杂原子掺杂可以调节电子结构以调整中间体吸附并优化反应路径,是设计高效CO_(2)还原反应(CO_(2)RR)催化剂的有应用前景的方法.B原子是常用的掺杂剂,引入B原子可以有效打破*COOH和OCHO*中间体的吉布斯自由能线性关系,并且可以通过与CO_(2...杂原子掺杂可以调节电子结构以调整中间体吸附并优化反应路径,是设计高效CO_(2)还原反应(CO_(2)RR)催化剂的有应用前景的方法.B原子是常用的掺杂剂,引入B原子可以有效打破*COOH和OCHO*中间体的吉布斯自由能线性关系,并且可以通过与CO_(2)中O原子结合来增强CO_(2)吸附能力.B掺杂碳材料、单金属和金属氧化物的研究结果表明,B原子掺杂催化剂的CO_(2)RR活性和/或选择性有明显提高,然而多数报道的单个活性位点的B掺杂催化剂仅表现出在相对狭窄的电位范围内的CO_(2)RR高性能,设计制备CO_(2)RR的宽电位高选择性催化剂仍是巨大挑战.研究表明,合金化是提供多种类的活性位点相互协调和增强催化剂固有活性,进而改善CO_(2)RR性能并调节产物分布的可行策略.引入B原子到合金中以调节电子结构,最终优化关键中间体吸附的活性位点,对于寻找具有宽电位窗口的先进催化剂具有重要意义.本文提出了一种通过B掺杂调节CuIn合金电子结构以实现宽电位高选择性的电子工程策略.所制得的B掺杂CuIn合金(CuIn(B))在–0.6 V(vs.RHE)时表现出99%的CO法拉第效率(FECO),并在一个宽的阴极电化学窗口(400 m V)内保持了超过90%的较高FECO.同时,采用X射线光电子能谱(XPS)和CO_(2)吸附实验等手段研究了CuIn(B)性能提升的原因,结果表明,B原子与CuIn之间存在强烈的相互作用,改变了CuIn的电子结构.CO_(2)吸附结果表明,CuIn(B)比CuIn拥有更强的CO_(2)吸附能力,证明它具有潜在的快速CO_(2)RR反应动力学.进一步通过密度泛函理论(DFT)模拟研究了催化剂的热力学反应能量学以揭示CO_(2)RR机制,结果表明,*COOH更倾向于在CuIn(B)上形成,且*CO与CuIn(B)催化位点的结合强度最佳,更利于CO_(2)还原反应为CO,而CuIn更利于作为HER的活性位点;决速步骤是*CO中间体向CO转移,以实现高CO选择性;热力学限制电位研究表明,CuIn(B)大大提高了CO_(2)到CO转化的选择性.随后通过差分电荷密度研究也进一步证明了电荷转移过程是从CuIn位点到B位点.此外,根据d带理论,催化剂中Cu和In原子的投影态密度和d带中心(Ed)研究进一步证明了催化剂结构中的电子价态的变化,与XPS结果相符;引入B可以优化催化剂的电子结构,从而调节催化剂和中间体之间的结合能力,实现了CO_(2)RR在宽电位范围内的高活性和选择性.综上,本文对于电化学CO_(2)RR机理的基础理解和其实际应用具有促进作用.展开更多
Urban drainage systems in coastal cities in SE China are characterized by often complex canal and sluicegate systems that are designed to safely drain pluvial flooding whilst preventing tidal inundation.However, the r...Urban drainage systems in coastal cities in SE China are characterized by often complex canal and sluicegate systems that are designed to safely drain pluvial flooding whilst preventing tidal inundation.However, the risk of coastal flooding in the region is expected to increase over the next 50-100 years, as urban areas continue to expand and sea-levels are expected to rise. To assess the impact of projected sealevel rise on this type of urban drainage system, a one-dimensional model and decision support tool was developed. The model indicated that although sea-level rise represents a significant challenge, flood probability will continue to be most influenced by rainfall. Events that are significant enough to cause flooding will most likely be minimally impacted by changes to the tidal frame. However, it was found that a sea-level rise of up to 1.2 m by 2010 would result in increased drainage times and higher volumes of over-topping when flooding occurs.展开更多
Background: To identify PTEN isoform and explore its potential role in tumor suppression. Methods: Western blotting, over-expression, shRNA mediated knocking-down, and bioinformatic analysis were used to identify PT...Background: To identify PTEN isoform and explore its potential role in tumor suppression. Methods: Western blotting, over-expression, shRNA mediated knocking-down, and bioinformatic analysis were used to identify PTEN isoform and test its effect on PI3K-Akt signaling pathway. Cell proliferation, apoptosis, and migration assays were used to test PTEN isoform's biological activities. Results: The PTEN isoform is about 15 kDa bigger than PTEN and its expression is dependent on PTEN status. Immunoprecipitation for PTEN isoform followed by screening with antibodies against ISG15, SUMO1/2/3, Ubiquitin, and Nedd8 showed the identified PTEN isoform is not a general proteinaceous post-translational modification. In addition, overexpression of PTEN cDNA in cells did not generate PTEN isoform whereas knocking-down of PTEN reduced the protein levels of both PTEN and PTEN isoform in a proportional manner. Analysis of PTEN DNA sequence disclosed an alternative translational starting code (CTG) upstream of canonical PTEN coding sequence. Expression of cloned PTEN isoform generated a protein with a size about 15 kDa bigger than PTEN and suppressed PI3K-Akt signaling pathway in cells. Overexpression of PTEN isoform also led to decrease in cell growth and enhanced serum starvation--and UV irradiation--induced apoptosis through activation of Caspase 3. Finally, expression of PTEN isoform inhibited cell migration in scratch assay. Conclusions: PTEN isoform has PTEN-Iike activity and might be a new tumor suppressor.展开更多
Unpredictable and irreproducible digital keys are required to modulate security-related information in secure communication systems.True random number generators(TRNGs)rather than pseudorandom number generators(PRNGs)...Unpredictable and irreproducible digital keys are required to modulate security-related information in secure communication systems.True random number generators(TRNGs)rather than pseudorandom number generators(PRNGs)are required for the highest level of security.TRNG is a significant component in the digital security realm for extracting unpredictable binary bitstreams.Presently,most TRNGs extract high-quality“noise”from unpredictable physical random phenomena.Thus,these applications must be equipped with external hardware for collecting entropy and converting them into a random digital sequence.This study introduces a lightweight and efficient true random number generator(LETRNG)that uses the inherent randomness of a central processing unit(CPU)and an operating system(OS)as the source of entropy.We then utilize a lightweight post-processing method based on XOR and fair coin operation to generate an unbiased random binary sequence.Evaluations based on two famous test suites(NIST and ENT)show that LETRNG is perfectly capable of generating high-quality random numbers suitable for various GNU/Linux systems.展开更多
Roadside green swales have emerged as popular stormwater management infrastructure in urban areas,serving to mitigate stormwater pollution and reduce urban surface water discharge.However,there is a limited understand...Roadside green swales have emerged as popular stormwater management infrastructure in urban areas,serving to mitigate stormwater pollution and reduce urban surface water discharge.However,there is a limited understanding of the various types,structures,and functions of swales,as well as the potential challenges they may face in the future.In recent years,China has witnessed a surge in the adoption of roadside green swales,especially as part of the prestigious Sponge City Program(SCP).These green swales play a crucial role in controlling stormwater pollution and conserving urban water resources by effectively removing runoff pollutants,including suspended solids,nitrogen,and phosphorus.This review critically examines recent research findings,identifies key knowledge gaps,and presents future recommendations for designing green swales for effective stormwater management,with a particular emphasis on ongoing major Chinese infrastructure projects.Despite the growing global interest in bioswales and their significance in urban development,China's current classification of such features lacks a clear definition or specific consideration of bioswales.Furthermore,policymakers have often underestimated the adverse environmental effects of road networks,as reflected in existing laws and planning documents.This review argues that the construction and maintenance of roadside green swales should be primarily based on three critical factors:Wellthought-out road planning,suitable construction conditions,and sustainable long-term funding.The integration of quantitative environmental standards into road planning is essential to effectively address the challenge of pollution from rainfall runoff.To combat pollution associated with roads,a comprehensive assessment of potential pollution loadings should be carried out,guiding the appropriate design and construction of green swales,with a particular focus on addressing the phenomenon of first flush.One of the major challenges faced in sustaining funds for ongoing maintenance after swale construction.To address this issue,the implementation of a green finance platform is proposed.Such a platform would help ensure the availability of funds for continuous maintenance,thus maximizing the long-term effectiveness of green swales in stormwater management.Ultimately,the findings of this review aim to assist municipal governments in enhancing and implementing future urban road designs and SCP developments,incorporating effective green swale strategies.展开更多
Circulating tumor cells(CTCs)are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood.Understanding of the metastatic cascade of CTCs has tremendous potential for the id...Circulating tumor cells(CTCs)are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood.Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis.Detecting these very rare CTCs among the massive blood cells is challenging.However,emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application.Current technologies for the detection of CTCs are summarized herein,together with their advantages and disadvantages.The detection of CTCs is usually dependent on molecular markers,with the epithelial cell adhesion molecule being the most widely used,although molecular markers vary between different types of cancer.Properties associated with epithelial-tomesenchymal transition and stemness have been identified in CTCs,indicating their increased metastatic capacity.Only a small proportion of CTCs can survive and eventually initiate metastases,suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis.Single-cell sequencing of CTCs has been extensively investigated,and has enabled researchers to reveal the genome and transcriptome of CTCs.Herein,we also review the clinical applications of CTCs,especially for monitoring response to cancer treatment and in evaluating prognosis.Hence,CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.展开更多
Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic alterations.These aging-associated epigenetic changes include DNA methylation,histone mo...Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic alterations.These aging-associated epigenetic changes include DNA methylation,histone modification,chromatin remodeling,non-coding RNA(ncRNA)regulation,and RNA modification,all of which participate in the regulation of the aging process,and hence contribute to aging-related diseases.Therefore,understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging.Indeed,aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models.Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions.In addition,adopting health-promoting activities,such as caloric restriction,exercise,and calibrating circadian rhythm,has been demonstrated to delay aging.Furthermore,various clinical trials for aging intervention are ongoing,providing more evidence of the safety and efficacy of these therapies.Here,we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.展开更多
Background:The coronavirus disease 2019(COVID-19)is an ongoing pandemic.Invasive mechanical ventilation(IMV)is essential for the management of COVID-19 with acute respiratory distress syndrome(ARDS).We aimed to assess...Background:The coronavirus disease 2019(COVID-19)is an ongoing pandemic.Invasive mechanical ventilation(IMV)is essential for the management of COVID-19 with acute respiratory distress syndrome(ARDS).We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV.Methods:In this retrospective,single-center,case series study,patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University,China,from January 8th,2020,to March 24th,2020,with the final follow-up date of April 20th,2020,were included.Demographic,clinical,laboratory,imaging,and management information were collected and analyzed.Compliance with the respiratory support decision system was documented,and its relationship with 28-day mortality was evaluated.Results:The study included 46 COVID-19-associated ARDS patients who required IMV.The median age of the 46 patients was 68.5 years,and 31 were men.The partial pressure of arterial oxygen(PaO_(2))/fraction of inspired oxygen(FiO_(2))ratio at intensive care unit(ICU)admission was 104 mmHg.The median total length of IMV was 12.0(interquartile range[IQR]:6.0–27.3)days,and the median respiratory support decision score was 11.0(IQR:7.8–16.0).To 28 days after ICU admission,18(39.1%)patients died.Survivors had a significantly higher respiratory support decision score than non-survivors(15.0[10.3–17.0]vs.8.5(6.0–10.3),P=0.001).Using receiver operating characteristic(ROC)curve to assess the discrimination of respiratory support decision score to 28-day mortality,the area under the curve(AUC)was 0.796(95%confidence interval[CI]:0.657–0.934,P=0.001)and the cut-offwas 11.5(sensitivity=0.679,specificity=0.889).Patients with a higher score(>11.5)were more likely to survive at 28 days after ICU admission(log-rank test,P<0.001).Conclusions:For severe COVID-19-associated ARDS with IMV,following the respiratory support decision and assessing completion would improve the progress of ventilation.With a decision score of>11.5,the mortality at 28 days after ICU admission showed an obvious decrease.展开更多
文摘杂原子掺杂可以调节电子结构以调整中间体吸附并优化反应路径,是设计高效CO_(2)还原反应(CO_(2)RR)催化剂的有应用前景的方法.B原子是常用的掺杂剂,引入B原子可以有效打破*COOH和OCHO*中间体的吉布斯自由能线性关系,并且可以通过与CO_(2)中O原子结合来增强CO_(2)吸附能力.B掺杂碳材料、单金属和金属氧化物的研究结果表明,B原子掺杂催化剂的CO_(2)RR活性和/或选择性有明显提高,然而多数报道的单个活性位点的B掺杂催化剂仅表现出在相对狭窄的电位范围内的CO_(2)RR高性能,设计制备CO_(2)RR的宽电位高选择性催化剂仍是巨大挑战.研究表明,合金化是提供多种类的活性位点相互协调和增强催化剂固有活性,进而改善CO_(2)RR性能并调节产物分布的可行策略.引入B原子到合金中以调节电子结构,最终优化关键中间体吸附的活性位点,对于寻找具有宽电位窗口的先进催化剂具有重要意义.本文提出了一种通过B掺杂调节CuIn合金电子结构以实现宽电位高选择性的电子工程策略.所制得的B掺杂CuIn合金(CuIn(B))在–0.6 V(vs.RHE)时表现出99%的CO法拉第效率(FECO),并在一个宽的阴极电化学窗口(400 m V)内保持了超过90%的较高FECO.同时,采用X射线光电子能谱(XPS)和CO_(2)吸附实验等手段研究了CuIn(B)性能提升的原因,结果表明,B原子与CuIn之间存在强烈的相互作用,改变了CuIn的电子结构.CO_(2)吸附结果表明,CuIn(B)比CuIn拥有更强的CO_(2)吸附能力,证明它具有潜在的快速CO_(2)RR反应动力学.进一步通过密度泛函理论(DFT)模拟研究了催化剂的热力学反应能量学以揭示CO_(2)RR机制,结果表明,*COOH更倾向于在CuIn(B)上形成,且*CO与CuIn(B)催化位点的结合强度最佳,更利于CO_(2)还原反应为CO,而CuIn更利于作为HER的活性位点;决速步骤是*CO中间体向CO转移,以实现高CO选择性;热力学限制电位研究表明,CuIn(B)大大提高了CO_(2)到CO转化的选择性.随后通过差分电荷密度研究也进一步证明了电荷转移过程是从CuIn位点到B位点.此外,根据d带理论,催化剂中Cu和In原子的投影态密度和d带中心(Ed)研究进一步证明了催化剂结构中的电子价态的变化,与XPS结果相符;引入B可以优化催化剂的电子结构,从而调节催化剂和中间体之间的结合能力,实现了CO_(2)RR在宽电位范围内的高活性和选择性.综上,本文对于电化学CO_(2)RR机理的基础理解和其实际应用具有促进作用.
基金supported by funding from the Ningbo Social Development Project, Ningbo Science and Technology Bureau,China (Grant No. 2014C50011)
文摘Urban drainage systems in coastal cities in SE China are characterized by often complex canal and sluicegate systems that are designed to safely drain pluvial flooding whilst preventing tidal inundation.However, the risk of coastal flooding in the region is expected to increase over the next 50-100 years, as urban areas continue to expand and sea-levels are expected to rise. To assess the impact of projected sealevel rise on this type of urban drainage system, a one-dimensional model and decision support tool was developed. The model indicated that although sea-level rise represents a significant challenge, flood probability will continue to be most influenced by rainfall. Events that are significant enough to cause flooding will most likely be minimally impacted by changes to the tidal frame. However, it was found that a sea-level rise of up to 1.2 m by 2010 would result in increased drainage times and higher volumes of over-topping when flooding occurs.
基金Advanced key Scientific and Technological Programs of Ningbo(2013C51009)National Natural Science Foundation of China(31271451)
文摘Background: To identify PTEN isoform and explore its potential role in tumor suppression. Methods: Western blotting, over-expression, shRNA mediated knocking-down, and bioinformatic analysis were used to identify PTEN isoform and test its effect on PI3K-Akt signaling pathway. Cell proliferation, apoptosis, and migration assays were used to test PTEN isoform's biological activities. Results: The PTEN isoform is about 15 kDa bigger than PTEN and its expression is dependent on PTEN status. Immunoprecipitation for PTEN isoform followed by screening with antibodies against ISG15, SUMO1/2/3, Ubiquitin, and Nedd8 showed the identified PTEN isoform is not a general proteinaceous post-translational modification. In addition, overexpression of PTEN cDNA in cells did not generate PTEN isoform whereas knocking-down of PTEN reduced the protein levels of both PTEN and PTEN isoform in a proportional manner. Analysis of PTEN DNA sequence disclosed an alternative translational starting code (CTG) upstream of canonical PTEN coding sequence. Expression of cloned PTEN isoform generated a protein with a size about 15 kDa bigger than PTEN and suppressed PI3K-Akt signaling pathway in cells. Overexpression of PTEN isoform also led to decrease in cell growth and enhanced serum starvation--and UV irradiation--induced apoptosis through activation of Caspase 3. Finally, expression of PTEN isoform inhibited cell migration in scratch assay. Conclusions: PTEN isoform has PTEN-Iike activity and might be a new tumor suppressor.
基金This work was partially supported by National Key R&D Program of China(No.2020YFC0832500)Fundamental Research Funds for the Central Universities(Nos.lzujbky-2021-sp47,lzujbky-2020-sp02,lzujbky-2019-kb51,and lzujbky2018-k12)the National Natural Science Foundation of China(No.61402210).We also gratefully acknowledge the support of NVIDIA Corporation with the donation of the Jetson-TX1 used for this research.
文摘Unpredictable and irreproducible digital keys are required to modulate security-related information in secure communication systems.True random number generators(TRNGs)rather than pseudorandom number generators(PRNGs)are required for the highest level of security.TRNG is a significant component in the digital security realm for extracting unpredictable binary bitstreams.Presently,most TRNGs extract high-quality“noise”from unpredictable physical random phenomena.Thus,these applications must be equipped with external hardware for collecting entropy and converting them into a random digital sequence.This study introduces a lightweight and efficient true random number generator(LETRNG)that uses the inherent randomness of a central processing unit(CPU)and an operating system(OS)as the source of entropy.We then utilize a lightweight post-processing method based on XOR and fair coin operation to generate an unbiased random binary sequence.Evaluations based on two famous test suites(NIST and ENT)show that LETRNG is perfectly capable of generating high-quality random numbers suitable for various GNU/Linux systems.
基金the National Key R&D Program of China(Grant Nos.2021YFE0193100 and 2019YFC1510400)the Construction Project of China Knowledge Centre for Engineering Sciences and Technology(Grant No.CKCEST-2022-1-41)+1 种基金the National Natural Science Foundation Program of China(Grant No.NSFC41850410497)the Institute of Asia Pacific Studies(IAPS)research funds and the Doctoral Training Partnership and the postgraduate research fund at University Nottingham Ningbo China and the Institute of Urban Environment,Chinese Academy of Sciences.
文摘Roadside green swales have emerged as popular stormwater management infrastructure in urban areas,serving to mitigate stormwater pollution and reduce urban surface water discharge.However,there is a limited understanding of the various types,structures,and functions of swales,as well as the potential challenges they may face in the future.In recent years,China has witnessed a surge in the adoption of roadside green swales,especially as part of the prestigious Sponge City Program(SCP).These green swales play a crucial role in controlling stormwater pollution and conserving urban water resources by effectively removing runoff pollutants,including suspended solids,nitrogen,and phosphorus.This review critically examines recent research findings,identifies key knowledge gaps,and presents future recommendations for designing green swales for effective stormwater management,with a particular emphasis on ongoing major Chinese infrastructure projects.Despite the growing global interest in bioswales and their significance in urban development,China's current classification of such features lacks a clear definition or specific consideration of bioswales.Furthermore,policymakers have often underestimated the adverse environmental effects of road networks,as reflected in existing laws and planning documents.This review argues that the construction and maintenance of roadside green swales should be primarily based on three critical factors:Wellthought-out road planning,suitable construction conditions,and sustainable long-term funding.The integration of quantitative environmental standards into road planning is essential to effectively address the challenge of pollution from rainfall runoff.To combat pollution associated with roads,a comprehensive assessment of potential pollution loadings should be carried out,guiding the appropriate design and construction of green swales,with a particular focus on addressing the phenomenon of first flush.One of the major challenges faced in sustaining funds for ongoing maintenance after swale construction.To address this issue,the implementation of a green finance platform is proposed.Such a platform would help ensure the availability of funds for continuous maintenance,thus maximizing the long-term effectiveness of green swales in stormwater management.Ultimately,the findings of this review aim to assist municipal governments in enhancing and implementing future urban road designs and SCP developments,incorporating effective green swale strategies.
基金This study was supported by the funding of the National Natural Science Foundation of China(Grant No.82172344,81702866,Jiaojiao Zhou)Natural Science Foundation of Zhejiang Province(Grant No.LY21H160039,Jiaojiao Zhou)+1 种基金Fundamental Research Funds for the Central Universities(Grant No.2021FZJD009,Jiaojiao Zhou)the National Natural Science Foundation of China(Grant No.82072900,Yiding Chen).
文摘Circulating tumor cells(CTCs)are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood.Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis.Detecting these very rare CTCs among the massive blood cells is challenging.However,emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application.Current technologies for the detection of CTCs are summarized herein,together with their advantages and disadvantages.The detection of CTCs is usually dependent on molecular markers,with the epithelial cell adhesion molecule being the most widely used,although molecular markers vary between different types of cancer.Properties associated with epithelial-tomesenchymal transition and stemness have been identified in CTCs,indicating their increased metastatic capacity.Only a small proportion of CTCs can survive and eventually initiate metastases,suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis.Single-cell sequencing of CTCs has been extensively investigated,and has enabled researchers to reveal the genome and transcriptome of CTCs.Herein,we also review the clinical applications of CTCs,especially for monitoring response to cancer treatment and in evaluating prognosis.Hence,CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
基金National Key Research and Development Program of China(2020YFA0804000)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010000)+5 种基金CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)National Natural Science Foundation of China(81921006,92149301,92168201,92049116,32121001,82100140,31970597)National Key Research and Development Program of China(2020YFA08034012019YFA0802202)Program of the Beijing Natural Science Foundation(Z190019)Tencent Foundation(2021–1045),K.C.Wong Education Foundation(GJTD-2019-08),Youth Innovation Promotion Association of CAS(E1CAZW0401)Science&Technology Innovation 2030 of The Ministry of Science and Technology of China(2022ZD0214200).
文摘Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks,including genetic and epigenetic alterations.These aging-associated epigenetic changes include DNA methylation,histone modification,chromatin remodeling,non-coding RNA(ncRNA)regulation,and RNA modification,all of which participate in the regulation of the aging process,and hence contribute to aging-related diseases.Therefore,understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging.Indeed,aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models.Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions.In addition,adopting health-promoting activities,such as caloric restriction,exercise,and calibrating circadian rhythm,has been demonstrated to delay aging.Furthermore,various clinical trials for aging intervention are ongoing,providing more evidence of the safety and efficacy of these therapies.Here,we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases.A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.
基金supported by the Chinese Medical Information and Big Data Association(Bo Hu,No.Z-2019-1-003)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(Bo Hu,No.ZNJC202011)the key project of the Ministry of Science and Technology of China(Zhiyong Peng,No.2020YFC0841300).
文摘Background:The coronavirus disease 2019(COVID-19)is an ongoing pandemic.Invasive mechanical ventilation(IMV)is essential for the management of COVID-19 with acute respiratory distress syndrome(ARDS).We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV.Methods:In this retrospective,single-center,case series study,patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University,China,from January 8th,2020,to March 24th,2020,with the final follow-up date of April 20th,2020,were included.Demographic,clinical,laboratory,imaging,and management information were collected and analyzed.Compliance with the respiratory support decision system was documented,and its relationship with 28-day mortality was evaluated.Results:The study included 46 COVID-19-associated ARDS patients who required IMV.The median age of the 46 patients was 68.5 years,and 31 were men.The partial pressure of arterial oxygen(PaO_(2))/fraction of inspired oxygen(FiO_(2))ratio at intensive care unit(ICU)admission was 104 mmHg.The median total length of IMV was 12.0(interquartile range[IQR]:6.0–27.3)days,and the median respiratory support decision score was 11.0(IQR:7.8–16.0).To 28 days after ICU admission,18(39.1%)patients died.Survivors had a significantly higher respiratory support decision score than non-survivors(15.0[10.3–17.0]vs.8.5(6.0–10.3),P=0.001).Using receiver operating characteristic(ROC)curve to assess the discrimination of respiratory support decision score to 28-day mortality,the area under the curve(AUC)was 0.796(95%confidence interval[CI]:0.657–0.934,P=0.001)and the cut-offwas 11.5(sensitivity=0.679,specificity=0.889).Patients with a higher score(>11.5)were more likely to survive at 28 days after ICU admission(log-rank test,P<0.001).Conclusions:For severe COVID-19-associated ARDS with IMV,following the respiratory support decision and assessing completion would improve the progress of ventilation.With a decision score of>11.5,the mortality at 28 days after ICU admission showed an obvious decrease.