This paper is extracted from President ofthe State Power Corporation(SP),Gao Yan's speech atthe WorkingConference 2002 held on January 16-18 in Tianjin.It summarizes and analyses the Corporation's various task...This paper is extracted from President ofthe State Power Corporation(SP),Gao Yan's speech atthe WorkingConference 2002 held on January 16-18 in Tianjin.It summarizes and analyses the Corporation's various tasks andoperating activities in 2001 and puts forwaad major targets and focal tas ks fôr 2002.展开更多
The Chinese Academy of Sci-ences (CAS) has begun introducingthe trial implementation of theKnowledge Innovation Program(KIP)in an all-round manner just as,at the beginning of the new century,the state is about to impl...The Chinese Academy of Sci-ences (CAS) has begun introducingthe trial implementation of theKnowledge Innovation Program(KIP)in an all-round manner just as,at the beginning of the new century,the state is about to implement itsTenth Five-Year Plan for thecountry’s ongoing economic andsocial development. This will展开更多
This paper looks back upon the achievements of the electric power industry during the Ninth Five-year Plan Period(1996-2000), and puts forward the developing targets and the working focuses for the Tenth Five-year Pla...This paper looks back upon the achievements of the electric power industry during the Ninth Five-year Plan Period(1996-2000), and puts forward the developing targets and the working focuses for the Tenth Five-year Plan Period(2001-2005).展开更多
Renewable energy (RE) has been attached high attention around the world due to its carbon-free and indigenous production in a sustainable way. China enjoys plenty of renewable energy resources, particularly the wind, ...Renewable energy (RE) has been attached high attention around the world due to its carbon-free and indigenous production in a sustainable way. China enjoys plenty of renewable energy resources, particularly the wind, solar, hydro- and biomass energy, which could be a sound basis for a large-scale exploitation. This report examines the current status of RE technology and industry, analyzes the challenges of promoting RE in China. In order to pave the way for a long-term development of RE, this paper outlines the basic principles and priorities for individual RE technology. In line with these, the paper puts forward the RE targets and further describes the RE road map by 2020, 2030 and extend to 2050, taking consideration of China’s RE resources, industrial basis and energy demand etc. At last, this paper provides some recommendations to ensure the achievements of the RE targets.展开更多
This paper presents the guidelines and basic ideas for working out the development plan of new and renewable energy based upon China’s conditions, the foundation of industrialization development, targets of developme...This paper presents the guidelines and basic ideas for working out the development plan of new and renewable energy based upon China’s conditions, the foundation of industrialization development, targets of development for year 2000-2015 and the main tasks of industrialization system construction.展开更多
Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the dis...Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.展开更多
This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving aca...This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.展开更多
Targeted poverty alleviation is a wise and far-reaching basic national policy formulated by the Chinese people under the leadership of the Communist Party of China. It is a strategic project and strategic goal for the...Targeted poverty alleviation is a wise and far-reaching basic national policy formulated by the Chinese people under the leadership of the Communist Party of China. It is a strategic project and strategic goal for the Chinese people to completely shake off poverty and backwardness and move towards a prosperous and powerful country,as well as the historical mission of socialism to defeat capitalism. However,targeted poverty alleviation is a grand project involving the entire society. To ensure the ultimate realization of the goal of targeted poverty alleviation,only policies and programs are far from enough. Corresponding legal systems must also be established,which is the fundamental condition for targeted poverty alleviation and sustainable development.展开更多
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, w...Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, while Zhenbao Pills (ZBP) from traditional Chinese medicine may enhance recovery from neurological disorders. Further investigations into the mechanisms of ZBP are crucial for better stroke management.Methods: This research accessed databases to pinpoint the core components and identify the targets of ZBP and stroke. "Drug-component-target" networks were established, followed by enrichment analysis of identified targets. We also used Mendelian randomization (MR) to assess causal relationships between feature genes and stroke incidence, for which colocalization was employed for validation. Furthermore, molecular docking and Gene Expression Omnibus (GEO) datasets were used for preliminary confirmation.Results: This study identified 14 core components and 105 stroke-related targets for ZBP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are involved mainly in oxidative stress processes, lipid metabolism, and the PI3K-Akt signaling pathway. Correlation with stroke risk was determined through MR analysis, which revealed that the VEGFA and ARG1 genes were negatively correlated with stroke risk and GATM was positively correlated. Additionally, the stable interactions of molecular docking and differential expression of key genes support their potential therapeutic relevance.Conclusion: Stroke may be mitigated through essential constituents of ZBP (e.g., luteolin, quercetin, and isorhamnetin) that target pivotal genes (e.g., VEGFA, ARG1, and GATM), including characteristic genes, and the modulation of oxidative stress and inflammation-related pathways. These discoveries hold important implications for clinical practice and future research endeavors.展开更多
Introduction:In China,the prevalence of abnormal spinal curvature in children and adolescents is high and the number of cases is increasing in recent years,which seriously threatens physical and mental health of child...Introduction:In China,the prevalence of abnormal spinal curvature in children and adolescents is high and the number of cases is increasing in recent years,which seriously threatens physical and mental health of children and adolescents.Public health surveillance of these abnormalities is crucial for developing targeted interventions.Methods:This study evaluated detection rates and risk factors of spinal curvature abnormalities among children and adolescents in Jiangsu Province,China.This study analyzed data from the population-based“Surveillance for Common Disease and Health Risk Factors Among Students”project,implemented annually from September to November during 2021–2023.Abnormal spinal curvature was assessed using the national“Technical Guide for Prevention and Control of Abnormal Spinal Curvature in Children and Adolescents.”Detection rates were calculated,and associated factors were evaluated using multivariate logistic regression.Results:Annual detection rates were 2.6%,1.8%,and 2.3%,respectively,among children and adolescents aged 6–17 years.Detection rates increased with age and were significantly higher among females compared to males.Adequate physical activity,sufficient sleep,and correct reading and writing postures were protective factors against spinal curvature abnormalities,while low body weight was associated with increased risk.Conclusion:The emerging burden of abnormal spinal curvature necessitates targeted public health interventions,particularly for high school students and females.Beyond implementing early lifestyle interventions such as sufficient outdoor activities,appropriate referrals to public health specialists and orthopedic surgeons may provide additional risk mitigation.Successful outcomes require multisectoral collaboration and parental engagement to achieve sustainable public health improvements.展开更多
Significant heterogeneity exists in hormone receptor(HR)-positive/HER2-positive(HR+/HER2+)breast cancer,contributing to suboptimal pathological complete response rates with conventional neoadjuvant treatment regimens....Significant heterogeneity exists in hormone receptor(HR)-positive/HER2-positive(HR+/HER2+)breast cancer,contributing to suboptimal pathological complete response rates with conventional neoadjuvant treatment regimens.Overcoming this challenge requires precise molecular classification,which is pivotal for the development of targeted therapies.We conducted molecular typing on a cohort of 211 patients with HR^(+)/HER2^(+) breast cancer and performed a comprehensive analysis of the efficacy of various neoadjuvant treatment regimens.Our findings revealed four distinct molecular subtypes,each exhibiting unique characteristics and therapeutic implications.The HER2-enriched subtype,marked by activation of the HER2 signaling and hypoxiainducible factor 1(HIF-1)pathway,may benefit from intensified anti-HER2-targeted therapy.Estrogen receptor(ER)-activated subtype demonstrated potential sensitivity to combined therapeutic strategies targeting both ER and HER2 pathways.Characterized by high immune cell infiltration,the immunomodulatory subtype showed sensitivity to HER2-targeted antibody-drug conjugates(ADCs)and promise for immune checkpoint therapy.The highly heterogeneous subtype requires a multifaceted therapeutic approach.Organoid susceptibility assays suggested phosphoinositide 3-kinase inhibitors may be a potential treatment option.These findings underscore the importance of molecular subtyping in HR^(+)/HER2^(+) breast cancer,offering a framework for developing precise and personalized treatment strategies.By addressing the heterogeneity of the disease,these approaches have the potential to optimize therapeutic outcomes and improve patient care.展开更多
How 60 years of targeted development have brought modernization and prosperity to the people of Xizang,n August 25,Tarob Yonden Tsomo was busy at her cafe in Lhasa,capital of Xizang Autonomous Region,working from earl...How 60 years of targeted development have brought modernization and prosperity to the people of Xizang,n August 25,Tarob Yonden Tsomo was busy at her cafe in Lhasa,capital of Xizang Autonomous Region,working from early morning until late at night.“Today is the Shoton Festival holiday,so the cafe is even busier-Fve been working nonstop,”she told Beijing Review.展开更多
Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implication...Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.展开更多
The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we disco...The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we discovered that the activated NLRP3 inflammasome complex(disc-NLRP3)and the activating mutation L351P exhibited resistance to MCC950.Through investigations using the small-molecule compound polydatin,HSP90αwas found to stabilize both the resting(cage-NLRP3)and activated state(disc-NLRP3)of NLRP3 complexes,sustaining its activation.Our mechanistic studies revealed that polydatin specifically targets HSP90α,binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction.This disruption leads to the dissipation of cage-NLRP3,disc-NLRP3 complexes and NLRP3 L351P.Importantly,genetic and pharmacological inactivation of HSP90αeffectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis.These therapeutic effects highlight the clinical potential of HSP90αinhibition.Our findings demonstrate that HSP90αis crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation,and targeting HSP90αrepresents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.展开更多
There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronav...There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronavirus disease 2019(COVID-19)is a viral infection causing symptoms like dry cough,sore throat,nasal congestion,tiredness,fever,loss of taste,and smell etc.The disease was first reported in Wuhan,China,in December 2019.The infection is caused by SARS-CoV-2,which is the third introduction of a highly pathogenic coronavirus into the human population.Coronaviruses are viruses with a positive RNA envelope assigned toα,β,γ,andδgenera.Moreover,SARS-CoV-2 belongs to theβgenus.The four structural proteins ofβcoronavirus are membrane(M),envelope(E),spike(S),and nucleocapsid(N)protein,mediation of coronavirus host infection is established by spike(S)protein.Therefore,the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic.It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor,viral RNA synthesis and replication,3CLpro,RdRp,and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection.Furthermore,the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development.Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19,and mRNA-1273 targeting spike protein is the promising vaccine.However,as patient management and drug repositioning are taking place,it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection,to develop novel therapeutics.展开更多
文摘This paper is extracted from President ofthe State Power Corporation(SP),Gao Yan's speech atthe WorkingConference 2002 held on January 16-18 in Tianjin.It summarizes and analyses the Corporation's various tasks andoperating activities in 2001 and puts forwaad major targets and focal tas ks fôr 2002.
文摘The Chinese Academy of Sci-ences (CAS) has begun introducingthe trial implementation of theKnowledge Innovation Program(KIP)in an all-round manner just as,at the beginning of the new century,the state is about to implement itsTenth Five-Year Plan for thecountry’s ongoing economic andsocial development. This will
文摘This paper looks back upon the achievements of the electric power industry during the Ninth Five-year Plan Period(1996-2000), and puts forward the developing targets and the working focuses for the Tenth Five-year Plan Period(2001-2005).
文摘Renewable energy (RE) has been attached high attention around the world due to its carbon-free and indigenous production in a sustainable way. China enjoys plenty of renewable energy resources, particularly the wind, solar, hydro- and biomass energy, which could be a sound basis for a large-scale exploitation. This report examines the current status of RE technology and industry, analyzes the challenges of promoting RE in China. In order to pave the way for a long-term development of RE, this paper outlines the basic principles and priorities for individual RE technology. In line with these, the paper puts forward the RE targets and further describes the RE road map by 2020, 2030 and extend to 2050, taking consideration of China’s RE resources, industrial basis and energy demand etc. At last, this paper provides some recommendations to ensure the achievements of the RE targets.
文摘This paper presents the guidelines and basic ideas for working out the development plan of new and renewable energy based upon China’s conditions, the foundation of industrialization development, targets of development for year 2000-2015 and the main tasks of industrialization system construction.
文摘Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.
文摘This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.
文摘Targeted poverty alleviation is a wise and far-reaching basic national policy formulated by the Chinese people under the leadership of the Communist Party of China. It is a strategic project and strategic goal for the Chinese people to completely shake off poverty and backwardness and move towards a prosperous and powerful country,as well as the historical mission of socialism to defeat capitalism. However,targeted poverty alleviation is a grand project involving the entire society. To ensure the ultimate realization of the goal of targeted poverty alleviation,only policies and programs are far from enough. Corresponding legal systems must also be established,which is the fundamental condition for targeted poverty alleviation and sustainable development.
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
基金funded by the 2021 Inner Mongolia Higher Education Scientific Research Project(NJZY21063)the 2023 Project of the Natural Science Foundation of the Inner Mongolia Autonomous Region(2023LHMS08081).
文摘Background: Stroke causes substantial death and disability worldwide, challenging healthcare systems and impacting patients' lives. Research on stroke biomarkers can aid in the development of targeted therapies, while Zhenbao Pills (ZBP) from traditional Chinese medicine may enhance recovery from neurological disorders. Further investigations into the mechanisms of ZBP are crucial for better stroke management.Methods: This research accessed databases to pinpoint the core components and identify the targets of ZBP and stroke. "Drug-component-target" networks were established, followed by enrichment analysis of identified targets. We also used Mendelian randomization (MR) to assess causal relationships between feature genes and stroke incidence, for which colocalization was employed for validation. Furthermore, molecular docking and Gene Expression Omnibus (GEO) datasets were used for preliminary confirmation.Results: This study identified 14 core components and 105 stroke-related targets for ZBP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are involved mainly in oxidative stress processes, lipid metabolism, and the PI3K-Akt signaling pathway. Correlation with stroke risk was determined through MR analysis, which revealed that the VEGFA and ARG1 genes were negatively correlated with stroke risk and GATM was positively correlated. Additionally, the stable interactions of molecular docking and differential expression of key genes support their potential therapeutic relevance.Conclusion: Stroke may be mitigated through essential constituents of ZBP (e.g., luteolin, quercetin, and isorhamnetin) that target pivotal genes (e.g., VEGFA, ARG1, and GATM), including characteristic genes, and the modulation of oxidative stress and inflammation-related pathways. These discoveries hold important implications for clinical practice and future research endeavors.
基金Supported by Ministry of Science and Technology(Grant No.G2023141005L)Ministry of Education(Grant No.1125000172)+2 种基金Jiangsu Provincial Social Science Foundation(Grant No.24SHB005)SEU Innovation Capability Enhancement Plan for Doctoral Students(Grant No.CXJH_SEU 25220)Jiangsu Provincial Department of Science and Technology.
文摘Introduction:In China,the prevalence of abnormal spinal curvature in children and adolescents is high and the number of cases is increasing in recent years,which seriously threatens physical and mental health of children and adolescents.Public health surveillance of these abnormalities is crucial for developing targeted interventions.Methods:This study evaluated detection rates and risk factors of spinal curvature abnormalities among children and adolescents in Jiangsu Province,China.This study analyzed data from the population-based“Surveillance for Common Disease and Health Risk Factors Among Students”project,implemented annually from September to November during 2021–2023.Abnormal spinal curvature was assessed using the national“Technical Guide for Prevention and Control of Abnormal Spinal Curvature in Children and Adolescents.”Detection rates were calculated,and associated factors were evaluated using multivariate logistic regression.Results:Annual detection rates were 2.6%,1.8%,and 2.3%,respectively,among children and adolescents aged 6–17 years.Detection rates increased with age and were significantly higher among females compared to males.Adequate physical activity,sufficient sleep,and correct reading and writing postures were protective factors against spinal curvature abnormalities,while low body weight was associated with increased risk.Conclusion:The emerging burden of abnormal spinal curvature necessitates targeted public health interventions,particularly for high school students and females.Beyond implementing early lifestyle interventions such as sufficient outdoor activities,appropriate referrals to public health specialists and orthopedic surgeons may provide additional risk mitigation.Successful outcomes require multisectoral collaboration and parental engagement to achieve sustainable public health improvements.
基金supported by the National Natural ScienceFoundation of China(Grant Nos.U20A20381,82203804,82403918)the National Natural ScienceFoundation of Liaoning Province(Grant No.2024-MS-053)China Medical Education Association Subject(2016001).
文摘Significant heterogeneity exists in hormone receptor(HR)-positive/HER2-positive(HR+/HER2+)breast cancer,contributing to suboptimal pathological complete response rates with conventional neoadjuvant treatment regimens.Overcoming this challenge requires precise molecular classification,which is pivotal for the development of targeted therapies.We conducted molecular typing on a cohort of 211 patients with HR^(+)/HER2^(+) breast cancer and performed a comprehensive analysis of the efficacy of various neoadjuvant treatment regimens.Our findings revealed four distinct molecular subtypes,each exhibiting unique characteristics and therapeutic implications.The HER2-enriched subtype,marked by activation of the HER2 signaling and hypoxiainducible factor 1(HIF-1)pathway,may benefit from intensified anti-HER2-targeted therapy.Estrogen receptor(ER)-activated subtype demonstrated potential sensitivity to combined therapeutic strategies targeting both ER and HER2 pathways.Characterized by high immune cell infiltration,the immunomodulatory subtype showed sensitivity to HER2-targeted antibody-drug conjugates(ADCs)and promise for immune checkpoint therapy.The highly heterogeneous subtype requires a multifaceted therapeutic approach.Organoid susceptibility assays suggested phosphoinositide 3-kinase inhibitors may be a potential treatment option.These findings underscore the importance of molecular subtyping in HR^(+)/HER2^(+) breast cancer,offering a framework for developing precise and personalized treatment strategies.By addressing the heterogeneity of the disease,these approaches have the potential to optimize therapeutic outcomes and improve patient care.
文摘How 60 years of targeted development have brought modernization and prosperity to the people of Xizang,n August 25,Tarob Yonden Tsomo was busy at her cafe in Lhasa,capital of Xizang Autonomous Region,working from early morning until late at night.“Today is the Shoton Festival holiday,so the cafe is even busier-Fve been working nonstop,”she told Beijing Review.
基金supported by the National Natural Science Foundation of China(No.81902701 to Y.L.,82103649 to H.Z.)the Natural Science Foundation of Liaoning Province,China(No.20180530037 to Y.L.,2022-MS-183 to W.D.).
文摘Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.
基金supported by the National Natural Science Foundation of China(82273933,82073856,82230116,and 82473929)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(no.ZYYCXTD-C-202208)Fundamental Research Funds for the Central Universities(020814380199).
文摘The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we discovered that the activated NLRP3 inflammasome complex(disc-NLRP3)and the activating mutation L351P exhibited resistance to MCC950.Through investigations using the small-molecule compound polydatin,HSP90αwas found to stabilize both the resting(cage-NLRP3)and activated state(disc-NLRP3)of NLRP3 complexes,sustaining its activation.Our mechanistic studies revealed that polydatin specifically targets HSP90α,binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction.This disruption leads to the dissipation of cage-NLRP3,disc-NLRP3 complexes and NLRP3 L351P.Importantly,genetic and pharmacological inactivation of HSP90αeffectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis.These therapeutic effects highlight the clinical potential of HSP90αinhibition.Our findings demonstrate that HSP90αis crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation,and targeting HSP90αrepresents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.
文摘There is little or no research initiated on enlightening Nigerians about the pathogenesis,targets for drug development and repositioning for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronavirus disease 2019(COVID-19)is a viral infection causing symptoms like dry cough,sore throat,nasal congestion,tiredness,fever,loss of taste,and smell etc.The disease was first reported in Wuhan,China,in December 2019.The infection is caused by SARS-CoV-2,which is the third introduction of a highly pathogenic coronavirus into the human population.Coronaviruses are viruses with a positive RNA envelope assigned toα,β,γ,andδgenera.Moreover,SARS-CoV-2 belongs to theβgenus.The four structural proteins ofβcoronavirus are membrane(M),envelope(E),spike(S),and nucleocapsid(N)protein,mediation of coronavirus host infection is established by spike(S)protein.Therefore,the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic.It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor,viral RNA synthesis and replication,3CLpro,RdRp,and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection.Furthermore,the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development.Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19,and mRNA-1273 targeting spike protein is the promising vaccine.However,as patient management and drug repositioning are taking place,it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection,to develop novel therapeutics.
