Humic substances(HS),which are defined as a series of highly acidic,relatively high-molecular-weight,and yellow to black colored substances formed during the decay and transformation of plant and microbial remains,ubi...Humic substances(HS),which are defined as a series of highly acidic,relatively high-molecular-weight,and yellow to black colored substances formed during the decay and transformation of plant and microbial remains,ubiquitously occur in nature.Humic substances represent the largest stable organic carbon pool in terrestrial environments and are the central characteristic of the soil.However,the validity of the HS concept and the justification of their extraction procedure have been recently debated.Here,we argue that the traditional humic paradigm is still relevant.Humic substances are distinctive and complex because the extracted HS formed during the humification are chemically distinct from their precursors and are heterogeneous among soils.By reviewing the concept,formation pathways,and stabilization of HS,we propose that the key question facing soil scientists is whether HS are soil microbial residues or unique synthesized compounds.Without revealing the distinctiveness of HS,it is impossible to address this question,as the structure,composition,and reactivity of HS are still poorly known owing to the heterogeneity and geographical variability of HS and the limits of the currently available analytical techniques.In our view,the distinctiveness of HS is fundamental to the soil,and thus further studies should be focused on revealing the distinctiveness of HS and explaining why HS hold this distinctiveness.展开更多
Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholi...Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.展开更多
To address the issues of large volume change and low conductivity of silicon(Si)materials,carbon coatings have been widely employed as surface protection agent and conductive medium to encapsulate the Si materials,whi...To address the issues of large volume change and low conductivity of silicon(Si)materials,carbon coatings have been widely employed as surface protection agent and conductive medium to encapsulate the Si materials,which can improve the electrochemical performance of Si-based electrodes.There has been a strong demand to gain a deeper understanding of the impact of efficient carbon coating over the lithiation and delithiation process of Si materials.Here,we report the first observation of the extended two-phase transformation of carbon-coated Si nanoparticles(Si/C)during electrochemical processes.The Si/C nanoparticles were prepared by sintering Si nanoparticles with polyvinylidene chloride precursor.The Si/C electrode underwent a two-phase transition during the first 20 cycles at 0.2 C,but started to engage in solid solution reaction when the ordered compact carbon coating began to crack.Under higher current density conditions,the electrode was also found to be involved in solid solution reaction,which,however,was due to the overwhelming demand of kinetic property rather than the breaking of the carbon coating.In comparison,the Si/C composites prepared with sucrose possessed more disordered and porous carbon structures,and presented solid solution reaction throughout the entire cycling process.展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modificatio...T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and localization.However,the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished.Here,we report that ubiquitin-specific protease 7(USP7)can stabilize NOTCH1.USP7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of NOTCH1.USP7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this interaction.Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein level.Similarly,pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells.More importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these findings.Overall,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1.Therefore,USP7 may be a promising therapeutic target in the currently incurable T-ALL.展开更多
Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is ef...Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.展开更多
基金supported by the National Natural Science Foundation of China(Nos.41571231 and 41201221)the National Key Research and Development Program of China(No.2016YFD0200304)+3 种基金the Scientific Instrument and Equipment Development Project of Chinese Academy Sciences(CAS)(No.YJKYYQ20170058)the Natural Science Foundation of Jiangsu Province,China(No.BK2012496)the Youth Innovation Promotion Association,CAS(No.2017362)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.19KJB180010)。
文摘Humic substances(HS),which are defined as a series of highly acidic,relatively high-molecular-weight,and yellow to black colored substances formed during the decay and transformation of plant and microbial remains,ubiquitously occur in nature.Humic substances represent the largest stable organic carbon pool in terrestrial environments and are the central characteristic of the soil.However,the validity of the HS concept and the justification of their extraction procedure have been recently debated.Here,we argue that the traditional humic paradigm is still relevant.Humic substances are distinctive and complex because the extracted HS formed during the humification are chemically distinct from their precursors and are heterogeneous among soils.By reviewing the concept,formation pathways,and stabilization of HS,we propose that the key question facing soil scientists is whether HS are soil microbial residues or unique synthesized compounds.Without revealing the distinctiveness of HS,it is impossible to address this question,as the structure,composition,and reactivity of HS are still poorly known owing to the heterogeneity and geographical variability of HS and the limits of the currently available analytical techniques.In our view,the distinctiveness of HS is fundamental to the soil,and thus further studies should be focused on revealing the distinctiveness of HS and explaining why HS hold this distinctiveness.
文摘Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.
基金This study is funded by the Assistant Secretary for Energy Efficiency,Vehicle Technologies Office of the U.S.Department of Energy,under the Si Consortium Program.Electron microscopy experiments are conducted at the National Centre for Electron Microscopy and the Molecular Foundry located at Lawrence Berkeley National Laboratory is supported by the Director,Office of Science,Office of Basic Energy Sciences,the U.S.Department of Energy under Contract No.DE-AC02-05CH11231.
文摘To address the issues of large volume change and low conductivity of silicon(Si)materials,carbon coatings have been widely employed as surface protection agent and conductive medium to encapsulate the Si materials,which can improve the electrochemical performance of Si-based electrodes.There has been a strong demand to gain a deeper understanding of the impact of efficient carbon coating over the lithiation and delithiation process of Si materials.Here,we report the first observation of the extended two-phase transformation of carbon-coated Si nanoparticles(Si/C)during electrochemical processes.The Si/C nanoparticles were prepared by sintering Si nanoparticles with polyvinylidene chloride precursor.The Si/C electrode underwent a two-phase transition during the first 20 cycles at 0.2 C,but started to engage in solid solution reaction when the ordered compact carbon coating began to crack.Under higher current density conditions,the electrode was also found to be involved in solid solution reaction,which,however,was due to the overwhelming demand of kinetic property rather than the breaking of the carbon coating.In comparison,the Si/C composites prepared with sucrose possessed more disordered and porous carbon structures,and presented solid solution reaction throughout the entire cycling process.
基金This work was supported in part by grants from the National Key Research and Development Program of China(no.2017YFA0505200)the National Basic Research Program of China(973 Program)(no.2015CB910403)+3 种基金the National Natural Science Foundation of China(81700475,81670139,81570118,and 81570112)Natural Science Foundation of Shanghai(16ZR1427800)the Science and Technology Committee of Shanghai(15401901800)the Innovation Program of Shanghai Municipal Education Commission(13YZ028).
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling pathway.Recent studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and localization.However,the specific deubiquitinase that affects NOTCH1 protein stability remains unestablished.Here,we report that ubiquitin-specific protease 7(USP7)can stabilize NOTCH1.USP7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of NOTCH1.USP7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this interaction.Depletion of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein level.Similarly,pharmacologic inhibition of USP7 led to apoptosis of T-ALL cells.More importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these findings.Overall,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes NOTCH1.Therefore,USP7 may be a promising therapeutic target in the currently incurable T-ALL.
基金supported by the Natural Science Foundation of Shanghai (21ZR1475600)Science and Technology Commission of Shanghai Municipality (20431900100)+4 种基金Shanghai Science and Technology Committee (19430750100)National Key R&D Program of China (2016YFA0502301 and 2021YFC2301204)Drug development for the newly emerging viral infectious diseases (SIMM010107)Fundamental Research Funds for the Central Universities (2022ZFJH003)Zhejiang Provincial Key Research&Development Program of China (2021C03043 and No.2021C03039).
文摘Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
