The accurate prediction of drug absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties represents a crucial step in early drug development for reducing failure risk.Current deep learning approaches...The accurate prediction of drug absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties represents a crucial step in early drug development for reducing failure risk.Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks.This research proposes molecular properties prediction with parallel-view and collaborative learning(MolP-PC),a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints(MFs),2D molecular graphs,and 3D geometric representations,incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions.Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks,with its multi-task learning(MTL)mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks.Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization.A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC’s effective generalization in predicting key pharmacokinetic parameters such as half-life(T0.5)and clearance(CL),indicating its practical utility in drug modeling.However,the model exhibits a tendency to underestimate volume of distribution(VD),indicating potential for improvement in analyzing compounds with high tissue distribution.This study presents an efficient and interpretable approach for ADMET property prediction,establishing a novel framework for molecular optimization and risk assessment in drug development.展开更多
Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,w...Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,we introduced a novel nanotherapeutic approach involving a curcumin-loaded ceria nanoenzyme delivery system tailored to counteract the multifaceted aspects of ALI.This system leverages the individual and combined effects of the components to provide a comprehensive therapeutic solution.The dual-action capability of this nanosystem was manifested by mitigating mitochondrial oxidative stress in lung epithelial cells and inhibiting the transient receptor potential melanosome-associated protein 2(TRPM2)-NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,offering a highly effective therapeutic approach to ALI.Our findings reveal the underlying mechanisms of this innovative nanodelivery system,showcasing its potential as a versatile strategy for ALI treatment and encouraging further exploration of nanoenzyme-based therapies for ALI.展开更多
Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkl...Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkle of films on non-linear elastic substrates has received less attention.In this article,a unique wrinkle evolution of the film-substrate system with a J-shaped non-linear stress-strain relation is reported.The result shows that a concave hexagonal array pattern is formed with the shrinkage strain of the film-substrate systems developing.As the interconnection of hexagonal arrays,a unit cell ridge network appears with properties such as chirality and helix.The subparagraph maze pattern formed with high compression is mainly composed of special single-cell ridge networks such as spiral single cores,chiral double cores,and combined multi-cores.This evolutionary model is highly consistent with the results of experiments,and it also predicts wrinkle morphology that has not yet been reported.These findings can serve as a novel explanation for the surface wrinkle of biological soft tissue,as well as provide references for the preparation of artificial biomaterials and programmable soft matter.展开更多
Objective: The partial inferior turbinectomy and septoplasty was applied to treat the allergic perennial rhinitis (APR), and to observe the ultrastructure changes of the nasal mucosa before and after the operations. M...Objective: The partial inferior turbinectomy and septoplasty was applied to treat the allergic perennial rhinitis (APR), and to observe the ultrastructure changes of the nasal mucosa before and after the operations. Methods: For 36 cases of research objects diagnosed with APR, the partial inferior turbinectomy and septoplasty was administered. For 6 APR cases among them, the pre- and postoperative observation of anterior nasal mucosa of the inferior turbinate on the same side under the electron microscope was conducted for one year respectively. In addition, their pathological alterations of tissues were also conducted. Results: In the pre-operative observation under the electron microscope, it was found that the nasal mucosae epithelium cells were nude without cilia. The lamina propria had edema, and mesenchyme presented the infiltration of substantial eosinophilic granulocytes, basophilic granulocytes, plasmacytes and mast cells. Additionally, abundant degranulation and vacuolation of cytoplasts were observed. The plentiful glands, duct ectasia, edema and structural changes were also found. Some gland cells had degenerated. After the operation, it was found that the epithelium nudity still existed and the deficiency of cilia was not improved. Only a very small amount of microvilli existed. The edema of lamina propria was improved and eosinophilic granulocytes were rarely observed in mesenchyme. However, the infiltration of basophilic granulocytes, plasmocytes and mast cells was still observed. The particle structure was generally stable and the central crystal was clear without degranulation. Meanwhile, the amount of glands was reduced and the tissue structure tended to be recovered. Overall, the nasal mucosa showed changes as chronic inflammation. Conclusions: For the treatment of APR with the methods presented by our research institution, in one year before and after the operation, ultrastructural changes of inferior turbinate mucosa tissues were observed from the preoperatively pathological changes of typical APR to the chronic inflammation with the primary infiltration of neutrophilic granulocyte and mast cells.展开更多
Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia....Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.展开更多
OBJECTIVE: To examine whether electroacupuncture(EA) treatment inhibited cell apoptosis of intervertebral annulus fibrosis(AF) via tumor necrosis factor-α(TNF-α)-tumor necrosis factor receptor 1(TNFR1)-caspase-8 and...OBJECTIVE: To examine whether electroacupuncture(EA) treatment inhibited cell apoptosis of intervertebral annulus fibrosis(AF) via tumor necrosis factor-α(TNF-α)-tumor necrosis factor receptor 1(TNFR1)-caspase-8 and integrin β1/Akt signaling pathways in a rat model of cervical intervertebral disc degeneration caused by unbalanced dynamic and static forces.METHODS: Thirty-two Sprague-Dawley rats were included in this study, of which 24 rats underwent surgery to induce cervical intervertebral disc degeneration, while eight rats received EA treatment at Dazhui(GV 14). Immunohistochemical staining was used to detect TNF-α, TNFR1, and caspase-8Apoptosis of AF cells was examined with terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling(TUNEL) staining. The m RNA and protein expression levels of integrin β1 andAkt were evaluated with real-time polymerase chain reaction and western blot analysis, respectively.RESULTS: Treatment with EA decreased TUNEL-positive AF cells and lowered TNF-α, TNFR1 and caspase-8 positive cells compared with control groups. EA treatment also increased integrin β1and Akt m RNA and protein levels compared with controls.CONCLUSION: Treatment with EA inhibits AF cell apoptosis through suppression of the TNF-α-TNFR1-caspase-8 signal pathway and increases the expression of integrin β1 and Akt. EA may be a good alternative therapy for treating cervical spondylosis.展开更多
Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions.As reproductive organs,unisexual flowers have different reproductiv...Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions.As reproductive organs,unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism.To date,little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers.We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination(the early,blooming and late stages)via transcriptional sequencing as well as metabolite content and phenotypic analysis.We found that a large number of sex-biased genes,rather than sex-limited genes,were responsible for sexual dimorphism in S.paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development.The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages.Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes.These sex-biased genes were involved mainly in signal transduction,photosynthesis,respiration,cell proliferation,phytochrome biosynthesis,and phenol metabolism;therefore,they resulted in more biomass accumulation and higher energy consumption in male catkins.Our results indicated that sex-biased gene expression in S.paraplesia flowers is associated with different reproductive investments in unisexual flowers;male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.展开更多
Phosphorylated di-,tri-and tetra-saccharides ofβ-1,2-mannan antigen derived from Candida albicans(C.albicans)cell wall were synthesized and covalently conjugated with keyhole limpet hemocyanin(KLH)and human serum alb...Phosphorylated di-,tri-and tetra-saccharides ofβ-1,2-mannan antigen derived from Candida albicans(C.albicans)cell wall were synthesized and covalently conjugated with keyhole limpet hemocyanin(KLH)and human serum albumin(HSA)via a bifunctional linker under mild conditions.The semi-syntheticβ-1,2-mannoside–KLH conjugates were evaluated for the immunization of BALB/c mice.The ELISA results revealed that all three conjugates could elicit high levels of specific IgG antibodies and the acquired antisera could effectively identify theβ-1,2-mannan epitope.Furthermore,the immunofluorescence and flow cytometry assays also uncovered that the induced antibodies,especially that obtained from immunization withβ-1,2-mannotriose–KLH conjugate(1b),could bind well to fungi cell.Eventually,the structure–immunogenicity relationship analysis ofβ-mannan showed that the length of oligo-β-mannoses had a big impact on their immunogenicity andβ-1,2-mannotriose showed the strongest immunogenicity.The results suggested the great potential ofβ-1,2-mannotriose–KLH conjugate as an antifungal vaccine candidate.展开更多
Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated wit...Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.展开更多
Doping is an effective approach for improving the photovoltaic performance of Cu2 ZnSnS4（CZTS）. The doping by substitution of Cu atoms in CZTS with Li and Ag atoms is investigated using density functional theory. Th...Doping is an effective approach for improving the photovoltaic performance of Cu2 ZnSnS4（CZTS）. The doping by substitution of Cu atoms in CZTS with Li and Ag atoms is investigated using density functional theory. The results show that the band gaps of Li（2 x）Cu2（1-x）ZnSnS4 and Ag（2 x）Cu2（1-x）ZnSnS4 can be tuned in the ranges of 1.30-3.43 and 1.30-1.63 eV, respectively. The calculation also reveals a phase transition from kesterite to wurtzite-kesterite for Li（2 x）Cu2（1-x）ZnSnS4 as x is larger than 0.9. The tunable band gaps of Li（2 x）Cu2（1-x）ZnSnS4 and Ag（2 x）Cu2（1-x） ZnSnS4 make them beneficial for achieving band-gap-graded solar cells.展开更多
BACKGROUND Although acute graft-vs-host disease(aGvHD)is a rare complication of liver transplantation,it is poorly understood and has an extremely high mortality rate.No standardized diagnostic criteria or treatment r...BACKGROUND Although acute graft-vs-host disease(aGvHD)is a rare complication of liver transplantation,it is poorly understood and has an extremely high mortality rate.No standardized diagnostic criteria or treatment regimens currently exist.CASE SUMMARY The present study investigated the etiology,diagnosis,and treatment of aGvHD following liver transplantation.Presentation,diagnosis,disease course,histology,and treatment of an aGvHD case are reported,and associated literature is reviewed.A 64-year-old female required LTx due to primary biliary cirrhosis.The donor was a 12-year-old male.Three weeks following liver transplantation,the recipient developed pyrexia,diarrhea,rashes,and antibiotic-unresponsive pancytopenia.Clinical symptoms together with laboratory investigations suggested a diagnosis of aGvHD,which was confirmed via peripheral blood fluorescent in situ hybridization.Donor XY chromosome fluorescent in situ hybridization indicating early chimerism achieved 93%sensitivity in the detection of GvHD.Existing immunosuppressants were discontinued,and high-dose intravenous methylprednisolone was initiated along with antibiotics.While diarrhea resolved,the patient’s general condition continued to deteriorate until demise due to multi-system organ failure at 37 d post-liver transplantation.This case illustrates the life-threatening nature of aGvHD.CONCLUSION Herein,we have summarized a post-LTx aGvHD case and reviewed associated literature in order to increase awareness and provide potentially risk-mitigating recommendations.展开更多
The culture of professional degree graduate students is a new form of postgraduate education in China. It focuses on cultivating high-level and applied talents compared with original academic degree graduate students....The culture of professional degree graduate students is a new form of postgraduate education in China. It focuses on cultivating high-level and applied talents compared with original academic degree graduate students. Considering about the source of full-time professional degree graduate students in domain of software engineering and the current college educational system, this paper makes a few beneficial explorations about curriculum, practice teaching, process management and puts forward the mode and method to improve full-time professional degree graduate education in domain of Software Engineering.展开更多
Objective: To observe the changes on skin wheal and erythema of skin prick test for the patients with allergic rhinitis during SLIT. Methods: Since March 2010 the 103 cases of SLIT attacked by allergic rhinitis patien...Objective: To observe the changes on skin wheal and erythema of skin prick test for the patients with allergic rhinitis during SLIT. Methods: Since March 2010 the 103 cases of SLIT attacked by allergic rhinitis patients, divided into four age groups, respectively measured the diameter of skin wheal and erythema before treatment, six months, one year and 2 years after SLIT. The data were analyzed by analysis of variance method;P Results: The results showed that the most changes of skin erythema diameter were statistically significant in N1, N2, N3 age group during test observation compare with the data before SLIT (p Conclusion: Although most of the skin test wheal did not change significantly during the treatment of SLIT, the erythema reaction decreased to a certain extent, indicating that the intensity of histamine release may be reduced during the treatment.展开更多
The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β...The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β‐lactamase(NDM‐CRE),are prevalent in livestock and have acquired resistance to nearly all commonly used β‐lactam antibiotics.This study evaluated the efficacy of the antimicrobial peptide BMAP‐27B,a derivative of the cathelicidin family,against NDM‐CRE strains in food animals.BMAP‐27B showed potent antibacterial activity and rapid bactericidal effects against CRE,as well as comparable effects against human carbapenem‐resistant Acinetobacter baumannii.Furthermore,BMAP‐27B effectively penetrated and cleared biofilms formed by virulent strains of Escherichia coli and Klebsiella pneumoniae.Mechanistic studies indicated that BMAP‐27B exerts its antibacterial activity by disrupting bacterial membranes and inhibiting bacterial energy metabolism.BMAP‐27B effectively enhances the efficacy of carbapenems against NDM‐positive isolates by inhibiting efflux pump activity and chelating Zn^(2+) to inhibit NDM proteases,thus reversing carbapenem resistance in NDM‐CRE.Importantly,BMAP‐27B maintained excellent antimicrobial stability under extreme pH changes and high salt concentrations,along with resistance to serum and protease degradation.Investigations revealed that BMAP‐27B also shows ideal biocompatibility and therapeutic efficacy in vivo.In summary,the highly potent antibacterial activity of BMAP‐27B,along with its potential role as a broadspectrum antibiotic adjuvant,makes it a promising candidate for combating infections caused by foodborne NDM‐CRE and preventing pathogen transmission at the animal‐human‐environment interface.展开更多
The emergence of novel viral pathogens and the limitations of conventional antiviral therapies necessitate innovative strategies to combat persistent and pandemic threats.This review details the role of viral infectio...The emergence of novel viral pathogens and the limitations of conventional antiviral therapies necessitate innovative strategies to combat persistent and pandemic threats.This review details the role of viral infections and antiviral nanomedicines,delving into the mechanisms of action and antiviral advantages of nanomedicines,as well as the latest research advances in this field.The review systematically categorizes the mechanisms of antiviral nanodrugs into a framework that integrates previously fragmented knowledge,and innovatively summarizes the unique attributes and advantages of antiviral nanodrugs compared to small-molecule drugs.Nanotherapies are proposed in this review to conclude advanced nanoantivirals(e.g.,light-activated nano-photosensitizers,biomimetic decoys,PROTAC-based degraders,and gene-silencing platforms)and offer a distinctive narrative perspective,with the aim of presenting a merged and integrated overview of nanodrugs.By intuitively highlighting their commonalities in mechanisms or similarities in application methods,readers may better appreciate the innovative characteristics of different antivirals.We further discuss translational challenges and propose interdisciplinary solutions and future directions to accelerate the development of next-generation antiviral strategies.This review aims to inspire transformative research at the nexus of virology,nanotech-nology,and precision medicine.展开更多
Background:Phenotypic transition is a common resistance mechanism of targeted therapy.While transformations from lung adenocarcinoma(LUAD)to small-cell lung cancer or squamous-cell carcinoma have been extensively stud...Background:Phenotypic transition is a common resistance mechanism of targeted therapy.While transformations from lung adenocarcinoma(LUAD)to small-cell lung cancer or squamous-cell carcinoma have been extensively studied,the conversion into sarcomatoid carcinoma(SC)is rarely reported.Methods:Genetic and histological examinations were systematically performed on tumor re-biopsy samples ob-tained from patients with advanced EGFR-mutant LUAD who progressed on EGFR-tyrosine kinase inhibitors(TKIs).EGFR wild-type patients were also identified who underwent the rare transformation from adenocarci-noma to SC following the ineffectiveness of inhibitors that target distinct driver oncogenes.Furthermore,we also retrospectively collected 42 cases diagnosed with primary pulmonary SC as a comparison cohort to comprehen-sively characterize the biological events and clinical outcomes of transformed SC.Results:The sarcomatoid transformation mediated drug resistance in 2.5%and 4.8%of patients after failure on the first/second,and third-generation EGFR-TKIs.Transformation of sarcomatoid carcinoma is characterized by a higher frequency of TP53,RB1,and MET genetic alterations compared to cases lacking histological transforma-tion;the PI3K signaling pathway was also significantly activated.Fifteen individuals were identified with a rare transition from adenocarcinoma to SC,consisting of seven cases with EGFR-activating mutations and eight cases without EGFR mutations.All sarcomatoid-transformed samples not only retained their original driver mutations but also shared specific genetic alterations with primary LUAD.Moreover,transformed sarcomatoid carcinomas mimic the primary SC in terms of immunochemical and molecular features.Conclusions:The transformation from lung adenocarcinoma to SC is a resistance mechanism wildly applied to inhibitors targeting different driver oncogenes.Immunotherapy plus chemotherapy shows potential to benefit patients with sarcomatoid transformation and warrants further study in larger cohorts.展开更多
Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammat...Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.展开更多
本文研究广义部分线性单指标模型(generalized partially linear single-index models,GPLSIMs)的模型平均问题.在实际应用中,GPLSIMs由于其灵活性和易解释性受到广泛关注.然而,GPLSIMs在应用中存在两类不确定性:变量的不确定性和单指...本文研究广义部分线性单指标模型(generalized partially linear single-index models,GPLSIMs)的模型平均问题.在实际应用中,GPLSIMs由于其灵活性和易解释性受到广泛关注.然而,GPLSIMs在应用中存在两类不确定性:变量的不确定性和单指标连接函数光滑度的不确定性.为了解决该不确定性问题,本文提出一种GPLSIMs的最优模型平均方法,该方法通过最大交叉验证准则得到数据驱动的权重.在模型误设定假设和发散模型空间的框架下,本文证明在最小化Kullback-Leibler(KL)损失准则下,所提出的模型平均估计渐近最优.同时,当候选模型集中存在伪真模型时,本文证明基于交叉验证准则得到的权重渐近地集中在伪真模型上.此外,基于提出的模型平均方法,本文为GPLSIMs构建了一种变量重要性度量,并证明该度量可以渐近识别所有真实模型中的变量.模拟研究和两个实际数据分析均展示了本文提出的方法相对于几种现有方法的优势.展开更多
基金supported by the research on key technologies for monitoring and identifying drug abuse of anesthetic drugs and psychotropic drugs,and intervention for addiction(No.2023YFC3304200)the program of a study on the diagnosis of addiction to synthetic cannabinoids and methods of assessing the risk of abuse(No.2022YFC3300905)+1 种基金the program of Ab initio design and generation of AI models for small molecule ligands based on target structures(No.2022PE0AC03)ZHIJIANG LAB.
文摘The accurate prediction of drug absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties represents a crucial step in early drug development for reducing failure risk.Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks.This research proposes molecular properties prediction with parallel-view and collaborative learning(MolP-PC),a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints(MFs),2D molecular graphs,and 3D geometric representations,incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions.Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks,with its multi-task learning(MTL)mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks.Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization.A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC’s effective generalization in predicting key pharmacokinetic parameters such as half-life(T0.5)and clearance(CL),indicating its practical utility in drug modeling.However,the model exhibits a tendency to underestimate volume of distribution(VD),indicating potential for improvement in analyzing compounds with high tissue distribution.This study presents an efficient and interpretable approach for ADMET property prediction,establishing a novel framework for molecular optimization and risk assessment in drug development.
基金funded by the National Natural Science Foundation of China(Nos.82103885,81871521,82273672)Natural Science Foundation of Shanghai(Nos.21ZR1477700,20ZR1470300)+1 种基金the Shanghai Municipal Health Commission-Outstanding Youth Foundation of Public Health(No.GWV-10.2-YQ48)Sci Tech Funding by CSPFTZ Lingang Special Area Marine Biomedical Innovation Platform。
文摘Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,we introduced a novel nanotherapeutic approach involving a curcumin-loaded ceria nanoenzyme delivery system tailored to counteract the multifaceted aspects of ALI.This system leverages the individual and combined effects of the components to provide a comprehensive therapeutic solution.The dual-action capability of this nanosystem was manifested by mitigating mitochondrial oxidative stress in lung epithelial cells and inhibiting the transient receptor potential melanosome-associated protein 2(TRPM2)-NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,offering a highly effective therapeutic approach to ALI.Our findings reveal the underlying mechanisms of this innovative nanodelivery system,showcasing its potential as a versatile strategy for ALI treatment and encouraging further exploration of nanoenzyme-based therapies for ALI.
基金This work was supported by the Youth Project of Hunan Provincial Department of Education(Grant No.22B0334)the Bridge and Tunnel Engineering Innovation Project of Changsha University of Science&Technology(Grant No.11ZDXK11)and the Practical Innovation and Entrepreneurship Capacity Improvement Plan of Changsha University of Science and Technology(Grant No.CLSJCX23029).
文摘Organisms have evolved a strain limiting mechanism,reflected as a non-linear elastic constitutive,to prevent large deformations from threatening soft tissue integrity.Compared with linear elastic substrates,the wrinkle of films on non-linear elastic substrates has received less attention.In this article,a unique wrinkle evolution of the film-substrate system with a J-shaped non-linear stress-strain relation is reported.The result shows that a concave hexagonal array pattern is formed with the shrinkage strain of the film-substrate systems developing.As the interconnection of hexagonal arrays,a unit cell ridge network appears with properties such as chirality and helix.The subparagraph maze pattern formed with high compression is mainly composed of special single-cell ridge networks such as spiral single cores,chiral double cores,and combined multi-cores.This evolutionary model is highly consistent with the results of experiments,and it also predicts wrinkle morphology that has not yet been reported.These findings can serve as a novel explanation for the surface wrinkle of biological soft tissue,as well as provide references for the preparation of artificial biomaterials and programmable soft matter.
文摘Objective: The partial inferior turbinectomy and septoplasty was applied to treat the allergic perennial rhinitis (APR), and to observe the ultrastructure changes of the nasal mucosa before and after the operations. Methods: For 36 cases of research objects diagnosed with APR, the partial inferior turbinectomy and septoplasty was administered. For 6 APR cases among them, the pre- and postoperative observation of anterior nasal mucosa of the inferior turbinate on the same side under the electron microscope was conducted for one year respectively. In addition, their pathological alterations of tissues were also conducted. Results: In the pre-operative observation under the electron microscope, it was found that the nasal mucosae epithelium cells were nude without cilia. The lamina propria had edema, and mesenchyme presented the infiltration of substantial eosinophilic granulocytes, basophilic granulocytes, plasmacytes and mast cells. Additionally, abundant degranulation and vacuolation of cytoplasts were observed. The plentiful glands, duct ectasia, edema and structural changes were also found. Some gland cells had degenerated. After the operation, it was found that the epithelium nudity still existed and the deficiency of cilia was not improved. Only a very small amount of microvilli existed. The edema of lamina propria was improved and eosinophilic granulocytes were rarely observed in mesenchyme. However, the infiltration of basophilic granulocytes, plasmocytes and mast cells was still observed. The particle structure was generally stable and the central crystal was clear without degranulation. Meanwhile, the amount of glands was reduced and the tissue structure tended to be recovered. Overall, the nasal mucosa showed changes as chronic inflammation. Conclusions: For the treatment of APR with the methods presented by our research institution, in one year before and after the operation, ultrastructural changes of inferior turbinate mucosa tissues were observed from the preoperatively pathological changes of typical APR to the chronic inflammation with the primary infiltration of neutrophilic granulocyte and mast cells.
基金supported by the National Natural Science Foundation of China(No.81774033 and No.81773736)the Hunan Provincial Department of Education-funded Scientific Research Project(No.18C0379 and No.19A378)。
文摘Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways.
基金the National Natural Science Foundation of China(No.81273836,Based on Ineegrin/FAK signaling pathways research the effects of electroacupuncture on the contents of apoptosisNo.81001554,Based on Wnt/β-catenin signaling pathways research the effects of electroacupuncture on the annulus fibrosis cells)
文摘OBJECTIVE: To examine whether electroacupuncture(EA) treatment inhibited cell apoptosis of intervertebral annulus fibrosis(AF) via tumor necrosis factor-α(TNF-α)-tumor necrosis factor receptor 1(TNFR1)-caspase-8 and integrin β1/Akt signaling pathways in a rat model of cervical intervertebral disc degeneration caused by unbalanced dynamic and static forces.METHODS: Thirty-two Sprague-Dawley rats were included in this study, of which 24 rats underwent surgery to induce cervical intervertebral disc degeneration, while eight rats received EA treatment at Dazhui(GV 14). Immunohistochemical staining was used to detect TNF-α, TNFR1, and caspase-8Apoptosis of AF cells was examined with terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling(TUNEL) staining. The m RNA and protein expression levels of integrin β1 andAkt were evaluated with real-time polymerase chain reaction and western blot analysis, respectively.RESULTS: Treatment with EA decreased TUNEL-positive AF cells and lowered TNF-α, TNFR1 and caspase-8 positive cells compared with control groups. EA treatment also increased integrin β1and Akt m RNA and protein levels compared with controls.CONCLUSION: Treatment with EA inhibits AF cell apoptosis through suppression of the TNF-α-TNFR1-caspase-8 signal pathway and increases the expression of integrin β1 and Akt. EA may be a good alternative therapy for treating cervical spondylosis.
基金the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0404)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA20020401)+1 种基金the National Natural Science Foundation of China(31770650)the Fundamental Research Funds for the Central Universities.
文摘Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions.As reproductive organs,unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism.To date,little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers.We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination(the early,blooming and late stages)via transcriptional sequencing as well as metabolite content and phenotypic analysis.We found that a large number of sex-biased genes,rather than sex-limited genes,were responsible for sexual dimorphism in S.paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development.The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages.Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes.These sex-biased genes were involved mainly in signal transduction,photosynthesis,respiration,cell proliferation,phytochrome biosynthesis,and phenol metabolism;therefore,they resulted in more biomass accumulation and higher energy consumption in male catkins.Our results indicated that sex-biased gene expression in S.paraplesia flowers is associated with different reproductive investments in unisexual flowers;male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.
基金financially supported by the Natural Science Foundation of China (Nos. 21502223, 81773580)
文摘Phosphorylated di-,tri-and tetra-saccharides ofβ-1,2-mannan antigen derived from Candida albicans(C.albicans)cell wall were synthesized and covalently conjugated with keyhole limpet hemocyanin(KLH)and human serum albumin(HSA)via a bifunctional linker under mild conditions.The semi-syntheticβ-1,2-mannoside–KLH conjugates were evaluated for the immunization of BALB/c mice.The ELISA results revealed that all three conjugates could elicit high levels of specific IgG antibodies and the acquired antisera could effectively identify theβ-1,2-mannan epitope.Furthermore,the immunofluorescence and flow cytometry assays also uncovered that the induced antibodies,especially that obtained from immunization withβ-1,2-mannotriose–KLH conjugate(1b),could bind well to fungi cell.Eventually,the structure–immunogenicity relationship analysis ofβ-mannan showed that the length of oligo-β-mannoses had a big impact on their immunogenicity andβ-1,2-mannotriose showed the strongest immunogenicity.The results suggested the great potential ofβ-1,2-mannotriose–KLH conjugate as an antifungal vaccine candidate.
基金financial support provided by the National Natural Science Foundation of Shanghai(No.20ZR1420000)Shanghai Shen Kang Center Research Physician Training Program on Innovation and Translation Capabilities(No.SHDC2022CRS051)Three-Year Action Plan for Improving Clinical Research Capacity of International Peace Maternal and Child Health Hospital,Shanghai Jiao Tong University School of Medicine(No.IPMCH2022CR1-05).
文摘Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.
基金Supported by the National Natural Science Foundation of China under Grant No 61674073the Science and Technology Planning Project of Guangdong Province under Grant No 2017A050506056+1 种基金the Key Basic and Applied Research Project of Guangdong Province under Grant No 2016KZDXM021the Project of International as well as Hongkong,Macao and Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province under Grant No 2015KGJHZ028
文摘Doping is an effective approach for improving the photovoltaic performance of Cu2 ZnSnS4（CZTS）. The doping by substitution of Cu atoms in CZTS with Li and Ag atoms is investigated using density functional theory. The results show that the band gaps of Li（2 x）Cu2（1-x）ZnSnS4 and Ag（2 x）Cu2（1-x）ZnSnS4 can be tuned in the ranges of 1.30-3.43 and 1.30-1.63 eV, respectively. The calculation also reveals a phase transition from kesterite to wurtzite-kesterite for Li（2 x）Cu2（1-x）ZnSnS4 as x is larger than 0.9. The tunable band gaps of Li（2 x）Cu2（1-x）ZnSnS4 and Ag（2 x）Cu2（1-x） ZnSnS4 make them beneficial for achieving band-gap-graded solar cells.
文摘BACKGROUND Although acute graft-vs-host disease(aGvHD)is a rare complication of liver transplantation,it is poorly understood and has an extremely high mortality rate.No standardized diagnostic criteria or treatment regimens currently exist.CASE SUMMARY The present study investigated the etiology,diagnosis,and treatment of aGvHD following liver transplantation.Presentation,diagnosis,disease course,histology,and treatment of an aGvHD case are reported,and associated literature is reviewed.A 64-year-old female required LTx due to primary biliary cirrhosis.The donor was a 12-year-old male.Three weeks following liver transplantation,the recipient developed pyrexia,diarrhea,rashes,and antibiotic-unresponsive pancytopenia.Clinical symptoms together with laboratory investigations suggested a diagnosis of aGvHD,which was confirmed via peripheral blood fluorescent in situ hybridization.Donor XY chromosome fluorescent in situ hybridization indicating early chimerism achieved 93%sensitivity in the detection of GvHD.Existing immunosuppressants were discontinued,and high-dose intravenous methylprednisolone was initiated along with antibiotics.While diarrhea resolved,the patient’s general condition continued to deteriorate until demise due to multi-system organ failure at 37 d post-liver transplantation.This case illustrates the life-threatening nature of aGvHD.CONCLUSION Herein,we have summarized a post-LTx aGvHD case and reviewed associated literature in order to increase awareness and provide potentially risk-mitigating recommendations.
基金the support of the research from the fourth batch of postgraduate key courses of Chongqing University (project number:201704008)"the research & practice of software engineering talent evaluation and improvement" of the key project of the teaching reform in Chongqing city (project number:162004)
文摘The culture of professional degree graduate students is a new form of postgraduate education in China. It focuses on cultivating high-level and applied talents compared with original academic degree graduate students. Considering about the source of full-time professional degree graduate students in domain of software engineering and the current college educational system, this paper makes a few beneficial explorations about curriculum, practice teaching, process management and puts forward the mode and method to improve full-time professional degree graduate education in domain of Software Engineering.
文摘Objective: To observe the changes on skin wheal and erythema of skin prick test for the patients with allergic rhinitis during SLIT. Methods: Since March 2010 the 103 cases of SLIT attacked by allergic rhinitis patients, divided into four age groups, respectively measured the diameter of skin wheal and erythema before treatment, six months, one year and 2 years after SLIT. The data were analyzed by analysis of variance method;P Results: The results showed that the most changes of skin erythema diameter were statistically significant in N1, N2, N3 age group during test observation compare with the data before SLIT (p Conclusion: Although most of the skin test wheal did not change significantly during the treatment of SLIT, the erythema reaction decreased to a certain extent, indicating that the intensity of histamine release may be reduced during the treatment.
基金supported by a grant from the National Natural Science Foundation of China(Grants 32330004 to X.S.,and 32170130 to Y.W.)the Shanxi Fundamental Science Research Project for Chemistry&Biology(Grant No.22JHZ008 to X.S.)the Ningbo Top Medical and Health Research Program(No.2023020713 to X.S.).
文摘The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health.Carbapenem‐resistant Enterobacteriaceae(CRE),particularly those producing New Delhi Metallo‐β‐lactamase(NDM‐CRE),are prevalent in livestock and have acquired resistance to nearly all commonly used β‐lactam antibiotics.This study evaluated the efficacy of the antimicrobial peptide BMAP‐27B,a derivative of the cathelicidin family,against NDM‐CRE strains in food animals.BMAP‐27B showed potent antibacterial activity and rapid bactericidal effects against CRE,as well as comparable effects against human carbapenem‐resistant Acinetobacter baumannii.Furthermore,BMAP‐27B effectively penetrated and cleared biofilms formed by virulent strains of Escherichia coli and Klebsiella pneumoniae.Mechanistic studies indicated that BMAP‐27B exerts its antibacterial activity by disrupting bacterial membranes and inhibiting bacterial energy metabolism.BMAP‐27B effectively enhances the efficacy of carbapenems against NDM‐positive isolates by inhibiting efflux pump activity and chelating Zn^(2+) to inhibit NDM proteases,thus reversing carbapenem resistance in NDM‐CRE.Importantly,BMAP‐27B maintained excellent antimicrobial stability under extreme pH changes and high salt concentrations,along with resistance to serum and protease degradation.Investigations revealed that BMAP‐27B also shows ideal biocompatibility and therapeutic efficacy in vivo.In summary,the highly potent antibacterial activity of BMAP‐27B,along with its potential role as a broadspectrum antibiotic adjuvant,makes it a promising candidate for combating infections caused by foodborne NDM‐CRE and preventing pathogen transmission at the animal‐human‐environment interface.
基金supported by the National Natural Science Foundation of China(22378004)the Beijing Natural Science Foundation(L242055)Postdoctoral Fellowship Program of CPSF(GZC20230162).
文摘The emergence of novel viral pathogens and the limitations of conventional antiviral therapies necessitate innovative strategies to combat persistent and pandemic threats.This review details the role of viral infections and antiviral nanomedicines,delving into the mechanisms of action and antiviral advantages of nanomedicines,as well as the latest research advances in this field.The review systematically categorizes the mechanisms of antiviral nanodrugs into a framework that integrates previously fragmented knowledge,and innovatively summarizes the unique attributes and advantages of antiviral nanodrugs compared to small-molecule drugs.Nanotherapies are proposed in this review to conclude advanced nanoantivirals(e.g.,light-activated nano-photosensitizers,biomimetic decoys,PROTAC-based degraders,and gene-silencing platforms)and offer a distinctive narrative perspective,with the aim of presenting a merged and integrated overview of nanodrugs.By intuitively highlighting their commonalities in mechanisms or similarities in application methods,readers may better appreciate the innovative characteristics of different antivirals.We further discuss translational challenges and propose interdisciplinary solutions and future directions to accelerate the development of next-generation antiviral strategies.This review aims to inspire transformative research at the nexus of virology,nanotech-nology,and precision medicine.
基金financially supported by the National Natural Science Foundation Project of China(grant numbers:82173101 and 8237262)the Cancer Innovative Research Program of Sun Yat-sen University Can-cer Centerthe 308-Program for Clinical Research of Sun Yat-sen University Cancer Center.
文摘Background:Phenotypic transition is a common resistance mechanism of targeted therapy.While transformations from lung adenocarcinoma(LUAD)to small-cell lung cancer or squamous-cell carcinoma have been extensively studied,the conversion into sarcomatoid carcinoma(SC)is rarely reported.Methods:Genetic and histological examinations were systematically performed on tumor re-biopsy samples ob-tained from patients with advanced EGFR-mutant LUAD who progressed on EGFR-tyrosine kinase inhibitors(TKIs).EGFR wild-type patients were also identified who underwent the rare transformation from adenocarci-noma to SC following the ineffectiveness of inhibitors that target distinct driver oncogenes.Furthermore,we also retrospectively collected 42 cases diagnosed with primary pulmonary SC as a comparison cohort to comprehen-sively characterize the biological events and clinical outcomes of transformed SC.Results:The sarcomatoid transformation mediated drug resistance in 2.5%and 4.8%of patients after failure on the first/second,and third-generation EGFR-TKIs.Transformation of sarcomatoid carcinoma is characterized by a higher frequency of TP53,RB1,and MET genetic alterations compared to cases lacking histological transforma-tion;the PI3K signaling pathway was also significantly activated.Fifteen individuals were identified with a rare transition from adenocarcinoma to SC,consisting of seven cases with EGFR-activating mutations and eight cases without EGFR mutations.All sarcomatoid-transformed samples not only retained their original driver mutations but also shared specific genetic alterations with primary LUAD.Moreover,transformed sarcomatoid carcinomas mimic the primary SC in terms of immunochemical and molecular features.Conclusions:The transformation from lung adenocarcinoma to SC is a resistance mechanism wildly applied to inhibitors targeting different driver oncogenes.Immunotherapy plus chemotherapy shows potential to benefit patients with sarcomatoid transformation and warrants further study in larger cohorts.
基金supported by National Key R&D Program of China (No.2022YFC3501700)National Natural Science Foundation of China (No.82274059)+3 种基金Naval Military Medical University,Far East Talent Project (No.SL-33)Talent Project established by Chinese Pharmaceutical Association Hospital Pharmacy department (No.CPA-Z05-ZC-2024-003)Shanghai Oriental Talent Plan Youth Program (formerly Shanghai Young Top-Notch Talent) (2023)the Baoshan District Medical Key Science (Specialty) and Specialty Brand Construction Project (No.BSZK-2023-A12)。
文摘Overproduction of reactive oxygen species(ROS) following ischemic injury triggers an inflammatory response,significantly impeding neurological functional recovery.Nanozymes with potent antioxidative and anti-inflammatory effects thus offer great potential for ischemic stroke treatment.In this study,we developed an ischemia-homing nanozyme by combining melatonin(MT)-loaded honeycomb manganese dioxide(MnO_(2)) nanoflowers with M2-type microglia membranes to rescue the ischemic penumbra.The surface-engineered M2-type microglia membranes provided intrinsic ischemia-homing and blood-brain barrier(BBB)-crossing properties to the biomimetic nanozymes.This nanozyme can not only transforms harmfulsuperoxide anion radicals(^(·)O^(2-)) and hydrogen peroxide(H_(2)O_(2)) into harmless water and oxygen but also scavenges highly toxic hydroxyl radicals(^(·)OH),dramatically lowering intracellular ROS levels.More importantly,the biomimetic nanoparticles reduce cerebral infarct areas and provide significant neuroprotection against ischemic stroke by lowering oxidative stress,inhibiting cell apoptosis,and decreasing inflammation.This study may offer a viable approach for the use of nanozymes in treating ischemic stroke.
文摘本文研究广义部分线性单指标模型(generalized partially linear single-index models,GPLSIMs)的模型平均问题.在实际应用中,GPLSIMs由于其灵活性和易解释性受到广泛关注.然而,GPLSIMs在应用中存在两类不确定性:变量的不确定性和单指标连接函数光滑度的不确定性.为了解决该不确定性问题,本文提出一种GPLSIMs的最优模型平均方法,该方法通过最大交叉验证准则得到数据驱动的权重.在模型误设定假设和发散模型空间的框架下,本文证明在最小化Kullback-Leibler(KL)损失准则下,所提出的模型平均估计渐近最优.同时,当候选模型集中存在伪真模型时,本文证明基于交叉验证准则得到的权重渐近地集中在伪真模型上.此外,基于提出的模型平均方法,本文为GPLSIMs构建了一种变量重要性度量,并证明该度量可以渐近识别所有真实模型中的变量.模拟研究和两个实际数据分析均展示了本文提出的方法相对于几种现有方法的优势.
