Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated ...Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.展开更多
The mechanism of sphingosine-1-phosphate(S1P)-mediated phagocytosis remains unknown.Here,we found that S1P or FTY720(an analog of S1P)promoted microglial phagocytosis in stroke independent of S1PRs.First,we used compu...The mechanism of sphingosine-1-phosphate(S1P)-mediated phagocytosis remains unknown.Here,we found that S1P or FTY720(an analog of S1P)promoted microglial phagocytosis in stroke independent of S1PRs.First,we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2(TREM2).Next,microscale thermophoresis(MST),surface plasmon resonance(SPR)and liquid chromatography–tandem mass spectrometry(LC–MS/MS)were performed to reveal that S1P was a novel TREM2 ligand.Then,we confirmed the pro-phagocytosis of S1P targeting in Trem2-Dap12 transfected CHO cells and TREM2 knockdown microglia.Point mutation analysis showed that D104 was the critical binding residue.Trem2^(−/−)mice were used to demonstrate the role of S1P-induced phagocytosis targeting on TREM2 in protecting against ischemic brain injury.Finally,further studies revealed that apolipoprotein E(APOE)loaded with S1P was released by microglia and bound to apoptotic neurons via LDL receptor related protein 1B(LRP1B)and thereby induced microglia to phagocytose apoptotic neurons.Overall,the present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis.Our findings provide a new lead compound for developing immunomodulator targeting on TREM2.展开更多
Streptomycin(STR)plays an essential role in bacterial infection treatments.Selectivity and sensitivity of photoelectrochemical(PEC)sensors are the two most important parameters,which can be measured using the photosen...Streptomycin(STR)plays an essential role in bacterial infection treatments.Selectivity and sensitivity of photoelectrochemical(PEC)sensors are the two most important parameters,which can be measured using the photosensitivity of its active material.We prepared a novel PEC sensor to detect STR using Bi/BiVO4/LDH(layered double hydroxides)heterostructures as an active material,which is photoactive in the visible light wavelength range.The simultaneous presence of LDH and Bi/BiVO4 enhanced the material photocurrent response,which was linear to the STR concentrations in the 0.01–500 nmol/L range.The STR detection limit by this sensor was 0.0042 nmol/L.Our novel PEC-based sensing strategy includes using an ultra-sensitive and highly selective sensor for STR detection.Additionally,the two-pot synthesis of Bi/BiVO4/LDH developed in this work is environmentally friendly.展开更多
HNULP1,a new member of the basic helixloop-helix transcription factors,contains a DUF654 domain in its C-terminus and is highly conserved from Drosophilae,yeast,zebrafish to mouse.The function of this motif,however,is...HNULP1,a new member of the basic helixloop-helix transcription factors,contains a DUF654 domain in its C-terminus and is highly conserved from Drosophilae,yeast,zebrafish to mouse.The function of this motif,however,is currently unknown.In this research,we fused five deletion fragments of the DUF654 domain to the GAL4 DNA-binding domain and then co-transfected with plasmids L8G5-Luc and VP-16.The analysis of the GAL4 luciferase reporter gene indicated that fragments from 228 to 407 amino acids in the DUF654 domain had a strong transcription repression activity.Therefore,this study lays a solid foundation for research on the mechanism of hnulp1 transcriptional regulation and the function of the DUF654 domain.展开更多
Objective:This survey was designed to understand the misconceptions about labor epidurals.Methods:This voluntary and anonymous online survey on wenjuan.com was conducted from September 1st,2015 to January 1st,2016 via...Objective:This survey was designed to understand the misconceptions about labor epidurals.Methods:This voluntary and anonymous online survey on wenjuan.com was conducted from September 1st,2015 to January 1st,2016 via mainly WeChat groups dedicated to perinatal healthcare providers in China.The questionnaire included items inquiring the knowledge and opinions about labor epidural analgesia related to maternal complications,baby safety,and effect on laboring.Incomplete surveys were excluded from the data analysis.The data was presented as percentages and a Chi-square test or Fisher's exact test,as appreciate,was used to quantitatively compare the results.Results:A total of 1412 respondents completed surveys with 42.9%(606/1412)of them being anesthesiologists,35.1%(495/1412)being obstetricians,11.8%(167/1412)being midwives,3.7%(52/1412)being labor and delivery nurses,and 6.5%(92/1412)being hospital administrators and unspecified.The study revealed a lack of knowledge in labor pain control.Although 82.4%(1164/1412)of respondents were familiar with labor epidural analgesia,8.9%(126/1412)did not know how it works,and 1.1%(15/1412)never heard it in a multiple-choice question.The three main groups(anesthesiologists,obstetricians,and midwives/labor and delivery nurses)were chosen for comparisons.Opinions among these three groups concerning five questions in the three main concerns were evaluated using a statistical significance of P<0.05.Conclusion:The results in our survey indicated an urgent need of continuing medical education to multidisciplinary specialties to improve evidence-based medical practices as these misconceptions have existed for over 10 years in the medical professionals.Lack of public awareness fueled by misconceptions related to labor epidural analgesia may be associated with a lack of professional knowledge.Correct knowledge in professionals needs to be disseminated to the public in order to dispel possible misconceptions and rumors about labor epidural analgesia.This would not only enhance patient understanding of their care but also improve maternal,fetal,and neonatal outcomes.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 81503039)
文摘Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus,the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.
基金supported by the National Natural Science Foundation of China (Nos.81973301, 82003732 and 81773701)the Medical Research Project of Jiangsu Commission of Health (No.ZDA2020006, China)+3 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No.18KJA310004)the Major Project of Nanjing Medical University (No.NMUD2018008, China)the Postgraduate Research and Practice Innovation Program of Jiangsu Province (Nos.KYCX19_1121 and KYCX20_1417, China)Priority Academic Program Development of Jiangsu Higer Education Institutions (China)
文摘The mechanism of sphingosine-1-phosphate(S1P)-mediated phagocytosis remains unknown.Here,we found that S1P or FTY720(an analog of S1P)promoted microglial phagocytosis in stroke independent of S1PRs.First,we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2(TREM2).Next,microscale thermophoresis(MST),surface plasmon resonance(SPR)and liquid chromatography–tandem mass spectrometry(LC–MS/MS)were performed to reveal that S1P was a novel TREM2 ligand.Then,we confirmed the pro-phagocytosis of S1P targeting in Trem2-Dap12 transfected CHO cells and TREM2 knockdown microglia.Point mutation analysis showed that D104 was the critical binding residue.Trem2^(−/−)mice were used to demonstrate the role of S1P-induced phagocytosis targeting on TREM2 in protecting against ischemic brain injury.Finally,further studies revealed that apolipoprotein E(APOE)loaded with S1P was released by microglia and bound to apoptotic neurons via LDL receptor related protein 1B(LRP1B)and thereby induced microglia to phagocytose apoptotic neurons.Overall,the present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis.Our findings provide a new lead compound for developing immunomodulator targeting on TREM2.
基金supported by Key projects of science and technology research in Hebei Higher Education Institutions(Nos.ZD2018311,ZD2020417)Local science and technology development fund projects guided by the Central Government(No.206Z1402G)+1 种基金Science and Technology Research Project of Colleges and Universities in Hebei Province(No.BJ2019203)Xingtai Science and Technology Program(Nos.2018ZC031,2018ZC227,2019ZZ023,2019ZX07).
文摘Streptomycin(STR)plays an essential role in bacterial infection treatments.Selectivity and sensitivity of photoelectrochemical(PEC)sensors are the two most important parameters,which can be measured using the photosensitivity of its active material.We prepared a novel PEC sensor to detect STR using Bi/BiVO4/LDH(layered double hydroxides)heterostructures as an active material,which is photoactive in the visible light wavelength range.The simultaneous presence of LDH and Bi/BiVO4 enhanced the material photocurrent response,which was linear to the STR concentrations in the 0.01–500 nmol/L range.The STR detection limit by this sensor was 0.0042 nmol/L.Our novel PEC-based sensing strategy includes using an ultra-sensitive and highly selective sensor for STR detection.Additionally,the two-pot synthesis of Bi/BiVO4/LDH developed in this work is environmentally friendly.
基金supported in part by the National Natural Science Foundation of China (Grant Nos.90508004,30470867,30570934,30671054,30671053,30671171,30670274,30671137)Program for Changjiang Scholars and Innovative Research Team in University,China (No.IRT0445)+2 种基金National Basic Research Program of China (No.2005CB522505)New Century Excellent Talents in University (NCET-05-0713)Hunan Provincial Natural Science Foundation of China (No.05J2007,06JJ4120).
文摘HNULP1,a new member of the basic helixloop-helix transcription factors,contains a DUF654 domain in its C-terminus and is highly conserved from Drosophilae,yeast,zebrafish to mouse.The function of this motif,however,is currently unknown.In this research,we fused five deletion fragments of the DUF654 domain to the GAL4 DNA-binding domain and then co-transfected with plasmids L8G5-Luc and VP-16.The analysis of the GAL4 luciferase reporter gene indicated that fragments from 228 to 407 amino acids in the DUF654 domain had a strong transcription repression activity.Therefore,this study lays a solid foundation for research on the mechanism of hnulp1 transcriptional regulation and the function of the DUF654 domain.
文摘Objective:This survey was designed to understand the misconceptions about labor epidurals.Methods:This voluntary and anonymous online survey on wenjuan.com was conducted from September 1st,2015 to January 1st,2016 via mainly WeChat groups dedicated to perinatal healthcare providers in China.The questionnaire included items inquiring the knowledge and opinions about labor epidural analgesia related to maternal complications,baby safety,and effect on laboring.Incomplete surveys were excluded from the data analysis.The data was presented as percentages and a Chi-square test or Fisher's exact test,as appreciate,was used to quantitatively compare the results.Results:A total of 1412 respondents completed surveys with 42.9%(606/1412)of them being anesthesiologists,35.1%(495/1412)being obstetricians,11.8%(167/1412)being midwives,3.7%(52/1412)being labor and delivery nurses,and 6.5%(92/1412)being hospital administrators and unspecified.The study revealed a lack of knowledge in labor pain control.Although 82.4%(1164/1412)of respondents were familiar with labor epidural analgesia,8.9%(126/1412)did not know how it works,and 1.1%(15/1412)never heard it in a multiple-choice question.The three main groups(anesthesiologists,obstetricians,and midwives/labor and delivery nurses)were chosen for comparisons.Opinions among these three groups concerning five questions in the three main concerns were evaluated using a statistical significance of P<0.05.Conclusion:The results in our survey indicated an urgent need of continuing medical education to multidisciplinary specialties to improve evidence-based medical practices as these misconceptions have existed for over 10 years in the medical professionals.Lack of public awareness fueled by misconceptions related to labor epidural analgesia may be associated with a lack of professional knowledge.Correct knowledge in professionals needs to be disseminated to the public in order to dispel possible misconceptions and rumors about labor epidural analgesia.This would not only enhance patient understanding of their care but also improve maternal,fetal,and neonatal outcomes.
