Dear editor,Human-robot collaboration is a research topic that has numerous potential applications, such as in smart cities. An important safety consideration in human-robot collaboration is collision avoidance[1]. Ma...Dear editor,Human-robot collaboration is a research topic that has numerous potential applications, such as in smart cities. An important safety consideration in human-robot collaboration is collision avoidance[1]. Many studies have prioritized collision avoidance of the robot end-effector. However, multi-joint(whole-body) collision avoidance is also very important in complex working scenarios. Several studies have achieved multi-joint collision avoidance by estimating the distance between obstacles and control points placed on the robot body.展开更多
Acetaldehyde dehydrogenase 2(ALDH2)mutations are commonly found in a subgroup of the Asian population.However,the role of ALDH2 in septic acute respiratory distress syndrome(ARDS)remains unknown.Here,we showed that hu...Acetaldehyde dehydrogenase 2(ALDH2)mutations are commonly found in a subgroup of the Asian population.However,the role of ALDH2 in septic acute respiratory distress syndrome(ARDS)remains unknown.Here,we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS.Intriguingly,ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA(cfDNA)and myeloperoxidase(MPO)-DNA than ALDH2WT-ARDS patients.To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS,we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice.In clinically relevant mouse sepsis models,Aldh2-/-mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis,a specific process that releases neutrophil extracellular traps(NETs)from neutrophils.Furthermore,we discovered that NETosis strongly promoted endothelial destruction,accelerated vascular leakage,and exacerbated septic ARDS.At the molecular level,ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4(PAD4)to inhibit NETosis,which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP.Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis.Together,our data reveal a novel ALDH2-based protective mechanism against septic ARDS,and the activation of ALDH2 may be an effective treatment strategy for sepsis.展开更多
Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We...Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We comprehensively searched PubMed,Embase,Scopus,Web of Science,Cochrane Library,ClinicalTrials,and MedRxiv databases on April 26,2022.Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria.Notably,this is the first meta-analysis on COVID-19,taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation(PA)and intermediate-to-therapeutic anticoagulation(I-TA).Results:We included 11 randomized controlled trials(RCTs)and 36 cohort studies with 27,051 COVID-19 patients.By analyzing all the RCTs,there was no significant difference in mortality between the PA and I-TA groups,which was further confirmed by trial sequential analysis(TSA)(odds ratio[OR]:0.93;95%confidence interval[CI]:0.71–1.22;P=0.61;TSA adjusted CI:0.71–1.26).The rate of major bleeding was remarkably higher in the I-TA group than in the PA group,despite adjusting for TSA(OR:1.73;95%CI:1.15–2.60;P=0.009;TSA adjusted CI:1.09–2.58).RCTs have supported the beneficial effect of I-TA in reducing thrombotic events.After including all studies,mortality in the I-TA group was significantly higher than in the PA group(OR:1.38;95%CI:1.15–1.66;P=0.0005).The rate of major bleeding was similar to the analysis from RCTs(OR:2.24;95%CI:1.86–2.69;P<0.00001).There was no distinct difference in the rate of thrombotic events between the 2 regimen groups.In addition,in both critical and noncritical subgroups,I-TA failed to reduce mortality but increased major bleeding rate compared with PA,as shown in meta-analysis of all studies,as well as RCTs only.Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding(P=0.14,P=0.09,respectively).Conclusion:I-TA is not superior to PA for treating COVID-19 because it fails to lower the mortality rate but increases the major bleeding rate in both critical and noncritical patients.展开更多
Background:Energy metabolism disorders contribute to the development of sepsis.Carnitine is essential for fatty acid metabolism and energy production.Therefore,we aimed to explore whether there is a causal relationshi...Background:Energy metabolism disorders contribute to the development of sepsis.Carnitine is essential for fatty acid metabolism and energy production.Therefore,we aimed to explore whether there is a causal relationship between carnitine levels and sepsis.Methods:Two-sample Mendelian randomization(MR)analysis was performed.The single nucleotide polymorphisms(SNPs)of carnitine from the genome-wide association(GWAS)study were used as exposure instrumental variables,and the susceptibility and severity of sepsis in the UK Biobank were used as outcomes.The inverse-variance weighted(IVW),MR-Egger,and weighted median methods were used to evaluate the causal relationship between exposure and outcomes.Heterogeneity was assessed using IVW and MR-Egger’s and Cochran’s Q tests,and pleiotropy was tested using the MR-Egger intercept and MR-PRESSO.Results:Using the IVW method,a one-standard-deviation increase in genetically determined carnitine levels was found to be associated with increased susceptibility to sepsis in populations under 75 years of age(odds ratio[OR]:2.696;95%confidence interval[CI]:1.127–6.452;P=0.026)and increased severity of sepsis(OR:22.31;95%CI:1.769–281.282;P=0.016).Sensitivity analysis did not re-veal heterogeneity or horizontal pleiotropy;therefore,the results indicated robustness.Conclusion:Genetic susceptibility to increased carnitine levels in the blood may increase the susceptibility and severity of sepsis.There-fore,interventions at an early stage in patients with high carnitine levels may reduce the risk of developing sepsis.展开更多
基金supported in part by the National Key Research and Development Program of China(2018YFB1305300)the China Postdoctoral Science Foundation(2020TQ0039,2021M700425)the National Natural Science Foundation of China(61733001,62103054,U2013602,61873039,U1913211,U1713215)。
文摘Dear editor,Human-robot collaboration is a research topic that has numerous potential applications, such as in smart cities. An important safety consideration in human-robot collaboration is collision avoidance[1]. Many studies have prioritized collision avoidance of the robot end-effector. However, multi-joint(whole-body) collision avoidance is also very important in complex working scenarios. Several studies have achieved multi-joint collision avoidance by estimating the distance between obstacles and control points placed on the robot body.
基金supported by the State Key Program of the National Natural Science Foundation of China(82030059)the National Science Fund for Distinguished Young Scholars(82325031)+7 种基金the National Natural Science Regional Innovation Fund Joint Fund Key Support Projects(U23A20485)the National Natural Science Foundation of China(82072144,82172127)the National Key R&D Program of China(2020YFC1512700,2020YFC1512705,2020YFC1512703)the Key R&D Program of Shandong Province(2021ZLGX02,2021SFGC0503,2022ZLGX03)the Taishan Pandeng Scholar Program of Shandong Province(tspd20181220)the Taishan Young Scholar Program of Shandong Province(tsqn202211312)the Clinical Research Project of Shandong University(2021SDUCRCC006)the Interdisciplinary Young Researcher Groups Program of Shandong University(2020QNQT004).
文摘Acetaldehyde dehydrogenase 2(ALDH2)mutations are commonly found in a subgroup of the Asian population.However,the role of ALDH2 in septic acute respiratory distress syndrome(ARDS)remains unknown.Here,we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS.Intriguingly,ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA(cfDNA)and myeloperoxidase(MPO)-DNA than ALDH2WT-ARDS patients.To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS,we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice.In clinically relevant mouse sepsis models,Aldh2-/-mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis,a specific process that releases neutrophil extracellular traps(NETs)from neutrophils.Furthermore,we discovered that NETosis strongly promoted endothelial destruction,accelerated vascular leakage,and exacerbated septic ARDS.At the molecular level,ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4(PAD4)to inhibit NETosis,which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP.Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis.Together,our data reveal a novel ALDH2-based protective mechanism against septic ARDS,and the activation of ALDH2 may be an effective treatment strategy for sepsis.
基金supported by the National Key R&D Program of China(2020YFC0846600,2020YFC1512700,2020YFC1512705,2020YFC1512703)National S&T Fundamental Resources Investigation Project(2018FY100600,2018FY100602)+2 种基金Taishan Pandeng Scholar Program of Shandong Province(tspd20181220)Taishan Young Scholar Program of Shandong Province(tsqn20161065,tsqn201812129)Youth Top-Talent Project of National Ten Thousand Talents Plan,and Qilu Young Scholar Program.
文摘Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We comprehensively searched PubMed,Embase,Scopus,Web of Science,Cochrane Library,ClinicalTrials,and MedRxiv databases on April 26,2022.Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria.Notably,this is the first meta-analysis on COVID-19,taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation(PA)and intermediate-to-therapeutic anticoagulation(I-TA).Results:We included 11 randomized controlled trials(RCTs)and 36 cohort studies with 27,051 COVID-19 patients.By analyzing all the RCTs,there was no significant difference in mortality between the PA and I-TA groups,which was further confirmed by trial sequential analysis(TSA)(odds ratio[OR]:0.93;95%confidence interval[CI]:0.71–1.22;P=0.61;TSA adjusted CI:0.71–1.26).The rate of major bleeding was remarkably higher in the I-TA group than in the PA group,despite adjusting for TSA(OR:1.73;95%CI:1.15–2.60;P=0.009;TSA adjusted CI:1.09–2.58).RCTs have supported the beneficial effect of I-TA in reducing thrombotic events.After including all studies,mortality in the I-TA group was significantly higher than in the PA group(OR:1.38;95%CI:1.15–1.66;P=0.0005).The rate of major bleeding was similar to the analysis from RCTs(OR:2.24;95%CI:1.86–2.69;P<0.00001).There was no distinct difference in the rate of thrombotic events between the 2 regimen groups.In addition,in both critical and noncritical subgroups,I-TA failed to reduce mortality but increased major bleeding rate compared with PA,as shown in meta-analysis of all studies,as well as RCTs only.Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding(P=0.14,P=0.09,respectively).Conclusion:I-TA is not superior to PA for treating COVID-19 because it fails to lower the mortality rate but increases the major bleeding rate in both critical and noncritical patients.
基金This study was supported by the State Key Program of the National Natural Science Foundation of China(82030059)National Natural Science Foundation of China(82172127,81772036,82072144,81671952,81873950,and 81873953)+4 种基金National Key R&D Program of China(2020YFC1512700,2020YFC1512705,2020YFC1512703,and 2020YFC0846600)National S&T Fundamental Resources Investigation Project(2018FY100600,2018FY100602)Taishan Pandeng Scholar Program of Shandong Province(tspd20181220)Taishan Young Scholar Program of Shandong Province(tsqn20161065,tsqn201812129)Youth Top-Talent Project of National Ten Thousand Talents Plan,Qilu Young Scholar Program,and the Fun-damental Research Funds of Shandong University(2018JC011).
文摘Background:Energy metabolism disorders contribute to the development of sepsis.Carnitine is essential for fatty acid metabolism and energy production.Therefore,we aimed to explore whether there is a causal relationship between carnitine levels and sepsis.Methods:Two-sample Mendelian randomization(MR)analysis was performed.The single nucleotide polymorphisms(SNPs)of carnitine from the genome-wide association(GWAS)study were used as exposure instrumental variables,and the susceptibility and severity of sepsis in the UK Biobank were used as outcomes.The inverse-variance weighted(IVW),MR-Egger,and weighted median methods were used to evaluate the causal relationship between exposure and outcomes.Heterogeneity was assessed using IVW and MR-Egger’s and Cochran’s Q tests,and pleiotropy was tested using the MR-Egger intercept and MR-PRESSO.Results:Using the IVW method,a one-standard-deviation increase in genetically determined carnitine levels was found to be associated with increased susceptibility to sepsis in populations under 75 years of age(odds ratio[OR]:2.696;95%confidence interval[CI]:1.127–6.452;P=0.026)and increased severity of sepsis(OR:22.31;95%CI:1.769–281.282;P=0.016).Sensitivity analysis did not re-veal heterogeneity or horizontal pleiotropy;therefore,the results indicated robustness.Conclusion:Genetic susceptibility to increased carnitine levels in the blood may increase the susceptibility and severity of sepsis.There-fore,interventions at an early stage in patients with high carnitine levels may reduce the risk of developing sepsis.
