarkable ORR performance with a low overpotential(a half-wave potential of 0.90 V vs.reversible hydrogen electrode)in 0.1 mol L^(-1) KOH.