The self-charging concept has drawn considerable attention due to its excellent ability to achieve environmental energy harvesting,conversion and storage without an external power supply.However,most self-charging des...The self-charging concept has drawn considerable attention due to its excellent ability to achieve environmental energy harvesting,conversion and storage without an external power supply.However,most self-charging designs assembled by multiple energy harvesting,conversion and storage materials increase the energy transfer loss;the environmental energy supply is generally limited by climate and meteorological conditions,hindering the potential application of these selfpowered devices to be available at all times.Based on aerobic autoxidation of catechol,which is similar to the electrochemical oxidation of the catechol groups on the carbon materials under an electrical charge,we proposed an air-breathing chemical self-charge concept based on the aerobic autoxidation of catechol groups on oxygen-enriched carbon materials to ortho-quinone groups.Energy harvesting,conversion and storage functions could be integrated on a single carbon material to avoid the energy transfer loss among the different materials.Moreover,the assembled Cu/oxygen-enriched carbon battery confirmed the feasibility of the air-oxidation self-charging/electrical discharging mechanism for potential applications.This air-breathing chemical self-charge concept could facilitate the exploration of high-efficiency sustainable air self-charging devices.展开更多
Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence ...Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.展开更多
Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy ...Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.展开更多
In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most...In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most effective strategy to solve the pandemic crisis.SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2(ACE2)via the receptor-binding domain(RBD)of the surface spike(S)glycoprotein.In this study,a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells.The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody.Furthermore,the specific antibody titer and virus-neutralizing antibody(NAb)titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)_(3) and CpG.Our results showed that the virus-NAb lasted for more than six months in mice.To summarize,we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris,which stimulates neutralizing and protective antibody responses.A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.展开更多
With the rapid growth of network technology, the methods and types of cyber-attacks are increasing rapidly. Traditional static passive defense technologies focus on external security and known threats to the target sy...With the rapid growth of network technology, the methods and types of cyber-attacks are increasing rapidly. Traditional static passive defense technologies focus on external security and known threats to the target system and cannot resist advanced persistent threats. To solve the situation that cyberspace security is easy to attack and difficult to defend, Chinese experts on cyberspace security proposed an innovative theory called mimic defense, it is an active defense technology that employs “Dynamic, Heterogeneous, Redundant” architecture to defense attacks. This article first briefly describes the classic network defense technology and Moving Target Defense (MTD). Next, it mainly explains in detail the principles of the mimic defense based on the DHR architecture and analyzes the attack surface of DHR architecture. This article also includes applications of mimic defense technology, such as mimic routers, and mimic web defense systems. Finally, it briefly summarizes the existing research on mimic defense, expounds the problems that need to be solved in mimic defense, and looks forward to the future development of mimic defense.展开更多
Silver nanoparticles(AgNPs)are widely used in antimicrobial applications.However,its easy aggregation and rapid loss hinder the effective antifouling.To address this issue,a novel stimuli-responsive antibacterial nano...Silver nanoparticles(AgNPs)are widely used in antimicrobial applications.However,its easy aggregation and rapid loss hinder the effective antifouling.To address this issue,a novel stimuli-responsive antibacterial nanocomposite(Ag@SP-MSN)was developed based on spiropyran covalently conjugated mesoporous silica nanoparticles(284.6 nm)and AgNPs(27.1 nm)via strong electrostatic attraction.Both transmission electron microscopy(TEM)and atomic force microscopy(AFM)images proved the successful modification of AgNPs onto SP-MSN.The light-induced maximum loading amount towards AgNPs was calculated to be 95.0 wt.%after ultraviolet irradiation,while the amount of AgNPs released from Ag@SP-MSN was 94.4 wt.%under visible light in the aid of ammonia(0.1%,v/v).Upon cycled light irradiation,Ag@SP-MSN could recover 84.5 wt.%of AgNPs even after four cycles.The proposed Ag@SP-MSN exhibited better antibacterial activity against both E.coli and S.aureus than Ag@MSN under visible light illumination,indicating the efficient photo-responsive isomerization of spiropyran.Furthermore,the Ag@SP-MSN embedded gel demonstrated outstanding antifouling ability even after 21 days when compared to AgNPs gel.The long-term photo-controllable antifouling property proved the excellent reversible absorption and release of Ag@SP-MSN towards AgNPs.This work provides new insights into the safe utilization of nanomaterials,offering promising advancements to meet clinical antibacterial requirements.展开更多
Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo e...Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global health.OPXV includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).展开更多
Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012...Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.展开更多
The emergence of the"Ancient State"is considered an important stage in the discourse on human civilizations.Based on its complex and hierarchical social structure,the Shuanghuaishu site of Henan Province is ...The emergence of the"Ancient State"is considered an important stage in the discourse on human civilizations.Based on its complex and hierarchical social structure,the Shuanghuaishu site of Henan Province is regarded as an"Ancient state",specifically the"Heluo Ancient State".The site is situated in the middle reaches of the Yellow River region and played a key role in prehistoric China.However,the reasons behind its decline are unclear.Here,we conducted an integrated investigation of the archaeological excavations and archaeoseismic analyses at the Shuanghuaishu site.We identified paleoseismic remains within paleo-artificial moats,which were formed owing to off-fault structures of soil liquefaction,hillslope landslides,and related ground fractures,along with shake-related wall disruption and building collapse in the residential zone.Charcoal dating was conducted to constrain the age for this earthquake event,which was determined to be approximately 5.0 cal kyr BP.Furthermore,based on the practical curve for earthquake-induced liquefaction,the preliminary estimate of the magnitude of this paleo seismic event is greater than M_(s)5.9-6.0.We propose that the Shuanghuaishu site experienced a recession after the earthquake event,which may have influenced the continuous development of the"Heluo Ancient State"as a regional center settlement.展开更多
The undesirable shuttle effect and sluggish redox kinetics of polysulfides seriously result in low sulfur utilization and poor capacity retention.Here,an integrated strategy is proposed by rational designing multifunc...The undesirable shuttle effect and sluggish redox kinetics of polysulfides seriously result in low sulfur utilization and poor capacity retention.Here,an integrated strategy is proposed by rational designing multifunctional architecture to manipulate the redox kinetics of polysulfides,specifically,by employing iron atoms(Fe-As)and iron-species nanoparticles(Fe-NPs)co-embedded nitrogen-doped carbon nanotube(Fe-NCNT)as catalyst and host for sulfur.The synergistic cooperation of Fe-As and Fe-NPs provides efficient active sites to facilitate the diffusion,strengthen the affinities,and promote the conversion reactions for polysulfides.Furthermore,the NCNT not only offers practical Li+transport pathways but also immobilize the polysulfides effectively.Benefiting from these merits,the Fe-NCNT/S electrodes exhibit high initial specific capacity of 1502.6 mAh/g at 0.1 C,outstanding rate performance(830 mAh/g at 2 C),and good cycling performance(597.8 mAh/g after 500 cycles with an ultralow capacity fading rate of 0.069%per cycle).This work features the distinct interaction of iron atom-nanoparticles on facilitating immobilization-diffusion-transformation process of polysulfides,and it also expected to pave the way for the application in practical Li-S batteries.展开更多
Summary What is already known about this topic?Although a third coronavirus disease 2019(COVID-19)vaccination(booster)dose is highly recommended for diabetic patients,the vaccination behaviors and related adverse even...Summary What is already known about this topic?Although a third coronavirus disease 2019(COVID-19)vaccination(booster)dose is highly recommended for diabetic patients,the vaccination behaviors and related adverse events are unclear among diabetic patients with a COVID-19 booster dose.What is added by this report?Diabetic patients with higher postprandial blood glucose,worrying about the safety of the booster dose were less likely to get the vaccine.展开更多
Summary What is already known about this topic?Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)than the general population;however,co...Summary What is already known about this topic?Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)than the general population;however,coverage for booster doses of the coronavirus disease 2019(COVID-19)vaccine was low among cancer patients in China.What is added by this report?Overall,32.0%and 56.4%of cancer patients from four Provincial Level Administrative Divisions(PLADs)expressed hesitancy toward the first and second booster doses,respectively.Factors negatively associated with hesitancy to receive booster doses included positive attitudes,perceived support,and higher exposure to COVID-19 vaccination information.Conversely,postvaccination fatigue was positively associated with vaccine hesitancy.What are the implications for public health practice?Improved COVID-19 vaccination coverage is needed to promote health for cancer patients.展开更多
Aluminum(alum)adjuvant is the most extensively used protein subunit vaccine adjuvant,and its effectiveness and safety have been widely recognized.The surface charge of the antigen determines its electrostatic adsorpti...Aluminum(alum)adjuvant is the most extensively used protein subunit vaccine adjuvant,and its effectiveness and safety have been widely recognized.The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant,which directly affects the immune efficacy of the protein vaccine.In our study,we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptorbinding domain(RBD),achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant.展开更多
Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have ...Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully clarified.Here we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant HCC cells),plays a significant role in sorafenib resistance in HCC.We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib.Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation.Moreover,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells.Using different HCC mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance.Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.展开更多
The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome libr...The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome library screening,we evaluated Kelch-like ECH-associated protein 1(KEAP1)as a key regulator of sorafenib’s susceptibility in HCC.We also investigated whether KEAP1’s knockdown can stabilize nuclear factor(erythroid-derived 2)-like 2(NRF2)protein levels that led to sorafenib’s resistance,including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC’s growth in vitro and in vivo.Furthermore,we clarified that fibroblast growth factor 21(FGF21)is an important downstream regulator of NRF2 in HCC.Intriguingly,we observed that FGF21 bound to NRF2 through the C-terminus of FGF21,thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC.These findings,therefore,propose that targeting FGF21 is a promising strategy to combat HCC sorafenib’s resistance.展开更多
The placement of the Ediacaran-Cambrian boundary in deep-water realm in South China and the high-precision temporal framework for the Ediacaran-Cambrian transition in this region have not yet been completely solved. R...The placement of the Ediacaran-Cambrian boundary in deep-water realm in South China and the high-precision temporal framework for the Ediacaran-Cambrian transition in this region have not yet been completely solved. Recently, we have found two K-bentonite beds in the top of the Liuchapo Formation at the Pingyin section, Guizhou Province. It provides an opportunity for constructing the temporal framework of the transitional strata on the Yangtze Platform in South China and for determining the Ediacaran-Cambrian boundary in this area. In this study, we conducted high-precision CA-ID-TIMS U-Pb dating on zircons from the two K-bentonites. The ages of the two K-bentonites were precisely constrained at 536.40±0.47/1.1/1.2 Ma(2σ, n=7, MSWD=0.92) and 541.48±0.46/1.1/1.2 Ma(2σ, n=8, MSWD=1.3). Combining the geochronological results with organic carbon isotope data of chert in the topmost Liuchapo Formation from the section, we suggest that the EdiacaranCambrian boundary should be consistent with a significant negative organic carbon isotope excursion between the two Kbentonites. The scheme of the Ediacaran-Cambrian boundary in this study is of great significance for global correlation, and further for unravelling the information of the terminal Ediacaran-early Cambrian ocean.展开更多
基金financially supported by the National Natural Science Foundation of China(51503178,52202048,52027801)National Key R&D Program of China(2017YFA0206301)+1 种基金China-Germany Collaboration Project(M-0199)Natural Science Foundation of Hebei Province(B2021203012,E2022203082)。
文摘The self-charging concept has drawn considerable attention due to its excellent ability to achieve environmental energy harvesting,conversion and storage without an external power supply.However,most self-charging designs assembled by multiple energy harvesting,conversion and storage materials increase the energy transfer loss;the environmental energy supply is generally limited by climate and meteorological conditions,hindering the potential application of these selfpowered devices to be available at all times.Based on aerobic autoxidation of catechol,which is similar to the electrochemical oxidation of the catechol groups on the carbon materials under an electrical charge,we proposed an air-breathing chemical self-charge concept based on the aerobic autoxidation of catechol groups on oxygen-enriched carbon materials to ortho-quinone groups.Energy harvesting,conversion and storage functions could be integrated on a single carbon material to avoid the energy transfer loss among the different materials.Moreover,the assembled Cu/oxygen-enriched carbon battery confirmed the feasibility of the air-oxidation self-charging/electrical discharging mechanism for potential applications.This air-breathing chemical self-charge concept could facilitate the exploration of high-efficiency sustainable air self-charging devices.
基金supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919)the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001)Beijing Municipal Science and Technology Commission(Z201100005420024)。
文摘Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
文摘Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.
基金supported by the National Key Research and Development Program of China (2020YFC0841400-008)the National Science and Technology Major Projects(2018ZX09711003-013-002)the National Natural Science Foundation of China (81673339 and 81773619)
文摘In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most effective strategy to solve the pandemic crisis.SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2(ACE2)via the receptor-binding domain(RBD)of the surface spike(S)glycoprotein.In this study,a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells.The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody.Furthermore,the specific antibody titer and virus-neutralizing antibody(NAb)titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)_(3) and CpG.Our results showed that the virus-NAb lasted for more than six months in mice.To summarize,we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris,which stimulates neutralizing and protective antibody responses.A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.
文摘With the rapid growth of network technology, the methods and types of cyber-attacks are increasing rapidly. Traditional static passive defense technologies focus on external security and known threats to the target system and cannot resist advanced persistent threats. To solve the situation that cyberspace security is easy to attack and difficult to defend, Chinese experts on cyberspace security proposed an innovative theory called mimic defense, it is an active defense technology that employs “Dynamic, Heterogeneous, Redundant” architecture to defense attacks. This article first briefly describes the classic network defense technology and Moving Target Defense (MTD). Next, it mainly explains in detail the principles of the mimic defense based on the DHR architecture and analyzes the attack surface of DHR architecture. This article also includes applications of mimic defense technology, such as mimic routers, and mimic web defense systems. Finally, it briefly summarizes the existing research on mimic defense, expounds the problems that need to be solved in mimic defense, and looks forward to the future development of mimic defense.
基金supported by the National Natural Science Foundation of China(No.21804043)the Funding Project of the State Key Laboratory of Bioreactor Engineering.
文摘Silver nanoparticles(AgNPs)are widely used in antimicrobial applications.However,its easy aggregation and rapid loss hinder the effective antifouling.To address this issue,a novel stimuli-responsive antibacterial nanocomposite(Ag@SP-MSN)was developed based on spiropyran covalently conjugated mesoporous silica nanoparticles(284.6 nm)and AgNPs(27.1 nm)via strong electrostatic attraction.Both transmission electron microscopy(TEM)and atomic force microscopy(AFM)images proved the successful modification of AgNPs onto SP-MSN.The light-induced maximum loading amount towards AgNPs was calculated to be 95.0 wt.%after ultraviolet irradiation,while the amount of AgNPs released from Ag@SP-MSN was 94.4 wt.%under visible light in the aid of ammonia(0.1%,v/v).Upon cycled light irradiation,Ag@SP-MSN could recover 84.5 wt.%of AgNPs even after four cycles.The proposed Ag@SP-MSN exhibited better antibacterial activity against both E.coli and S.aureus than Ag@MSN under visible light illumination,indicating the efficient photo-responsive isomerization of spiropyran.Furthermore,the Ag@SP-MSN embedded gel demonstrated outstanding antifouling ability even after 21 days when compared to AgNPs gel.The long-term photo-controllable antifouling property proved the excellent reversible absorption and release of Ag@SP-MSN towards AgNPs.This work provides new insights into the safe utilization of nanomaterials,offering promising advancements to meet clinical antibacterial requirements.
基金supported in part by Beijing Nova Program of Science and Technology(20220484127)National Natural Science Foundation of China(82171818)。
文摘Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to humans.Despite the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global health.OPXV includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).
基金This study was supported by the Shenzhen Science and Technology Innovation Commission Basic Research Program[JCYJ20190807155409373]the Natural Science Foundation of China Excellent Young Scientists Fund[82022064]+6 种基金Natural Science Foundation of China International/Regional Research Collaboration Project[72061137001]the Sanming Project of Medicine in Shenzhen[SZSM201811071]the High Level Project of Medicine in Longhua,Shenzhen[HLPM201907020105]Special Support Plan for High-Level Talents of Guangdong Province[2019TQ05Y230]the Fundamental Research Funds for the Central Universities[58000-31620005]Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences[2020-JKCS-030]All funding parties did not have any role in the design of the study or in the explanation of the data.
文摘Background In 2003,China implemented free antiretroviral therapy(ART)for people living with HIV(PLHIV),establishing an eligibility threshold of CD4<200 cells/μl.Subsequently,the entry criteria were revised in 2012(eligibility threshold:CD4≤350 cells/μl),2014(CD4≤500 cells/μl),and 2016(treat-all).However,the impact of treat-all policy on HIV care and treatment indicators in China is unknown.We aimed to elucidate the immediate and long-term impact of the implementation of treat-all policy in China.Methods Anonymized programmatic data on ART initiation and collection in PLHIV who newly started ART were retrieved between 1 January 2015 and 31 December 2019,from two provincial and municipal Centers for Disease Control and Prevention and ten major infectious disease hospitals specialized in HIV care in China.We used Poisson and quasi-Poisson segmented regression models to estimate the immediate and long-term impact of treat-all on three key indicators:monthly proportion of 30-day ART initiation,mean CD4 counts(cells/μl)at ART initiation,and mean estimated time from infection to diagnosis(year).We built separate models according to gender,age,route of transmission and region.Results Monthly data on ART initiation and collection were available for 75,516 individuals[gender:83.8%males;age:median 39 years,interquartile range(IQR):28-53;region:18.5%Northern China,10.9%Northeastern China,17.5%Southern China,49.2%Southwestern China].In the first month of treat-all,compared with the contemporaneous counterfactual,there was a significant increase in proportion of 30-day ART initiation[+12.6%,incidence rate ratio(IRR)=1.126,95%CI:1.033-1.229;P=0.007]and mean estimated time from infection to diagnosis(+7.0%,IRR=1.070,95%CI:1.021-1.120;P=0.004),while there was no significant change in mean CD4 at ART initiation(IRR=0.990,95%CI:0.956-1.026;P=0.585).By December 2019,the three outcomes were not significantly different from expected levels.In the stratified analysis,compared with the contemporaneous counterfactual,mean CD4 at ART initiation showed significant increases in Northern China(+3.3%,IRR=1.033,95%CI:1.001-1.065;P=0.041)and Northeastern China(+8.0%,IRR=1.080,95%CI:1.003-1.164;P=0.042)in the first month of treat-all;mean estimated time from infection to diagnosis showed significant increases in male(+5.6%,IRR=1.056,95%CI:1.010-1.104;P=0.016),female(+14.8%,IRR=1.148,95%CI:1.062-1.240;P<0.001),aged 26-35(+5.3%,IRR=1.053,95%CI:1.001-1.109;P=0.048)and>50(+7.8%,IRR=1.078,95%CI:1.000-1.161;P=0.046),heterosexual transmission(+12.4%,IRR=1.124,95%CI:1.042-1.213;P=0.002)and Southwestern China(+12.9%,IRR=1.129,95%CI:1.055-1.208;P<0.001)in the first month of treat-all.Conclusions The implementation of treat-all policy in China was associated with a positive effect on HIV care and treatment outcomes.To advance the work of rapid ART,efforts should be made to streamline the testing and ART initiation process,provide comprehensive support services,and address the issue of uneven distribution of medical resources.
基金supported by the National Key R&D Program of China(Grant No.2020YFC1521605)the National Natural Science Foundation of China(Grant Nos.41971002,41971016.41671014 and U2039201)+3 种基金the National Social Science Foundation of China(Grant No.19ZDA227)the Study of Environment Archaeology in Zhengzhou,the Digital Environment Archaeology Specially-appointed Researcher of Henan,China(Grant No.210501002)the Science and Technology Open Cooperation Project(Grant No.210901006)the Science and Technology Think-Tank Project of Henan Academy of Sciences(Grant No.210701002)。
文摘The emergence of the"Ancient State"is considered an important stage in the discourse on human civilizations.Based on its complex and hierarchical social structure,the Shuanghuaishu site of Henan Province is regarded as an"Ancient state",specifically the"Heluo Ancient State".The site is situated in the middle reaches of the Yellow River region and played a key role in prehistoric China.However,the reasons behind its decline are unclear.Here,we conducted an integrated investigation of the archaeological excavations and archaeoseismic analyses at the Shuanghuaishu site.We identified paleoseismic remains within paleo-artificial moats,which were formed owing to off-fault structures of soil liquefaction,hillslope landslides,and related ground fractures,along with shake-related wall disruption and building collapse in the residential zone.Charcoal dating was conducted to constrain the age for this earthquake event,which was determined to be approximately 5.0 cal kyr BP.Furthermore,based on the practical curve for earthquake-induced liquefaction,the preliminary estimate of the magnitude of this paleo seismic event is greater than M_(s)5.9-6.0.We propose that the Shuanghuaishu site experienced a recession after the earthquake event,which may have influenced the continuous development of the"Heluo Ancient State"as a regional center settlement.
基金supported by the Natural Science Foundation of China(Nos.22125902,U2032202,21975243 and 21825302)the National Program for Support of Topnotch Young Professionals,the Fundamental Research Funds for the Central Universities(No.WK2030020032)+1 种基金the DNL cooperation Fund,CAS(No.DNL202020)the Anhui Science Fund for Distinguished Young Scholars(No.2208085J15).
文摘The undesirable shuttle effect and sluggish redox kinetics of polysulfides seriously result in low sulfur utilization and poor capacity retention.Here,an integrated strategy is proposed by rational designing multifunctional architecture to manipulate the redox kinetics of polysulfides,specifically,by employing iron atoms(Fe-As)and iron-species nanoparticles(Fe-NPs)co-embedded nitrogen-doped carbon nanotube(Fe-NCNT)as catalyst and host for sulfur.The synergistic cooperation of Fe-As and Fe-NPs provides efficient active sites to facilitate the diffusion,strengthen the affinities,and promote the conversion reactions for polysulfides.Furthermore,the NCNT not only offers practical Li+transport pathways but also immobilize the polysulfides effectively.Benefiting from these merits,the Fe-NCNT/S electrodes exhibit high initial specific capacity of 1502.6 mAh/g at 0.1 C,outstanding rate performance(830 mAh/g at 2 C),and good cycling performance(597.8 mAh/g after 500 cycles with an ultralow capacity fading rate of 0.069%per cycle).This work features the distinct interaction of iron atom-nanoparticles on facilitating immobilization-diffusion-transformation process of polysulfides,and it also expected to pave the way for the application in practical Li-S batteries.
基金Supported by National Natural Science Foundation of China(81872674),and Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(2022XM45).
文摘Summary What is already known about this topic?Although a third coronavirus disease 2019(COVID-19)vaccination(booster)dose is highly recommended for diabetic patients,the vaccination behaviors and related adverse events are unclear among diabetic patients with a COVID-19 booster dose.What is added by this report?Diabetic patients with higher postprandial blood glucose,worrying about the safety of the booster dose were less likely to get the vaccine.
基金This study was supported by the National Natural Science Foundation of China(81872674)the Joint Foundation of Innovative Environment Construction of Autonomous Region of Xinjiang(#2019D01C326)+2 种基金the Four“Batches”Innovation Project of Invigorating Medical Cause through Science and Technology of Shanxi Province(2022XM45)Shenzhen Science and Technology Innovation Committee Projects(No.JCYJ20220818102817038)the Scientific Research Foundation of Peking University Shenzhen Hospital(No.KYQD2022216).
文摘Summary What is already known about this topic?Cancer patients are more vulnerable and have higher mortality rates from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)than the general population;however,coverage for booster doses of the coronavirus disease 2019(COVID-19)vaccine was low among cancer patients in China.What is added by this report?Overall,32.0%and 56.4%of cancer patients from four Provincial Level Administrative Divisions(PLADs)expressed hesitancy toward the first and second booster doses,respectively.Factors negatively associated with hesitancy to receive booster doses included positive attitudes,perceived support,and higher exposure to COVID-19 vaccination information.Conversely,postvaccination fatigue was positively associated with vaccine hesitancy.What are the implications for public health practice?Improved COVID-19 vaccination coverage is needed to promote health for cancer patients.
基金partially funded by the Defense Industrial Technology Development Program JCKY2020802B001 and the National Natural Science Foundation of China 82041019.
文摘Aluminum(alum)adjuvant is the most extensively used protein subunit vaccine adjuvant,and its effectiveness and safety have been widely recognized.The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant,which directly affects the immune efficacy of the protein vaccine.In our study,we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptorbinding domain(RBD),achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant.
基金supported by the National Natural Science Foundation of China under Grant No.81772546(to X.C.),No.81827804(to X.C.)and No.81902367(to J.X.)Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ19H160026(to J.X.)and LGF18H160011(to Y.L.)+6 种基金China Postdoctoral Science Foundation under Grant No.2020M671755(to J.X.)Key Research and Development Project of Zhejiang Province under Grant No.2018C03083(to X.C.)Zhejiang Clinical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases under Grant No.2018E50003(to X.C.)Special fund for basic scientific research operating expenses of Zhejiang University under Grant No.2019XZZX005-4-05(to Y.L.)Hepatobiliary and Pancreatic Cancer Research of Hubei Chen Xiaoping Science and Technology Development Foundation under Grant No.CXPJJH11900001-2019308(to J.X.)CXPJJH11900001-2019209(to X.L.)CXPJJH11900009-03(to X.L.).
文摘Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully clarified.Here we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant HCC cells),plays a significant role in sorafenib resistance in HCC.We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib.Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation.Moreover,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells.Using different HCC mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance.Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.
基金supported by the National Natural Science Foundation of China(81702981,81827804,81902367,81772546and LQ18H160010)Zhejiang Provincial Natural Science Foundation of China(LY20H160021 and Y15H160052)+1 种基金China Postdoctoral Science Foundation(2020T130584 and 2020M671755)Health Innovation Talent Support Project of Zhejiang Medical and Health Science and Technology Plan(2021447581)。
文摘The treatment of hepatocellular carcinoma(HCC)has been dominated by multikinase inhibitors for more than a decade.However,drug resistance can severely restrict the efficacy of these drugs.Using CRISPR/CAS9 genome library screening,we evaluated Kelch-like ECH-associated protein 1(KEAP1)as a key regulator of sorafenib’s susceptibility in HCC.We also investigated whether KEAP1’s knockdown can stabilize nuclear factor(erythroid-derived 2)-like 2(NRF2)protein levels that led to sorafenib’s resistance,including an NRF2 inhibitor that can synergize with sorafenib to abolish HCC’s growth in vitro and in vivo.Furthermore,we clarified that fibroblast growth factor 21(FGF21)is an important downstream regulator of NRF2 in HCC.Intriguingly,we observed that FGF21 bound to NRF2 through the C-terminus of FGF21,thereby stabilizing NRF2 by reducing its ubiquitination and generating a positive feedback loop in sorafenib-resistant HCC.These findings,therefore,propose that targeting FGF21 is a promising strategy to combat HCC sorafenib’s resistance.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41673061, 41462001 & 41688103)the Chinese Academy of Sciences Instrument and Equipment Function Development Project (Grant No. IGG201803)。
文摘The placement of the Ediacaran-Cambrian boundary in deep-water realm in South China and the high-precision temporal framework for the Ediacaran-Cambrian transition in this region have not yet been completely solved. Recently, we have found two K-bentonite beds in the top of the Liuchapo Formation at the Pingyin section, Guizhou Province. It provides an opportunity for constructing the temporal framework of the transitional strata on the Yangtze Platform in South China and for determining the Ediacaran-Cambrian boundary in this area. In this study, we conducted high-precision CA-ID-TIMS U-Pb dating on zircons from the two K-bentonites. The ages of the two K-bentonites were precisely constrained at 536.40±0.47/1.1/1.2 Ma(2σ, n=7, MSWD=0.92) and 541.48±0.46/1.1/1.2 Ma(2σ, n=8, MSWD=1.3). Combining the geochronological results with organic carbon isotope data of chert in the topmost Liuchapo Formation from the section, we suggest that the EdiacaranCambrian boundary should be consistent with a significant negative organic carbon isotope excursion between the two Kbentonites. The scheme of the Ediacaran-Cambrian boundary in this study is of great significance for global correlation, and further for unravelling the information of the terminal Ediacaran-early Cambrian ocean.
基金We acknowledge the financial support from the National Key R&D Program of China(2016YFA0200102 and 2017YFA0206301)the National Natural Science Foundation of China(51631001,51590882,51672010 and 81421004).