AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice we...AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.展开更多
Background Mycoplasma pneumonia （M.pneumoniae） is one of the key pathogens of community-acquired pneumonia.A global pandemic of M.pneumoniae has occurred since 2010.The aim of this study was to survey the prevalence...Background Mycoplasma pneumonia （M.pneumoniae） is one of the key pathogens of community-acquired pneumonia.A global pandemic of M.pneumoniae has occurred since 2010.The aim of this study was to survey the prevalence of M.pneumoniae in children in Beijing from 2007-2012.Methods A total of 3 073 clinical specimens were obtained from pediatric patients with respiratory tract infections from January 2007 to December 2012,and examined by nested polymerase chain reaction.PCR products were visualized by 2％ agarose gel electrophoresis,positive products sequenced,and compared with reference sequences in GenBank.Macrolide resistance-associated mutations were also detected for some positive samples.Results Of the 3 073 specimens,588 （19.13％） were positive for M.pneumoniae,12.4％ of which were accompanied by viral infections.Positive rates for M.pneumoniae were highest in 2007 and 2012,showing a significant difference when compared with other years.Infections tended to occur in autumn and winter and positive rates were significantly higher for children aged 3-16.The rate of macrolide resistance-associated mutations was 90.7％,and the predominant mutation was an A→G transition （89.92％） at position 2063 in domain V of the 23S rRNA gene.Conclusions M.pneumoniae outbreaks occurred in 2007 and 2012 in pediatric patients in Beijing,which is consistent with the global prevalence of M.pneumoniae.M.pneumoniae can cause multi-system infections in children,and may be accompanied with viral infections.We determined that school-age children are more susceptible to this disease,particularly in autumn and winter.Gene mutations associated with macrolide resistance were very common in M.pneumoniae-positive specimens during this period in Beijing.展开更多
It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription fa...It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all ana-lyzed WRKY proteins recognize the TrGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcrip-tion factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biologi- cal processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.展开更多
Sawuer region is located in west Junggar, Jimunai County of Altay district and Hefeng County of Tacheng district, Xinjiang. The region is along the north margin of Kazakstan-Junggar plate. The intrusions (mainly acid)...Sawuer region is located in west Junggar, Jimunai County of Altay district and Hefeng County of Tacheng district, Xinjiang. The region is along the north margin of Kazakstan-Junggar plate. The intrusions (mainly acid) are widespread. Qiaqihai and Kuoyitasi intrusions are important in the region, with the characteristics of A-type granite. Further investigations indicate that they belong to A2-type granite that formed in extension tectonic setting of post collision. The REE chon-drite-normalized patterns of the intrusions show LREE enrichment and the δ Eu values are lower. The Nd, Sr, Pb isotope compositions of the intrusions indicate a mantle source, while the low δ 18O values resulted from the isotope exchange between intrusion and meteoric water. According to SHRIMP U-Pb age analysis results, the crystallization age of Qiaqihai intrusion is 290.7 ± 9.3 Ma (1σ ), and that of Kuoyitasi intrusion is 297.9 ± 4.6 Ma (1σ ), corresponding to the beginning of early Permian. The A2-type granites indicate that the region was in the extension period of the post-collisional stage at the beginning of early Permian in the Sawuer region. The A-type granites in the Sawuer region in west Junggar discovered from this work is analogous to the A-type granites found in east Junggar of the Ulungur alkali granites belt. The confirmation of post-collisional A-type granites of early Permian in the Sawuer region provides new evidence for the regional vertical continental crust growth in early Per-mian. The former proposed Ulungur alkali granites belt can extend from east Ulungur through west Ulungur and to Zhaisang in Kazakstan westwards.展开更多
Background:The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan,Hubei Province of China since December 2019.This study was performed to analyze the clinical characteristics of p...Background:The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan,Hubei Province of China since December 2019.This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease(COVID-19).Methods:Clinical data were collected from two tertiary hospitals in Wuhan.A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19(death group)and we compare them with recovered patients(recovered group).Continuous variables were analyzed using the Mann-WhitneyU test.Categorical variables were analyzed byχ2 test or Fisher exact test as appropriate.Results:Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients.The median age of the death group was older than the recovered group(69[62,74]vs.40[33,57]years,Z=9.738,P<0.001).More patients in the death group had underlying diseases(72.5%vs.41.4%,χ2=22.105,P<0.001).Patients in the death group had a significantly longer time of illness onset to hospitalization(10.0[6.5,12.0]vs.7.0[5.0,10.0]days,Z=3.216,P=0.001).On admission,the proportions of patients with symptoms of dyspnea(70.6%vs.19.0%,χ2=60.905,P<0.001)and expectoration(32.1%vs.12.1%,χ2=13.250,P<0.001)were significantly higher in the death group.The blood oxygen saturation was significantly lower in the death group(85[77,91]%vs.97[95,98]%,Z=10.625,P<0.001).The white blood cell(WBC)in death group was significantly higher on admission(7.23[4.87,11.17]vs.4.52[3.62,5.88]×109/L,Z=7.618,P<0.001).Patients in the death group exhibited significantly lower lymphocyte count(0.63[0.40,0.79]vs.1.00[0.72,1.27]×109/L,Z=8.037,P<0.001)and lymphocyte percentage(7.10[4.45,12.73]%vs.23.50[15.27,31.25]%,Z=10.315,P<0.001)on admission,and the lymphocyte percentage continued to decrease during hospitalization(7.10[4.45,12.73]%vs.2.91[1.79,6.13]%,Z=5.242,P<0.001).Alanine transaminase(22.00[15.00,34.00]vs.18.70[13.00,30.38]U/L,Z=2.592,P=0展开更多
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the ...Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.展开更多
The Large sky Area Multi-Object Fiber Spectroscopic Telescope（LAMOST） general survey is a spectroscopic survey that will eventually cover approximately half of the celestial sphere and collect 10 million spectra of ...The Large sky Area Multi-Object Fiber Spectroscopic Telescope（LAMOST） general survey is a spectroscopic survey that will eventually cover approximately half of the celestial sphere and collect 10 million spectra of stars, galaxies and QSOs. Objects in both the pilot survey and the first year regular survey are included in the LAMOST DR1. The pilot survey started in October 2011 and ended in June 2012, and the data have been released to the public as the LAMOST Pilot Data Release in August 2012. The regular survey started in September 2012, and completed its first year of operation in June 2013. The LAMOST DR1 includes a total of 1202 plates containing 2 955 336 spectra, of which 1 790 879 spectra have observed signalto-noise ratio（SNR） ≥ 10. All data with SNR ≥ 2 are formally released as LAMOST DR1 under the LAMOST data policy. This data release contains a total of 2 204 696 spectra, of which 1 944 329 are stellar spectra, 12 082 are galaxy spectra and 5017 are quasars. The DR1 not only includes spectra, but also three stellar catalogs with measured parameters： late A,FGK-type stars with high quality spectra（1 061 918 entries）, A-type stars（100 073 entries）, and M-type stars（121 522 entries）. This paper introduces the survey design, the observational and instrumental limitations, data reduction and analysis, and some caveats. A description of the FITS structure of spectral files and parameter catalogs is also provided.展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
Soil aggregate stability,an important index of the physical characteristics of a soil,can provide a good indication of a soil’s erodibility,and deserves special consideration in regions with cold climate.The objectiv...Soil aggregate stability,an important index of the physical characteristics of a soil,can provide a good indication of a soil’s erodibility,and deserves special consideration in regions with cold climate.The objective of this study was to study the effect of freeze-thaw on soil water-stable aggregates in the black soil region of Northeast China.Samples of a typical black soil in the region were collected to measure water-stable aggregates after freeze-thaw under different conditions(i.e.,initial moisture contents,freezethaw cycles and freezing temperatures)by wet-sieving into eight particle size groups(>10,10–6,6–5,5–3,3–2,2–1,1–0.5,and0.5–0.25 mm).Freeze-thaw had the most effect on aggregate stability when the samples had an initial moisture content of 400 g kg-1.The water-stable aggregates of the four larger particle size groups(>5,5–3,3–2,and 2–1 mm)reached a peak stability value,but those of the two smaller particle size groups(1–0.5 and 0.5–0.25 mm)reached a minimum value when the soil moisture content was 400 g kg-1.Water-stable aggregates of the four larger particle size groups decreased while those of the two smaller particle size groups increased with the increase of freeze-thaw cycles.As temperatures fell,the water-stable aggregates of the four larger particle size groups decreased while those of the two smaller particle size groups increased.展开更多
基金the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491,No.81470840 and No.31400001100 Talents Program,No.XBR2011007h
文摘AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
基金This work was supported by the grants from the Beijing Natural Science Foundation （No.7112019） and the Beijing City Talent Training Project Fund （No.20071A0303200118）.
文摘Background Mycoplasma pneumonia （M.pneumoniae） is one of the key pathogens of community-acquired pneumonia.A global pandemic of M.pneumoniae has occurred since 2010.The aim of this study was to survey the prevalence of M.pneumoniae in children in Beijing from 2007-2012.Methods A total of 3 073 clinical specimens were obtained from pediatric patients with respiratory tract infections from January 2007 to December 2012,and examined by nested polymerase chain reaction.PCR products were visualized by 2％ agarose gel electrophoresis,positive products sequenced,and compared with reference sequences in GenBank.Macrolide resistance-associated mutations were also detected for some positive samples.Results Of the 3 073 specimens,588 （19.13％） were positive for M.pneumoniae,12.4％ of which were accompanied by viral infections.Positive rates for M.pneumoniae were highest in 2007 and 2012,showing a significant difference when compared with other years.Infections tended to occur in autumn and winter and positive rates were significantly higher for children aged 3-16.The rate of macrolide resistance-associated mutations was 90.7％,and the predominant mutation was an A→G transition （89.92％） at position 2063 in domain V of the 23S rRNA gene.Conclusions M.pneumoniae outbreaks occurred in 2007 and 2012 in pediatric patients in Beijing,which is consistent with the global prevalence of M.pneumoniae.M.pneumoniae can cause multi-system infections in children,and may be accompanied with viral infections.We determined that school-age children are more susceptible to this disease,particularly in autumn and winter.Gene mutations associated with macrolide resistance were very common in M.pneumoniae-positive specimens during this period in Beijing.
文摘It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all ana-lyzed WRKY proteins recognize the TrGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcrip-tion factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biologi- cal processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.
文摘Sawuer region is located in west Junggar, Jimunai County of Altay district and Hefeng County of Tacheng district, Xinjiang. The region is along the north margin of Kazakstan-Junggar plate. The intrusions (mainly acid) are widespread. Qiaqihai and Kuoyitasi intrusions are important in the region, with the characteristics of A-type granite. Further investigations indicate that they belong to A2-type granite that formed in extension tectonic setting of post collision. The REE chon-drite-normalized patterns of the intrusions show LREE enrichment and the δ Eu values are lower. The Nd, Sr, Pb isotope compositions of the intrusions indicate a mantle source, while the low δ 18O values resulted from the isotope exchange between intrusion and meteoric water. According to SHRIMP U-Pb age analysis results, the crystallization age of Qiaqihai intrusion is 290.7 ± 9.3 Ma (1σ ), and that of Kuoyitasi intrusion is 297.9 ± 4.6 Ma (1σ ), corresponding to the beginning of early Permian. The A2-type granites indicate that the region was in the extension period of the post-collisional stage at the beginning of early Permian in the Sawuer region. The A-type granites in the Sawuer region in west Junggar discovered from this work is analogous to the A-type granites found in east Junggar of the Ulungur alkali granites belt. The confirmation of post-collisional A-type granites of early Permian in the Sawuer region provides new evidence for the regional vertical continental crust growth in early Per-mian. The former proposed Ulungur alkali granites belt can extend from east Ulungur through west Ulungur and to Zhaisang in Kazakstan westwards.
文摘Background:The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan,Hubei Province of China since December 2019.This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease(COVID-19).Methods:Clinical data were collected from two tertiary hospitals in Wuhan.A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19(death group)and we compare them with recovered patients(recovered group).Continuous variables were analyzed using the Mann-WhitneyU test.Categorical variables were analyzed byχ2 test or Fisher exact test as appropriate.Results:Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients.The median age of the death group was older than the recovered group(69[62,74]vs.40[33,57]years,Z=9.738,P<0.001).More patients in the death group had underlying diseases(72.5%vs.41.4%,χ2=22.105,P<0.001).Patients in the death group had a significantly longer time of illness onset to hospitalization(10.0[6.5,12.0]vs.7.0[5.0,10.0]days,Z=3.216,P=0.001).On admission,the proportions of patients with symptoms of dyspnea(70.6%vs.19.0%,χ2=60.905,P<0.001)and expectoration(32.1%vs.12.1%,χ2=13.250,P<0.001)were significantly higher in the death group.The blood oxygen saturation was significantly lower in the death group(85[77,91]%vs.97[95,98]%,Z=10.625,P<0.001).The white blood cell(WBC)in death group was significantly higher on admission(7.23[4.87,11.17]vs.4.52[3.62,5.88]×109/L,Z=7.618,P<0.001).Patients in the death group exhibited significantly lower lymphocyte count(0.63[0.40,0.79]vs.1.00[0.72,1.27]×109/L,Z=8.037,P<0.001)and lymphocyte percentage(7.10[4.45,12.73]%vs.23.50[15.27,31.25]%,Z=10.315,P<0.001)on admission,and the lymphocyte percentage continued to decrease during hospitalization(7.10[4.45,12.73]%vs.2.91[1.79,6.13]%,Z=5.242,P<0.001).Alanine transaminase(22.00[15.00,34.00]vs.18.70[13.00,30.38]U/L,Z=2.592,P=0
基金Project supported by the National Basic Research Program(973)of China(No.2012CB518900)the National Natural Science Foundation of China(Nos.31160240 and 31260621)+2 种基金the National Major Scientific and Technological Special Project during the Twelfth Five-year Plan Period of China(No.2012ZX10002006)the Hangzhou Normal University Supporting Project(No.PE13002004042)the Natural Science Foundation of Jiangxi Province(No.20114BAB204016),China
文摘Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.
基金funded by the National Basic Research Program of China (973 Program, 2014CB845700)the National Natural Science Foundation of China (Grant Nos. 11390371)Funding for the project has been provided by the National Development and Reform Commission
文摘The Large sky Area Multi-Object Fiber Spectroscopic Telescope（LAMOST） general survey is a spectroscopic survey that will eventually cover approximately half of the celestial sphere and collect 10 million spectra of stars, galaxies and QSOs. Objects in both the pilot survey and the first year regular survey are included in the LAMOST DR1. The pilot survey started in October 2011 and ended in June 2012, and the data have been released to the public as the LAMOST Pilot Data Release in August 2012. The regular survey started in September 2012, and completed its first year of operation in June 2013. The LAMOST DR1 includes a total of 1202 plates containing 2 955 336 spectra, of which 1 790 879 spectra have observed signalto-noise ratio（SNR） ≥ 10. All data with SNR ≥ 2 are formally released as LAMOST DR1 under the LAMOST data policy. This data release contains a total of 2 204 696 spectra, of which 1 944 329 are stellar spectra, 12 082 are galaxy spectra and 5017 are quasars. The DR1 not only includes spectra, but also three stellar catalogs with measured parameters： late A,FGK-type stars with high quality spectra（1 061 918 entries）, A-type stars（100 073 entries）, and M-type stars（121 522 entries）. This paper introduces the survey design, the observational and instrumental limitations, data reduction and analysis, and some caveats. A description of the FITS structure of spectral files and parameter catalogs is also provided.
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
基金Supported by the National Natural Science Foundation of China(Nos.41071183 and 40601054)
文摘Soil aggregate stability,an important index of the physical characteristics of a soil,can provide a good indication of a soil’s erodibility,and deserves special consideration in regions with cold climate.The objective of this study was to study the effect of freeze-thaw on soil water-stable aggregates in the black soil region of Northeast China.Samples of a typical black soil in the region were collected to measure water-stable aggregates after freeze-thaw under different conditions(i.e.,initial moisture contents,freezethaw cycles and freezing temperatures)by wet-sieving into eight particle size groups(>10,10–6,6–5,5–3,3–2,2–1,1–0.5,and0.5–0.25 mm).Freeze-thaw had the most effect on aggregate stability when the samples had an initial moisture content of 400 g kg-1.The water-stable aggregates of the four larger particle size groups(>5,5–3,3–2,and 2–1 mm)reached a peak stability value,but those of the two smaller particle size groups(1–0.5 and 0.5–0.25 mm)reached a minimum value when the soil moisture content was 400 g kg-1.Water-stable aggregates of the four larger particle size groups decreased while those of the two smaller particle size groups increased with the increase of freeze-thaw cycles.As temperatures fell,the water-stable aggregates of the four larger particle size groups decreased while those of the two smaller particle size groups increased.
