Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
This work presents a high-stability self-rectifying memristor(SRM)array based on the Pt/TaO_(x)/Ti structure,with an indepth investigation of the performance and potential applications of the device.The device demonst...This work presents a high-stability self-rectifying memristor(SRM)array based on the Pt/TaO_(x)/Ti structure,with an indepth investigation of the performance and potential applications of the device.The device demonstrates excellent rectification and on/off ratios,along with low-power readout,multi-state storage,and multi-level switching capabilities,highlighting its practicality and adaptability.Notably,the device exhibits outstanding fluctuation suppression and exceptional uniformity.The coefficient of variation(CV)of the rectification ratio,calculated as 0.11497 at 3 V,indicates its high stability under multiple cycles and low-voltage operation,making it well-suited for large-scale integration and operational applications.Moreover,the stability of the rectification ratio further reinforces its potential as a hardware foundation for large-scale inmemory computing systems.By combining the neuromorphic characteristics of the device with a simulated annealing algorithm and optimizing the annealing temperature function,the system emulates biological neuron behavior,enabling fast and efficient image restoration tasks.Experimental results demonstrate that this approach significantly outperforms traditional algorithms in both optimization speed and repair accuracy.The present study offers a novel perspective for the design of in-memory computing hardware and showcases promising applications in neuromorphic computing and image processing.展开更多
Conventional error cancellation approaches separate molecules into smaller fragments and sum the errors of all fragments to counteract the overall computational error of the parent molecules.However,these approaches m...Conventional error cancellation approaches separate molecules into smaller fragments and sum the errors of all fragments to counteract the overall computational error of the parent molecules.However,these approaches may be ineffective for systems with strong localized chemical effects,as fragmenting specific substructures into simpler chemical bonds can introduce additional errors instead of mitigating them.To address this issue,we propose the Substructure-Preserved Connection-Based Hierarchy(SCBH),a method that automatically identifies and freezes substructures with significant local chemical effects prior to molecular fragmentation.The SCBH is validated by the gas-phase enthalpy of formation calculation of CHNO molecules.Therein,based on the atomization scheme,the reference and test values are derived at the levels of Gaussian-4(G4)and M062X/6-31+G(2df,p),respectively.Compared to commonly used approaches,SCBH reduces the average computational error by half and requires only15%of the computational cost of G4 to achieve comparable accuracy.Since different types of local effect structures have differentiated influences on gas-phase enthalpy of formation,substituents with strong electronic effects should be retained preferentially.SCBH can be readily extended to diverse classes of organic compounds.Its workflow and source code allow flexible customization of molecular moieties,including azide,carboxyl,trinitromethyl,phenyl,and others.This strategy facilitates accurate,rapid,and automated computations and corrections,making it well-suited for high-throughput molecular screening and dataset construction for gas-phase enthalpy of formation.展开更多
Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcoh...Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.展开更多
High-entropy alloy(HEA)nanoparticles(NPs)have attracted great attention in electrocatalysis due to their tailorable complex compositions and unique properties.Herein,we introduce Fe,Co,Ni,Cr and Mn into the metal-poly...High-entropy alloy(HEA)nanoparticles(NPs)have attracted great attention in electrocatalysis due to their tailorable complex compositions and unique properties.Herein,we introduce Fe,Co,Ni,Cr and Mn into the metal-polyphenol coordination system to prepare HEA NPs enclosed in N-doped carbon(FeCoNiCrMn)with great potential for catalyzing oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).The unique high-entropy structural characteristics in FeCoNiCrMn facilitate effective interplay between metal species,leading to improved ORR(E_(1/2)=0.89 V)and OER(η=330 mV,j=10 mA·cm^(−2))activity.Additionally,FeCoNiCrMn exhibits excellent open-circuit voltage(1.523 V),power density(110 mW·cm^(−2))and long-term durability,outperforming Pt/C+IrO_(2) electrodes as a cathode catalyst in Zn-air batteries(ZABs).Such polyphenol-assisted alloying method broadens and simplifies the development of HEA electrocatalysts for high-performance ZABs.展开更多
As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the i...As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.展开更多
Metal foams are a fascinating group of materials that possess distinct physicochEMIcal properties and interconnected strut features with high surface area-to-volume ratios, high specific strength and lightweight natur...Metal foams are a fascinating group of materials that possess distinct physicochEMIcal properties and interconnected strut features with high surface area-to-volume ratios, high specific strength and lightweight nature. These characteristics make them ideal for applications in vibration damping, heat insulation and weight reduction. In recent years, there has been increasing interest in the application of interfering energy conversion such as electromagnetic wave (EMW) and sound, where the metal foams could emerge as a solution. This paper will present a comprehensive review of the preparation methods as well as the interference energy converting mechanisms for metal foams. Typically, the progress and prospective aspects of metal foams for EMW absorption, electromagnetic interference (EMI) shielding and sound absorption have been emphasized. Through this review, we aspire to offer valuable insights for the development of multifunctional applications with metal foam materials.展开更多
Dual-ion batteries(DIBs)usually use carbon-based materials as electrodes,showing advantages in high operating volt-age,potential low cost,and environmental friendliness.Different from conventional“rocking chair”type...Dual-ion batteries(DIBs)usually use carbon-based materials as electrodes,showing advantages in high operating volt-age,potential low cost,and environmental friendliness.Different from conventional“rocking chair”type secondary batter-ies,DIBs perform a unique working mechanism,which employ both cation and anion taking part in capacity contribution at an anode and a cathode,respectively,during electrochemical reactions.Graphite has been identified as a suitable cathode material for anion intercalation at high voltages(>4.8 V)with fast reaction kinetics.However,the development of DIBs is being hindered by dynamic mismatch between a cathode and an anode due to sluggish Li+diffusion at a high rate.Herein,we prepared phyllostachys edulis derived carbon(PEC)through microstructure regulation strategy and investigated the carbonized temperature effect,which effectively tailored the rich short-range ordered graphite microdomains and disor-dered amorphous regions,as well as a unique nano-pore hierarchical structure.The pore size distribution of nano-pores was concentrated in 0.5-5 nm,providing suitable channels for rapid Li+transportation.It was found that PEC-500(carbon-ized at 500℃)achieved a high capacity of 436 mAh·g^(-1)at 300 mA·g^(-1)and excellent rate performance(maintaining a high capacity of 231 mAh·g^(-1)at 3 A·g^(-1)).The assembled dual-carbon PEC-500||graphite full battery delivered 114 mAh·g^(-1)at 10 C with 96%capacity retention after 3000 cycles and outstanding rate capability,providing 74 mAh·g^(-1)at 50 C.展开更多
Strength and plasticity of metallic structural materials are the fundamental indicators of the service reliability[1].However,as is well known,a general trade-offrelationship exists between strength and plasticity of ...Strength and plasticity of metallic structural materials are the fundamental indicators of the service reliability[1].However,as is well known,a general trade-offrelationship exists between strength and plasticity of metallic materials,making it difficult to improve both of them synchronously[2].At present,only few of the successful cases[3-8],achieved via nano-particles[7],heterogeneous microstructures[8],etc.are mostly limited to some specific materials or processes.展开更多
By manipulating the distribution of surface electrons,defect engineering enables effective control over the adsorption energy between adsorbates and active sites in the CO_(2)reduction reaction(CO_(2)RR).Herein,we rep...By manipulating the distribution of surface electrons,defect engineering enables effective control over the adsorption energy between adsorbates and active sites in the CO_(2)reduction reaction(CO_(2)RR).Herein,we report a hollow indium oxide nanotube containing both oxygen vacancy and sulfur doping(V_o-Sx-In_(2)O_(3))for improved CO_(2)-to-HCOOH electroreduction and Zn-CO_(2)battery.The componential synergy significantly reduces the*OCHO formation barrier to expedite protonation process and creates a favorable electronic micro-environment for*HCOOH desorption.As a result,the CO_(2)RR performance of Vo-Sx-In_(2)O_(3)outperforms Pure-In_(2)O_(3)and V_o-In_(2)O_(3),where V_o-S53-In_(2)O_(3)exhibits a maximal HCOOH Faradaic efficiency of 92.4%at-1,2 V vs.reversible hydrogen electrode(RHE)in H-cell and above 92%over a wide window potential with high current density(119.1 mA cm^(-2)at-1.1 V vs.RHE)in flow cell.Furthermore,the rechargeable Zn-CO_(2)battery utilizing V_o-S53-In_(2)O_(3)as cathode shows a high power density of 2.29 mW cm^(-2)and a long-term stability during charge-discharge cycles.This work provides a valuable perspective to elucidate co-defective catalysts in regulating the intermediates for efficient CO_(2)RR.展开更多
For an improved understanding of gas enrichment mechanism in the eastern Sichuan Basin,South China,twelve natural gas samples were obtained from carbonate reservoirs of the Upper Permian strata to analyze the hydrocar...For an improved understanding of gas enrichment mechanism in the eastern Sichuan Basin,South China,twelve natural gas samples were obtained from carbonate reservoirs of the Upper Permian strata to analyze the hydrocarbon and non-hydrocarbon gas compositions,stable carbon and hydrogen isotopes ratios of hydrocarbons,and noble gas isotope ratios.The gas samples in the Upper Permian reservoirs principally consist of alkane gas with a dryness ratio ranging from 127.9 to 1564.4.The carbon isotope ratio of methane(δ^(13)C_(1))was almost constant at-34.1 to-31.3‰,but the carbon isotope ratio of ethane(δ^(13)C2)varied from-36.6‰to-25.8‰.The hydrogen isotope ratio of methane(δ^2HC_(1))also displayed a wide range from-137‰to-127‰.The large variations in the dryness ratio,δ^(13)C_(2),andδ^2HC_(1)with almost constantδ^(13)C_(1)suggest the mixing of sapropelic and humic origins for hydrocarbon gases in these reservoirs.A high concentration of hydrogen sulfide(H_(2)S)originated from the thermochemical sulfate reduction(TSR),which was positively correlated withδ^(13)C_(1)(orδ^(13)C_(2))in individual gas fields.TSR alteredδ^(13)C_(1)(orδ^(13)C_(2))and resulted in the abnormal character of isotopic reversal in the individual samples.Theδ^(13)C_(1)(orδ^(13)C_(2))in most gas samples,independent of H_(2)S concentration,further displayed reversed carbon isotopes because of the mixture of thermogenic gases with various thermal maturity levels.The measured argon isotope ratio(^(40)Ar/^(36)Ar)varied from 310 to 1225,which suggests that the oldest 320 Ma source rock age corresponds to Permian shales.The analysis of the gas origin and the identification of primary source rock have made a significant contribution to further understanding the resource potential and distribution of natural gas in the Upper Permian,and have great implications for gas exploration in the eastern Sichuan Basin.展开更多
Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenol...Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.展开更多
By encapsulating nanoscale particles of goethite(α-FeO(OH)),hydrous ceric oxide(CeO_(2)·H_(2)O,HCO)and silver nanoparticles(AgNPs)in the pores of polystyrene anion exchanger D201,a novel nanocomposite FeO(OH)-HC...By encapsulating nanoscale particles of goethite(α-FeO(OH)),hydrous ceric oxide(CeO_(2)·H_(2)O,HCO)and silver nanoparticles(AgNPs)in the pores of polystyrene anion exchanger D201,a novel nanocomposite FeO(OH)-HCO-Ag-D201 was prepared for the effective removal of arsenic from water.The isotherm study shows that FeO(OH)-HCO-Ag-D201 has excellent adsorption performance for As(III)and As(V),with an increased adsorption capacity of As(III)to 40.12 mg/g compared to that of 22.03 mg/g by the composite adsorbent without AgNPs(FeO(OH)-HCO-D201).The adsorption kinetics data showed that the sorption rate of FeO(OH)-HCO-Ag-D201 for As(III)is less than that for As(V),and the adsorption of As(III)and As(V)were consistent with the pseudo-second-order model and the pseudofirst-order model,respectively.Neutral or basic conditions are favored for the adsorption of As(III/V)by FeO(OH)-HCO-Ag-D201.Compared with nitrate/chloride/bicarbonate,sulfate/silicate/phosphate showed more remarkable inhibition of arsenic removal by FeO(OH)-HCO-Ag-D201,whereas natural organic matter showed no interference to the arsenic removal.The As(V)adsorption involved different interactions such as electrostatic attraction and surface complexation,while the adsorption of As(III)involved the part oxidization of As(III)to As(V)and the simultaneous adsorption of As(III)and As(V).In addition to the Ce(IV)in CeO_(2)·H_(2)O acted as an oxidant,the synergistic effect ofα-FeO(OH)and AgNPs also contributed to the oxidization of As(III)to As(V).Moreover,the reusable property suggested that this FeO(OH)-HCO-Ag-D201 nanocomposite has great potential for arsenic-contaminated water purification.展开更多
The safety of the initial support during the construction of inclined shafts in tunnels traversing through high-hydraulic-pressure surrounding rocks is paramount.This study examines a high-hydraulic-pressure inclined ...The safety of the initial support during the construction of inclined shafts in tunnels traversing through high-hydraulic-pressure surrounding rocks is paramount.This study examines a high-hydraulic-pressure inclined shaft of a tunnel in Western Sichuan Province to analyze the damage characteristics of the initial support and propose a radial drainage and decompression treatment method.Field monitoring was conducted to assess the load and deformation of the initial support structure,and on-site investigations identified the distribution of cracked areas.In addition,numerical simulations were performed to evaluate the force and deformation characteristics of the initial support structure,which were then compared with field observations for validation.The variations in the lateral pressure coefficient and water pressure were evaluated.The results revealed that damage was primarily concentrated in the shoulder,spring line,and knee areas,with the bending moment at the knee increasing by up to 66.9%.The application of the radial drainage and decompression treatment method effectively reduced water pressure loads on the initial support.Post-treatment analysis indicated significant reductions in axial force and bending moment,enhancing structural stability.These findings provide valuable insights for improving the safety and durability of initial support systems in inclined shafts of high-hydraulicpressure railroad tunnels.展开更多
Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely li...Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.展开更多
Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces pati...Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金the National Natural Science Foundation of China(No.U23A20322)the National Key Research and Development Program of China(Nos.2023YFF0719600,2021YFA1202600,and 2021YFB4000800)+4 种基金the CAS Project for Young Scientists in Basic Research(No.YSBR-113)the Ningbo Technology Project(No.2022A-007-C)the Hunan Provincial Natural Science Foundation(Nos.2023JJ50009,2025JJ60351,and 2023JJ30599)the Foundation of Innovation Center of Radiation Application(No.KFZC2023020701)the Major Scientific and Technological Innovation Platform Project of Hunan Province(No.2024JC1003).
文摘This work presents a high-stability self-rectifying memristor(SRM)array based on the Pt/TaO_(x)/Ti structure,with an indepth investigation of the performance and potential applications of the device.The device demonstrates excellent rectification and on/off ratios,along with low-power readout,multi-state storage,and multi-level switching capabilities,highlighting its practicality and adaptability.Notably,the device exhibits outstanding fluctuation suppression and exceptional uniformity.The coefficient of variation(CV)of the rectification ratio,calculated as 0.11497 at 3 V,indicates its high stability under multiple cycles and low-voltage operation,making it well-suited for large-scale integration and operational applications.Moreover,the stability of the rectification ratio further reinforces its potential as a hardware foundation for large-scale inmemory computing systems.By combining the neuromorphic characteristics of the device with a simulated annealing algorithm and optimizing the annealing temperature function,the system emulates biological neuron behavior,enabling fast and efficient image restoration tasks.Experimental results demonstrate that this approach significantly outperforms traditional algorithms in both optimization speed and repair accuracy.The present study offers a novel perspective for the design of in-memory computing hardware and showcases promising applications in neuromorphic computing and image processing.
基金the support of the National Natural Science Foundation of China(22575230)。
文摘Conventional error cancellation approaches separate molecules into smaller fragments and sum the errors of all fragments to counteract the overall computational error of the parent molecules.However,these approaches may be ineffective for systems with strong localized chemical effects,as fragmenting specific substructures into simpler chemical bonds can introduce additional errors instead of mitigating them.To address this issue,we propose the Substructure-Preserved Connection-Based Hierarchy(SCBH),a method that automatically identifies and freezes substructures with significant local chemical effects prior to molecular fragmentation.The SCBH is validated by the gas-phase enthalpy of formation calculation of CHNO molecules.Therein,based on the atomization scheme,the reference and test values are derived at the levels of Gaussian-4(G4)and M062X/6-31+G(2df,p),respectively.Compared to commonly used approaches,SCBH reduces the average computational error by half and requires only15%of the computational cost of G4 to achieve comparable accuracy.Since different types of local effect structures have differentiated influences on gas-phase enthalpy of formation,substituents with strong electronic effects should be retained preferentially.SCBH can be readily extended to diverse classes of organic compounds.Its workflow and source code allow flexible customization of molecular moieties,including azide,carboxyl,trinitromethyl,phenyl,and others.This strategy facilitates accurate,rapid,and automated computations and corrections,making it well-suited for high-throughput molecular screening and dataset construction for gas-phase enthalpy of formation.
基金supported by the National Natural Science Foundation of China(No.31972977)。
文摘Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.
基金supported by the Fundamental Research Funds for the Central Universities(No.22120230104).
文摘High-entropy alloy(HEA)nanoparticles(NPs)have attracted great attention in electrocatalysis due to their tailorable complex compositions and unique properties.Herein,we introduce Fe,Co,Ni,Cr and Mn into the metal-polyphenol coordination system to prepare HEA NPs enclosed in N-doped carbon(FeCoNiCrMn)with great potential for catalyzing oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).The unique high-entropy structural characteristics in FeCoNiCrMn facilitate effective interplay between metal species,leading to improved ORR(E_(1/2)=0.89 V)and OER(η=330 mV,j=10 mA·cm^(−2))activity.Additionally,FeCoNiCrMn exhibits excellent open-circuit voltage(1.523 V),power density(110 mW·cm^(−2))and long-term durability,outperforming Pt/C+IrO_(2) electrodes as a cathode catalyst in Zn-air batteries(ZABs).Such polyphenol-assisted alloying method broadens and simplifies the development of HEA electrocatalysts for high-performance ZABs.
基金financially supported by the National Key Research and Development Program of China(2023YFD2000701)the Natural Science Foundation of Heilongjiang Province,China(YQ2023C011)+1 种基金the Key Research and Development Program of Heilongjiang Province,China(Grant no.2022ZX01A24)the Key Laboratory of Low-carbon Green Agriculture in Northeastern China,Ministry of Agriculture and Rural Affairs of China(LCGANE14)。
文摘As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.
基金supported by the National Natural Science Foundation of China(No.52271180)the Leading Goose R&D Program of Zhejiang Province(2022C01110).
文摘Metal foams are a fascinating group of materials that possess distinct physicochEMIcal properties and interconnected strut features with high surface area-to-volume ratios, high specific strength and lightweight nature. These characteristics make them ideal for applications in vibration damping, heat insulation and weight reduction. In recent years, there has been increasing interest in the application of interfering energy conversion such as electromagnetic wave (EMW) and sound, where the metal foams could emerge as a solution. This paper will present a comprehensive review of the preparation methods as well as the interference energy converting mechanisms for metal foams. Typically, the progress and prospective aspects of metal foams for EMW absorption, electromagnetic interference (EMI) shielding and sound absorption have been emphasized. Through this review, we aspire to offer valuable insights for the development of multifunctional applications with metal foam materials.
基金supported by the National Natural Science Foundation of China(Grant Nos.52272208,22309057)the Natural Science Foundation of Hubei Province(Grant No.2023AFB355)the Fundamental Research Funds for the Central Universities of China(Grant No.2662022LXQD001).
文摘Dual-ion batteries(DIBs)usually use carbon-based materials as electrodes,showing advantages in high operating volt-age,potential low cost,and environmental friendliness.Different from conventional“rocking chair”type secondary batter-ies,DIBs perform a unique working mechanism,which employ both cation and anion taking part in capacity contribution at an anode and a cathode,respectively,during electrochemical reactions.Graphite has been identified as a suitable cathode material for anion intercalation at high voltages(>4.8 V)with fast reaction kinetics.However,the development of DIBs is being hindered by dynamic mismatch between a cathode and an anode due to sluggish Li+diffusion at a high rate.Herein,we prepared phyllostachys edulis derived carbon(PEC)through microstructure regulation strategy and investigated the carbonized temperature effect,which effectively tailored the rich short-range ordered graphite microdomains and disor-dered amorphous regions,as well as a unique nano-pore hierarchical structure.The pore size distribution of nano-pores was concentrated in 0.5-5 nm,providing suitable channels for rapid Li+transportation.It was found that PEC-500(carbon-ized at 500℃)achieved a high capacity of 436 mAh·g^(-1)at 300 mA·g^(-1)and excellent rate performance(maintaining a high capacity of 231 mAh·g^(-1)at 3 A·g^(-1)).The assembled dual-carbon PEC-500||graphite full battery delivered 114 mAh·g^(-1)at 10 C with 96%capacity retention after 3000 cycles and outstanding rate capability,providing 74 mAh·g^(-1)at 50 C.
基金financially supported by the National Natural Science Foundation of China(NSFC)(Nos.52371084,52301177,52322105,52130002,and 52321001)the Youth Innovation Promotion Association CAS(No.2021192)+1 种基金the IMR Innovation Fund(No.2023-ZD01)the Fund of Science and Technology on Surface Physics and Chemistry Laboratory(No.XKFZ202303).
文摘Strength and plasticity of metallic structural materials are the fundamental indicators of the service reliability[1].However,as is well known,a general trade-offrelationship exists between strength and plasticity of metallic materials,making it difficult to improve both of them synchronously[2].At present,only few of the successful cases[3-8],achieved via nano-particles[7],heterogeneous microstructures[8],etc.are mostly limited to some specific materials or processes.
基金supported by the Fundamental Research Funds for the Central Universities(22120230104).
文摘By manipulating the distribution of surface electrons,defect engineering enables effective control over the adsorption energy between adsorbates and active sites in the CO_(2)reduction reaction(CO_(2)RR).Herein,we report a hollow indium oxide nanotube containing both oxygen vacancy and sulfur doping(V_o-Sx-In_(2)O_(3))for improved CO_(2)-to-HCOOH electroreduction and Zn-CO_(2)battery.The componential synergy significantly reduces the*OCHO formation barrier to expedite protonation process and creates a favorable electronic micro-environment for*HCOOH desorption.As a result,the CO_(2)RR performance of Vo-Sx-In_(2)O_(3)outperforms Pure-In_(2)O_(3)and V_o-In_(2)O_(3),where V_o-S53-In_(2)O_(3)exhibits a maximal HCOOH Faradaic efficiency of 92.4%at-1,2 V vs.reversible hydrogen electrode(RHE)in H-cell and above 92%over a wide window potential with high current density(119.1 mA cm^(-2)at-1.1 V vs.RHE)in flow cell.Furthermore,the rechargeable Zn-CO_(2)battery utilizing V_o-S53-In_(2)O_(3)as cathode shows a high power density of 2.29 mW cm^(-2)and a long-term stability during charge-discharge cycles.This work provides a valuable perspective to elucidate co-defective catalysts in regulating the intermediates for efficient CO_(2)RR.
基金supported by the National Natural Science Foundation of China(Nos.42072184 and 41702157)the Science and Technology Cooperation Project of the CNPC-SWPU Innovation Alliance。
文摘For an improved understanding of gas enrichment mechanism in the eastern Sichuan Basin,South China,twelve natural gas samples were obtained from carbonate reservoirs of the Upper Permian strata to analyze the hydrocarbon and non-hydrocarbon gas compositions,stable carbon and hydrogen isotopes ratios of hydrocarbons,and noble gas isotope ratios.The gas samples in the Upper Permian reservoirs principally consist of alkane gas with a dryness ratio ranging from 127.9 to 1564.4.The carbon isotope ratio of methane(δ^(13)C_(1))was almost constant at-34.1 to-31.3‰,but the carbon isotope ratio of ethane(δ^(13)C2)varied from-36.6‰to-25.8‰.The hydrogen isotope ratio of methane(δ^2HC_(1))also displayed a wide range from-137‰to-127‰.The large variations in the dryness ratio,δ^(13)C_(2),andδ^2HC_(1)with almost constantδ^(13)C_(1)suggest the mixing of sapropelic and humic origins for hydrocarbon gases in these reservoirs.A high concentration of hydrogen sulfide(H_(2)S)originated from the thermochemical sulfate reduction(TSR),which was positively correlated withδ^(13)C_(1)(orδ^(13)C_(2))in individual gas fields.TSR alteredδ^(13)C_(1)(orδ^(13)C_(2))and resulted in the abnormal character of isotopic reversal in the individual samples.Theδ^(13)C_(1)(orδ^(13)C_(2))in most gas samples,independent of H_(2)S concentration,further displayed reversed carbon isotopes because of the mixture of thermogenic gases with various thermal maturity levels.The measured argon isotope ratio(^(40)Ar/^(36)Ar)varied from 310 to 1225,which suggests that the oldest 320 Ma source rock age corresponds to Permian shales.The analysis of the gas origin and the identification of primary source rock have made a significant contribution to further understanding the resource potential and distribution of natural gas in the Upper Permian,and have great implications for gas exploration in the eastern Sichuan Basin.
基金supported by Key Research and Development Program of Hubei Province(2022BBA0072)Applied Fundamental Frontier Project of Wuhan Science and Technology Bureau(2020020601012271)。
文摘Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.
基金supported by the National Key Research and Development Program of China(No.2022YFA1205601).
文摘By encapsulating nanoscale particles of goethite(α-FeO(OH)),hydrous ceric oxide(CeO_(2)·H_(2)O,HCO)and silver nanoparticles(AgNPs)in the pores of polystyrene anion exchanger D201,a novel nanocomposite FeO(OH)-HCO-Ag-D201 was prepared for the effective removal of arsenic from water.The isotherm study shows that FeO(OH)-HCO-Ag-D201 has excellent adsorption performance for As(III)and As(V),with an increased adsorption capacity of As(III)to 40.12 mg/g compared to that of 22.03 mg/g by the composite adsorbent without AgNPs(FeO(OH)-HCO-D201).The adsorption kinetics data showed that the sorption rate of FeO(OH)-HCO-Ag-D201 for As(III)is less than that for As(V),and the adsorption of As(III)and As(V)were consistent with the pseudo-second-order model and the pseudofirst-order model,respectively.Neutral or basic conditions are favored for the adsorption of As(III/V)by FeO(OH)-HCO-Ag-D201.Compared with nitrate/chloride/bicarbonate,sulfate/silicate/phosphate showed more remarkable inhibition of arsenic removal by FeO(OH)-HCO-Ag-D201,whereas natural organic matter showed no interference to the arsenic removal.The As(V)adsorption involved different interactions such as electrostatic attraction and surface complexation,while the adsorption of As(III)involved the part oxidization of As(III)to As(V)and the simultaneous adsorption of As(III)and As(V).In addition to the Ce(IV)in CeO_(2)·H_(2)O acted as an oxidant,the synergistic effect ofα-FeO(OH)and AgNPs also contributed to the oxidization of As(III)to As(V).Moreover,the reusable property suggested that this FeO(OH)-HCO-Ag-D201 nanocomposite has great potential for arsenic-contaminated water purification.
基金supported by the National Natural Science Foundation of China(Grant Nos.42277165,41920104007)the Hubei Natural Science Foundation(Grant No.2023AFD217).
文摘The safety of the initial support during the construction of inclined shafts in tunnels traversing through high-hydraulic-pressure surrounding rocks is paramount.This study examines a high-hydraulic-pressure inclined shaft of a tunnel in Western Sichuan Province to analyze the damage characteristics of the initial support and propose a radial drainage and decompression treatment method.Field monitoring was conducted to assess the load and deformation of the initial support structure,and on-site investigations identified the distribution of cracked areas.In addition,numerical simulations were performed to evaluate the force and deformation characteristics of the initial support structure,which were then compared with field observations for validation.The variations in the lateral pressure coefficient and water pressure were evaluated.The results revealed that damage was primarily concentrated in the shoulder,spring line,and knee areas,with the bending moment at the knee increasing by up to 66.9%.The application of the radial drainage and decompression treatment method effectively reduced water pressure loads on the initial support.Post-treatment analysis indicated significant reductions in axial force and bending moment,enhancing structural stability.These findings provide valuable insights for improving the safety and durability of initial support systems in inclined shafts of high-hydraulicpressure railroad tunnels.
基金supported by the National Natural Science Foundation of China(No.82360897)Natural Science Foundation of Jiangxi Province of China(No.20212BAB216007)Administration of Traditional Chinese Medicine of Jiangxi Province of China(No.2022A328).
文摘Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.
基金supported by the National Natural Science Foundation of China(Nos.22304027 and 81570807)the Natural Science Foundation of Fujian Province(No.2022J01208)+2 种基金the Joint Funds for the Innovation of Science and Technology,Fujian Province(Nos.2024Y9109,2024Y9107,and 2024Y9103)the Startup Fund for Scientific Research,Fujian Medical University(No.XRCZX2021015)the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases,and Xiang An Biomedicine Laboratory(No.2023XAKJ0101018).
文摘Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.
