数字普惠金融对农业高质量发展的作用机制——农村产业和农地流转的视角

数字普惠金融的普惠性、可达性和长尾性,对解决农业这一弱质性产业面临的金融排斥问题,进而促进农业高质量发展具有重要的作用。基于2011—2020年30个省份面板数据,实证分析数字普惠金融对我国农业高质量发展的作用机制。研究结果表明:数字普惠金融显著促进了我国农业的高质量发展,且对东部地区的影响大于中西部地区,对农业共享性发展的促进作用最明显,在支持农业绿色发展上的作用较弱;数字普惠金融通过加速农村产业融合、提高农地流转效率推动农业高质量发展;产业结构优化对农业高质量发展起到了正向调节作用。因此,我国应因地制宜施行数字普惠金融发展政策,促进数字普惠金融与绿色金融的融合;强化数字普惠金融加速产业融合和土地流转的功能;优化产业结构,为数字金融促进农业高质量发展提供条件;着重推动农业共享发展,为农业高质量发展增长赋能。

Electrocatalytic CO_(2) reduction to C_(2)H_(4): From lab to fab

The global concerns of energy crisis and climate change,primarily caused by carbon dioxide(CO_(2)),are of utmost importance.Recently,the electrocatalytic CO_(2) reduction reaction(CO_(2)RR) to high value-added multi-carbon(C_(2+)) products driven by renewable electricity has emerged as a highly promising solution to alleviate energy shortages and achieve carbon neutrality.Among these C_(2+) products,ethylene(C_(2)H_(4))holds particular importance in the petrochemical industry.Accordingly,this review aims to establish a connection between the fundamentals of electrocatalytic CO_(2) reduction reaction to ethylene(CO_(2)RRto-C_(2)H_(4)) in laboratory-scale research(lab) and its potential applications in industrial-level fabrication(fab).The review begins by summarizing the fundamental aspects,including the design strategies of high-performance Cu-based electrocatalysts and advanced electrolyzer devices.Subsequently,innovative and value-added techniques are presented to address the inherent challenges encountered during the implementations of CO_(2)RR-to-C_(2)H_(4) in industrial scenarios.Additionally,case studies of the technoeconomic analysis of the CO_(2)RR-to-C_(2)H_(4) process are discussed,taking into factors such as costeffectiveness,scalability,and market potential.The review concludes by outlining the perspectives and challenges associated with scaling up the CO_(2)RR-to-C_(2)H_(4) process.The insights presented in this review are expected to make a valuable contribution in advancing the CO_(2)RR-to-C_(2)H_(4) process from lab to fab.

Demonstration of safety characteristics and effects on gut microbiota of Lactobacillus gasseri HMV18

Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.

Aberrant expression of BDNF might serve as a candidate target for cocaine- induced psychosis: insights from bioinformatics analysis and microarray validation

Background Cocaine use disorder(CUD)and associated psychosis are major public health issues worldwide,along with high relapse outcome and limited treatment options.Exploring the molecular mechanisms underlying cocaine-induced psychosis(CIP)could supply integrated insights for understanding the pathogenic mechanism and potential novel therapeutic targets.Aims The aim of the study was to explore common alterations of CUD-schizophrenia target genes and identify core risk genes contributing to CIP through data mining and network pharmacology approach.Methods Target genes of CUD were obtained from GeneCards,Comparative Toxicogenomics Database,Swiss Target Prediction platform and PubChem.Schizophrenia-related target genes were derived from DisGeNET,GeneCards,MalaCards and Online Mendelian Inheritance in Man databases.Then,the overlap genes of these two sets were regarded as risk genes contributing to CIP.Based on these CUD-schizophrenia target genes,functional annotation and pathway analysis were performed using the clusterProfiler package in R.Protein-protein interaction network construction and module detection were performed based on the Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape software.Gene expression datasets GSE54839 and GSE93577 were applied for data validation and diagnostic capacity evaluation of interested hub genes.Results A total of 165 CUD-schizophrenia target genes were obtained.These genes were mainly contributing to chemical synaptic transmission,neuropeptide hormone activity,postsynaptic membrane and neuroactive ligand-receptor interaction pathway.Network analysis and validation analysis indicated that BDNF might serve as an important risk gene in mediating CIP.Conclusions This study generates a holistic view of CIP and provides a basis for the identification of potential CUD-schizophrenia target genes involved in the development of CIP.The abnormal expression of BDNF would be a candidate therapeutic target underlying the pathogenesis of CUD and associated CIP.

Strategies and methods for fabricating high quality metal halide perovskite thin films for solar cells

With the development of human society,the problems of environmental deterioration and energy shortage have become increasingly prominent.In order to solve these problems,metal halide perovskite solar cells(PSCs)stand out because of their excellent properties(i.e.,high optical absorption coefficient,long carrier lifetime and carrier diffusion length,adjustable band gap)and have been widely studied.PSCs with low cost,high power conversion efficiency and high stability are the future development trend.The quality of perovskite film is essential for fabricating PSCs with high performance.To provide a full picture of realizing high performance PSCs,this review focuses on the strategies for preparing high quality perovskite films(including antisolvent,Lewis acid-base,additive engineering,scaleable fabrication,strain engineering and band gap adjustment),and therefore to fabricate high performance PSCs and to accelerate the commercialization.

Experiment on acoustic emission response and damage evolution characteristics of polymer-modified cemented paste backfill under uniaxial compression

The mechanical properties of cemented paste backfill(CPB)determine its control effect on the goaf roof.In this study,the mechanical strength of polymer-modified cemented paste backfill(PCPB)samples was tested by uniaxial compression tests,and the failure characteristics of PCPB under the compression were analyzed.Besides,acoustic emission(AE)technology was used to monitor and record the cracking process of the PCPB sample with a curing age of 28 d,and two AE indexes(rise angle and average frequency)were used to classify the failure modes of samples under different loading processes.The results show that waterborne epoxy resin can significantly enhance the mechanical strength of PCPB samples(when the mass ratio of polymer to powder material is 0.30,the strength of PCPB samples with a curing age of 28 d is increased by 102.6%);with the increase of polymer content,the mechanical strength of PCPB samples is improved significantly in the early and middle period of curing.Under uniaxial load,the macro cracks of PCPB samples are mostly generated along the axial direction,the main crack runs through the sample,and a large number of small cracks are distributed around the main crack.The AE response of PCPB samples during the whole loading process can be divided into four periods:quiet period,slow growth period,rapid growth period,and remission period,corresponding to the micro-pore compaction stage,elastic deformation stage,plastic deformation stage,and failure instability stage of the stress-strain curve.The AE events are mainly concentrated in the plastic deformation stage;both shear failure and tensile failure occur in the above four stages,while tensile failure is dominant for PCPB samples.This study provides a reference for the safety of coal pillar recovery in pillar goaf.

Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Characteristics of Patients Sponsored by the Internet Platforms of Medical Mutual Aid

The morbidity and mortality of life-threatening diseases such as cancers are increasing year by year in China. Although the national medical insurance has been improved a lot, it still falls short of expecting “universal medical insurance”. To help the families of patients with cancer and other serious diseases to resolve the unaffordable medical cost, several internet platforms of “Peer to Peer Medical Mutual Aid” have gradually emerged recently. In the form of low threshold insurance combined with public support, these platforms provide subsidies to families of patients suffering from serious financial burden and then partly compensate them for the limit of national medical insurance. This article summarized the characteristics of declared patients sponsored by several medical mutual aid internet platforms. The results showed that the sponsored patients were mostly cancer patients (90.1%), aged 21 - 60 (88.4%), and the average amounts of financial support had a trend to decrease with the increase of age. In particular, the reported cases of thyroid cancer were increased dramatically recently, however, with a lowest average mutual aid fund. Given these data, it is urgent to list out a detailed rule for the use of national medical insurance on the treatment of cancer, to heighten the healthcare system for the occupational population, age from 21 to 60, and to establish the credit system for Medicare and Medicaid services.

分殊偏待与家族企业竞争优势:一个理论框架

在家族企业内部,控股家族通常会针对家族成员和非家族成员进行区别对待,并给予家族成员更好的待遇,从而出现“分殊偏待”这一家族企业独特现象。“分殊偏待”在中国家族企业中普遍存在,且对企业的战略选择和竞争优势具有重要影响。本文对目前关于分殊偏待的研究成果进行梳理与整合,从分殊偏待的概念内涵与表现形式入手,辨析分殊偏待与其他领导差别对待概念之间的区别,从不同角度梳理分殊偏待的产生原因。结合企业竞争优势的文献成果,以资源基础观的VRIO框架作为理论基础,深入剖析分殊偏待与家族企业竞争优势之间的作用机制及其边界条件,在文献综述与理论推演的基础上提出若干命题,构建了一个综合性的理论分析框架,并为未来分殊偏待的研究提供思路与方向。

Hetero‑Interfaces on Cu Electrode for Enhanced Electrochemical Conversion of CO_(2)to Multi‑Carbon Products

Electrochemical CO_(2)reduction reaction(CO_(2)RR)to multi-carbon products would simultaneously reduce CO_(2)emission and produce high-value chemicals.Herein,we report Cu electrodes modified by metal–organic framework(MOF)exhibiting enhanced electrocatalytic performance to convert CO_(2) into ethylene and ethanol.The Zr-based MOF,UiO-66 would in situ transform into amorphous ZrOx nanoparticles(a-ZrO_(x)),constructing a-ZrOx/Cu hetero-interface as a dual-site catalyst.The Faradaic efficiency of multi-carbon(C2+)products for optimal UiO-66-coated Cu(0.5-UiO/Cu)electrode reaches a high value of 74%at−1.05 V versus RHE.The intrinsic activity for C2+products on 0.5-UiO/Cu electrode is about two times higher than that of Cu foil.In situ surface-enhanced Raman spectra demonstrate that UiO-66-derived a-ZrO_(x)coating can promote the stabilization of atop-bound CO^(*)intermediates on Cu surface during CO_(2)electrolysis,leading to increased CO^(*)coverage and facilitating the C–C coupling process.The present study gives new insights into tailoring the adsorption configurations of CO_(2)RR intermediate by designing dual-site electrocatalysts with hetero-interfaces.

Numerical investigation on electron effects in the mass transfer of the plasma species in aqueous solution

The objective of this work is to contribute an understanding of the effects of electrons in the plasmas on the mass transfer of plasma species in aqueous solution by means of the numerical simulation based on a one-dimensional diffusion-reaction model.The plasma species are divided into two groups,i.e.electrons and the other species,and the mass transfer in the three scenarios has been simulated,including the systematic calculations of the depth distributions of five major reactive species,OH,O3,HO2,O2^-,and H2O2.In the three scenarios,the particles considered to enter into aqueous solution are all the plasma species(the scenario Ⅰ,where the mass transfer of plasma species is a result due to the synergy of the electrons and the other plasma species),the other species(the scenario Ⅱ),and only electrons in plasma species(the scenario Ⅲ),respectively.The detailed analyses on the difference between the depth distributions of each reactive species in these three scenarios show the following conclusions.The electrons play an important role in the mass transfer of plasma species in aqueous solution and the synergy of the electrons and the other plasma species(the electron-species synergy)presents its different effects on the mass transfer.The vast majority of H2O2 are generated from a series of the electronrelated reactions in aqueous solution,which is hardly affected by the electron-species synergy.Compared to the results when only the electrons enter into the liquid region,the electron-species synergy evidently weakens the generation of O2^-,O3,and OH,but promotes to produce HO2.

Metal phenolic network-stabilized nanocrystals of andrographolide to alleviate macrophage-mediated inflammation in-vitro

Macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential targets for treating inflammatory diseases.Andrographolide(AND)is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB/MAPK pathway in activated macrophages.Although AND has many medicinal properties,its lower water solubility and first-pass effect in the liver have hindered its clinical application.In this context,by using a metal phenolic network as a stabilizer,we designed and prepared highly stabilized AND nanocrystals(AND-MPN Ns)with high drug loading capacity to facilitate the clinical application of AND.Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization,reducing proinflammatory cytokines IL-6 and TNF-α,and suppressing the NF-κB signaling pathway activation.The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.

Liposomal codelivery of inflammation inhibitor and collagen protector to the plaque for effective anti-atherosclerosis

Plaque plays a central role in atherosclerosis(AS)progression,whereas inflammation and destruction of the plaque microenvironment contribute to plaque advancement.As a result,a therapy regime,which combines anti-inflammation and inhibition-degradation of plaque matrix,appears to be a promising strategy to combat AS.Herein,we report a p H-sensitive liposome co-loading with the anti-inflammatory agent(oridonin,ORD)and plaque-collagen protector(marimastat)for anti-AS therapy.ORD was first conjugated with hyaluronic acid(HA)to target the inflammation contributor,pro-inflammatory macrophages.Then,the conjugate assembled onto the MATT-loaded liposomes.The co-loaded system(150 nm)significantly improved pharmacokinetics over the liposomes without anchoring the conjugate and accumulated effectively in the plaque.The preparation administration allowed efficient anti-AS activities in high-fat diet(HFD)-Apoe-/-mice by decreasing the pro-inflammatory cytokine expression in the serum,lessening the lesion area,alleviating the plaque collagen degradation,promoting macrophage polarization from phenotypic M1 to M2,reducing T helper(Th)17 cells(Th17)/T regulatory cells(Tregs)and Th1/Th2 ratio,etc.Furthermore,the serum determination in AS patients demonstrated high expression of the inflammatory cytokines,indicating our finding may offer a potential guideline for clinical practice.

Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy,despite considerable success in anti-tumor immunotherapy.The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy.We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response.Herein,a targeted diterpenoid derivative was integrated with the checkpoint blockade(anti-CTLA-4)to improve immunotherapy using thermo sensitive liposomes as carriers.In vivo,the liposomes enabled the co-delivery of the two drug payloads into the tumor.Consequently,the regulatory T cell proliferation was restrained,the cytotoxic T cell infiltration was enhanced,and the profound immunotherapeutic effect was achieved.In addition,the immunotherapeutic effect of another clinically used checkpoint antibody,anti-PD-1,also benefited from the diterpenoid derivative.Of note,our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction.Collectively,co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy.We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Surface Dielectric Barrier Discharge

This project is concerned with surface dielectric barrier discharge(DBD),which involve designing the configuration of discharge and experiment,collecting and analysis data from experiment and simulation.Therefore,this report includes the objective of the project and general information of background.It also briefly introduces the history and theory of dielectric barrier discharge.For the experiment how to design the discharge implement and why.Then it will show the experiment in different configurations,and the analysis data collected in experiment also explain the data for finding out the properties of surface dielectric barrier discharge and what the difference between surface discharge and vertical discharge are.High frequency power supplied will be used for viewing the phenomenon of discharge.Compare the spectrums of discharge on dielectric and air discharge.Finally,it is the main conclusions and introduction of the difference of surface dielectric barrier discharge and vertical discharge.There are some conclusions.Discharge voltage increase linearly with applied voltage.Discharge power increase non-linearly with the discharge voltage.The gap of high voltage electrodes will not affect discharge voltage and discharge power.Discharge power increases with the frequency of power supply.Discharge area will expand when the applied voltage increases.

Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation

Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vector”of rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial cells.The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%SOD.Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine model.Particularly,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect.In vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial cells.In vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the lungs.In conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation.The study offers a promising approach to combat pulmonary endothelium-associated diseases.

Convergence and Stability of an Explicit Method for Autonomous Time-Changed Stochastic Differential Equations with Super-Linear Coefficients

In this paper,numerical methods for the time-changed stochastic differential equations of the form dY(t)=a(Y(t))dt+b(Y(t))dE(t)+s(Y(t))dB(E(t))are investigated,where all the coefficients a(·),b(·)and s(·)are allowed to contain some super-linearly growing terms.An explicit method is proposed by using the idea of truncating terms that grow too fast.Strong convergence in the finite time of the proposed method is proved and the convergence rate is obtained.The proposed method is also proved to be able to reproduce the asymptotic stability of the underlying equation in the almost sure sense.Simulations are provided to demonstrate the theoretical results.

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through b-catenin/CREB interruption

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments.In this work,a transferrin receptor(TfR)targeted immunostimulant(PTI)is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting b-catenin signal pathway.To synthesize PTI,the photosensitizer conjugated TfR targeting peptide moiety(Palmitic-K(PpIX)-HAIYPRH)is unitized to encapsulate the transcription interrupter of ICG-001.On the one hand,the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumorassociated antigens.On the other hand,PTI will interrupt the binding between b-catenin andcAMP response element-binding protein(CREB),regulating the gene transcription to downregulate programmed death ligand 1(PD-L1)while upregulating CeC motif chemokine ligand 4(CCL4).Furthermore,the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration,and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis.This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

The response and anti-stress mechanisms of nitrifying sludge under long-term exposure to Cd Se quantum dots

The wide application of CdSe quantum dots(QDs)increases its stress risk to sewage treatment systems.This study evaluated the response of nitrification performance,floc characteristics and microbial community of nitrifying sludge under long-term exposure to CdSe QDs.Results showed CdSe QDs(≥1 mg/L)would decrease the activity of ammonia monooxygenase(AMO).Under the stress of 30 mg/L CdSe QDs,the activity of AMO was reduced by 66%,while the activities of hydroxylamine oxidase and nitrite oxidoreductase were enhanced by 19.1%and 26%,respectively.Thus,the final nitrification effects were not adversely affected,and the production rates of NO_(2)^(-)-N and NO_(3)^(-)-N were accelerated.Additionally,CdSe QDs improved biomass concentration in sludge and maintained the stability of sludge settleability.High throughput sequencing analysis showed that CdSe QDs evidently reduced the abundance and diversity of microbial community in nitrifying sludge.The abundances of amino acid metabolism and lipid metabolism were enriched.Moreover,CdSe QDs decreased the fluorescence intensity of tryptophan-like protein from 2,326 to 1,179 a.u.in loosely bound extracellular polymeric substances(EPSs)and from 3,792 to 3,117 a.u.in tightly bound EPSs.To relieve CdSe QD stress,the polysaccharide content increased from0.31 to 0.61 mg/g MLSS and intracellular antioxidant defense was activated.With CdSe QD level increasing to 30 mg/L,the total antioxygenic capacity and the activities of catalase were enhanced up to 411%and 143.2%,respectively.Thereby,CdSe QDs had little adverse effects on cell membrane integrity,microbial metabolism and the abundance of Nitrospirae.

Multifunctional nanoparticle-mediated combining therapy for human diseases

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.