Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects agains...Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects against CSG.However,the molecular basis of its therapeutic effect has not been clarified.Herein,we employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q/TOF-MS)based chemical profile identification to determine the chemical components in JHT.Further,we applied network pharmacology to illustrate its molecular mechanisms.A total of 96 chemical constituents were identified in JHT,31 of which were confirmed using reference standards.Based on the bioinformatics analysis using the symptom-guided pharmacological networks of“chi,”“blood,”“pain,”and“inflammation,”and target screening through the interaction probabilities between compounds and targets,matrix metalloproteinase 2(MMP2),dopamine d2 receptor(DRD2),and Aldo-keto reductase family 1 member B1(AKR1B1)were identified as key targets in the therapeutic effect exhibited by JHT against CSG.Moreover,according to the inhibitory activities presented in the literature and binding mode analysis,the structural types of alkaloids,flavonoids,organic acids,including chlorogenic acid(10),caffeic acid(13),(-)-corydalmine(33),(-)-isocorypalmine(36),isochlorogenic acid C(38),isochlorogenic acid A(41),quercetin-3-O-a-L-rhamnoside(42),isochlorogenic acid B(47),quercetin(63),and kaempferol(70)tended to show remarkable activities against CSG.Owing to the above findings,we systematically identified the chemical components of JHT and revealed its molecular mechanisms based on the symptoms associated with CSG.展开更多
Two extended hybrid conjugated systems based on a triphenylamine(TPA) core with two and three peripheral 1,4-dithiafulvenes(DTF) units coded WH-2 and WH-3 as hole-transporting materials(HTMs) applied in perovskite sol...Two extended hybrid conjugated systems based on a triphenylamine(TPA) core with two and three peripheral 1,4-dithiafulvenes(DTF) units coded WH-2 and WH-3 as hole-transporting materials(HTMs) applied in perovskite solar cells(PSCs) are synthesized by facile one-step reaction in good yield over 75%. DTF unit as electron donor can enhance the electron donating ability and the fusion of benzenic ring of TPA with DTF unit may lead to reinforced intermolecular interactions in the solid state. In addition,WH-2 and WH-3 exhibit a pyramid shape containing partial planarity and quasi three-dimensionality features, which is also conducive to enhancing the π-π stacking of molecules in the solid state. The above-mentioned structural characteristics make the two HTMs have good hole mobilities. As a result,WH-2 and WH-3 obtained the high intrinsic hole mobilities of 4.69 × 10^(-4)and 2.18 × 10^(-3)cm^(2)V^(-1)s^(-1)respectively. Finally, the power conversion efficiencies(PCEs) of PSCs with WH-2 and WH-3 as cost-effective dopant-free HTMs are 15.39% and 19.22% respectively and the PCE of PSC with WH-3 is on a par with that of PSC with Li-TFSI/t-BP doped Spiro-OMe TAD(19.67%).展开更多
As one of the five components of Earth's climatic system,the cryosphere has been undergoing rapid shrinking due to global warming.Studies on the formation,evolution,distribution and dynamics of cryospheric compone...As one of the five components of Earth's climatic system,the cryosphere has been undergoing rapid shrinking due to global warming.Studies on the formation,evolution,distribution and dynamics of cryospheric components and their interactions with the human system are of increasing importance to society.In recent decades,the mass loss of glaciers,including the Greenland and Antarctic ice sheets,has accelerated.The extent of sea ice and snow cover has been shrinking,and permafrost has been degrading.The main sustainable development goals in cryospheric regions have been impacted.The shrinking of the cryosphere results in sea-level rise,which is currently affecting,or is soon expected to affect,17 coastal megacities and some small island countries.In East Asia,South Asia and North America,climate anomalies are closely related to the extent of Arctic sea ice and snow cover in the Northern Hemisphere.Increasing freshwater melting from the ice sheets and sea ice may be one reason for the slowdown in Atlantic meridional overturning circulation in the Arctic and Southern Oceans.The foundations of ports and infrastructure in the circum-Arctic permafrost regions suffer from the consequences of permafrost degradation.In high plateaus and mountainous regions,the cryosphere's shrinking has led to fluctuations in river runoff,caused water shortages and increased flooding risks in certain areas.These changes in cryospheric components have shown significant heterogeneity at different temporal and spatial scales.Our results suggest that the quantitative evaluation of future changes in the cryosphere still needs to be improved by enhancing existing observations and model simulations.Theoretical and methodological innovations are required to strengthen social economies'resilience to the impact of cryospheric change.展开更多
Based on Landsat MSS/TM/OLI remote sensing images,glaciers vector data in the Qaidam Basin were extracted for 1977,2002,and 2018,and their spatial-temporal variations were analyzed.Results show that there were 2,050 g...Based on Landsat MSS/TM/OLI remote sensing images,glaciers vector data in the Qaidam Basin were extracted for 1977,2002,and 2018,and their spatial-temporal variations were analyzed.Results show that there were 2,050 glaciers covering an area of 1,693.54±40.96 km2 and having an ice volume of 108.65±2.43 km^3 in the Qaidam Basin in 2018.Glaciers with areas<1.0 km2 accounted for the largest number,while glaciers with areas of 1.0−5.0 km2 accounted for the most glacierized area.In the past 50 years,the number of glaciers decreased by 177,and the glacier area and volume reduced by 338.08 km2(−8.12 km^2/a)and 19.92 km3(−0.48 km^3/a),respectively.Retreat altitudes of glaciers were concentrated at 4,900−5,600 m,4,700−5,200 m,and 5,000−5,600 m and reduced areas accounted for 95.53%,77.80%,and 69.19%in the Kunlun,Qilian,and Altun mountains,respectively.The area of north-oriented glaciers decreased the most(−125.43 km^2),but the west-and east-oriented glaciers retreated at the fastest rate(i.e.,−27.11%and−27.10%).All glaciers showed a decreasing trend in sub-regions of the Qaidam Basin from 1977 to 2018.The decreasing trend was accelerated gradually from northwest to southeast in the northern part of the basin,while glacier change was the smallest in the middle section and gradually accelerated towards both ends of the basin's southern part.The temperature had continued to rise,and the precipitation had increased slowly in the Qaidam Basin during the past 50 years.The continuous rise in air temperature was the main reason for the retreat of glaciers.展开更多
Lithium bis(trifluoromethanesulfonyl)imide(Li-TFSI)/4-tert-butylpyridine(tBP)is a classic doping system for the hole transport material Spiro-OMeTAD in typical n-i-p structure perovskite solar cells(PSCs),but this sys...Lithium bis(trifluoromethanesulfonyl)imide(Li-TFSI)/4-tert-butylpyridine(tBP)is a classic doping system for the hole transport material Spiro-OMeTAD in typical n-i-p structure perovskite solar cells(PSCs),but this system will cause many problems such as high hygroscopicity,Li+migration,pinholes and so on,which hinder PSC from maintaining high efficiency and stability for long-term.In this work,an effective strategy is demonstrated to improve the performance and stability of PSC by replacing t BP with 12-crown-4.The chelation of 12-crown-4 with Li+not only improves the doping effect of Li-TFSI,but also perfectly solves the problems caused by the Li-TFSI/tBP system.The PSC based on this strategy achieved a champion power conversion efficiency(PCE)over 21%,which is significantly better than the pristine device(19.37%).More importantly,the without encapsulated device based on Li-TFSI/12-crown-4 still maintains 87%of the initial PCE even after 60 days exposure in air,while the pristine device only maintains 22%of the initial PCE under the same aging conditions.This strategy paves a novel way for constructing efficient and stable PSCs.展开更多
Food safety is one of the top issues for Chinese consumers. In the summer of 2014,Shanghai-based Husi Food Co Ltd was mired in a food-safety scandal. OSI Group responded to this situation by releasing statements and h...Food safety is one of the top issues for Chinese consumers. In the summer of 2014,Shanghai-based Husi Food Co Ltd was mired in a food-safety scandal. OSI Group responded to this situation by releasing statements and holding China press conference. This study focused on OSI Group's image repair strategies employed in the scandal in Chinese context. A content analysis revealed that OSI Group's image repair relied primarily on six strategies: defeasibility( appalled by the event),bolstering( factory in Henan is state-of-art),minimization( it was an isolated event),corrective action( thorough internal investigation),and mortification( sincerely apologized),and attacking the accuser( launched OSI Food Safety Education Campaign). Basically,OSI Group's mortification without compensation doomed its efforts to failure.Implications for implementing image repair strategies with the combination of crisis types are addressed.展开更多
The pricey prawn scandal of Qingdao in the 2015 National Day Holiday,not only violates the principle of integrity management,but also seriously damages the image of Qingdao—World Famous Tourist City.This study applie...The pricey prawn scandal of Qingdao in the 2015 National Day Holiday,not only violates the principle of integrity management,but also seriously damages the image of Qingdao—World Famous Tourist City.This study applies image repair strategies to Qingdao municipal government departments' attempt to restore its damaged image in crisis communication.Through a discourse analysis,it is found that the government departments mainly adopt the following strategies: denial,evasion of responsibility(defeasibility),reduction of offensiveness(bolstering,compensation),corrective action and mortification.Then we evaluate the effectiveness of this image repair effort.展开更多
Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonat...Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.展开更多
Alternative splicing(AS)is an important approach for pathogens and hosts to remodel transcriptome.However,tuberculosis(TB)-related AS has not been sufficiently explored.Here we presented the first landscape of TB-rela...Alternative splicing(AS)is an important approach for pathogens and hosts to remodel transcriptome.However,tuberculosis(TB)-related AS has not been sufficiently explored.Here we presented the first landscape of TB-related AS by long-read sequencing,and screened four AS events(S100A8-intron1-retention intron,RPS20-exon1-alternaitve promoter,KIF13B-exon4-skipping exon(SE)and UBE2B-exon7-SE)as potential biomarkers in an in-house cohort-1.The validations in an in-house cohort-2(2274 samples)and public datasets(1557 samples)indicated that the latter three AS events are potential promising biomarkers for TB diagnosis,but not for TB progression and prognosis.The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers.Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance.The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression.After heat-killed mycobacterium tuberculosis stimulation,231 ubiquitination proteins in macrophages were differentially expressed,and most of them are apoptosis-related proteins.Taken together,we depicted a global TB-associated splicing profile,developed TB-related AS biomarkers,demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing,offering a novel insight into the pathophysiology of TB.展开更多
The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+C...The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+CLP group was the inverted picture of CLP group in Fig.5G.In Fig.7C,the H&E picture of Clo-Lipo+CLP group was zoom-in picture of L johnsoni+CLP group in Fig.8F.In Fig.SI0B,the H&E picture of ileum in CLP group was zoom-in picture of Anti-IL-10R+CLP group in Fig.S11C.The authors revise the H&E picture of liver in PBS+Lipo+CLP group and the H&E picture of liver in Clo-Lipo+CLP group in Fig.7C.Also,the H&E picture of ileum in CLP group of Fig.S10B have been revised.The correct figures are presented as below.展开更多
Bromodomain PHD-finger transcription factor(BPTF)is the largest subunit of the nucleosome remodeling factor and plays an important role in chromatin remodeling for gene activation through its association with histone ...Bromodomain PHD-finger transcription factor(BPTF)is the largest subunit of the nucleosome remodeling factor and plays an important role in chromatin remodeling for gene activation through its association with histone acetylation or methylation.BPTF is also involved in oncogene transcription in diverse progressions of cancers.Despite clinical trials for inhibitors of bromodomain and extra-terminal family proteins in human cancers,no potent and selective inhibitor targeting the BPTF bromodomain has been discovered.In this study,we identified a potential inhibitor,namely,C620-0696,by computational docking modeling to target bromodomain.Results of biolayer interferometry revealed that compound C620-0696 exhibited high binding affinity to the BPTF bromodomain.Moreover,C620-0696 was cytotoxic in BPTF with a high expression of non-small-cell lung cancer(NSCLC)cells.It suppressed the expression of the BPTF target gene c-MYC,which is known as an oncogenic transcriptional regulator in various cancers.C620-0696 also partially inhibited the migration and colony formation of NSCLC cells owing to apoptosis induction and cell cycle blockage.Thus,our study presents an effective strategy to target a bromodomain factor-mediated tumorigenesis in cancers with small molecules,supporting further exploration of the use of these inhibitors in oncology.展开更多
基金funded by the National Natural Science Foundation of China (Grant Nos.: 81903426 and 81803347)
文摘Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects against CSG.However,the molecular basis of its therapeutic effect has not been clarified.Herein,we employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q/TOF-MS)based chemical profile identification to determine the chemical components in JHT.Further,we applied network pharmacology to illustrate its molecular mechanisms.A total of 96 chemical constituents were identified in JHT,31 of which were confirmed using reference standards.Based on the bioinformatics analysis using the symptom-guided pharmacological networks of“chi,”“blood,”“pain,”and“inflammation,”and target screening through the interaction probabilities between compounds and targets,matrix metalloproteinase 2(MMP2),dopamine d2 receptor(DRD2),and Aldo-keto reductase family 1 member B1(AKR1B1)were identified as key targets in the therapeutic effect exhibited by JHT against CSG.Moreover,according to the inhibitory activities presented in the literature and binding mode analysis,the structural types of alkaloids,flavonoids,organic acids,including chlorogenic acid(10),caffeic acid(13),(-)-corydalmine(33),(-)-isocorypalmine(36),isochlorogenic acid C(38),isochlorogenic acid A(41),quercetin-3-O-a-L-rhamnoside(42),isochlorogenic acid B(47),quercetin(63),and kaempferol(70)tended to show remarkable activities against CSG.Owing to the above findings,we systematically identified the chemical components of JHT and revealed its molecular mechanisms based on the symptoms associated with CSG.
基金the Sichuan Science and Technology Program (2019YJ0162)the National Natural Science Foundation of China (21402023, 51773027)the National Key R@D Program of China (2017YFB0702802) for financial support。
文摘Two extended hybrid conjugated systems based on a triphenylamine(TPA) core with two and three peripheral 1,4-dithiafulvenes(DTF) units coded WH-2 and WH-3 as hole-transporting materials(HTMs) applied in perovskite solar cells(PSCs) are synthesized by facile one-step reaction in good yield over 75%. DTF unit as electron donor can enhance the electron donating ability and the fusion of benzenic ring of TPA with DTF unit may lead to reinforced intermolecular interactions in the solid state. In addition,WH-2 and WH-3 exhibit a pyramid shape containing partial planarity and quasi three-dimensionality features, which is also conducive to enhancing the π-π stacking of molecules in the solid state. The above-mentioned structural characteristics make the two HTMs have good hole mobilities. As a result,WH-2 and WH-3 obtained the high intrinsic hole mobilities of 4.69 × 10^(-4)and 2.18 × 10^(-3)cm^(2)V^(-1)s^(-1)respectively. Finally, the power conversion efficiencies(PCEs) of PSCs with WH-2 and WH-3 as cost-effective dopant-free HTMs are 15.39% and 19.22% respectively and the PCE of PSC with WH-3 is on a par with that of PSC with Li-TFSI/t-BP doped Spiro-OMe TAD(19.67%).
基金This research was supported by Yunnan University(YJRC3201702)the National Natural Science Foundation of China(Grant Nos.41761144075,41690142,41941015,41771075,41871096,41671057,41801052,41561016,41701061,41861013)the Ministry of Science and Technology(2013FY111400).
文摘As one of the five components of Earth's climatic system,the cryosphere has been undergoing rapid shrinking due to global warming.Studies on the formation,evolution,distribution and dynamics of cryospheric components and their interactions with the human system are of increasing importance to society.In recent decades,the mass loss of glaciers,including the Greenland and Antarctic ice sheets,has accelerated.The extent of sea ice and snow cover has been shrinking,and permafrost has been degrading.The main sustainable development goals in cryospheric regions have been impacted.The shrinking of the cryosphere results in sea-level rise,which is currently affecting,or is soon expected to affect,17 coastal megacities and some small island countries.In East Asia,South Asia and North America,climate anomalies are closely related to the extent of Arctic sea ice and snow cover in the Northern Hemisphere.Increasing freshwater melting from the ice sheets and sea ice may be one reason for the slowdown in Atlantic meridional overturning circulation in the Arctic and Southern Oceans.The foundations of ports and infrastructure in the circum-Arctic permafrost regions suffer from the consequences of permafrost degradation.In high plateaus and mountainous regions,the cryosphere's shrinking has led to fluctuations in river runoff,caused water shortages and increased flooding risks in certain areas.These changes in cryospheric components have shown significant heterogeneity at different temporal and spatial scales.Our results suggest that the quantitative evaluation of future changes in the cryosphere still needs to be improved by enhancing existing observations and model simulations.Theoretical and methodological innovations are required to strengthen social economies'resilience to the impact of cryospheric change.
文摘Based on Landsat MSS/TM/OLI remote sensing images,glaciers vector data in the Qaidam Basin were extracted for 1977,2002,and 2018,and their spatial-temporal variations were analyzed.Results show that there were 2,050 glaciers covering an area of 1,693.54±40.96 km2 and having an ice volume of 108.65±2.43 km^3 in the Qaidam Basin in 2018.Glaciers with areas<1.0 km2 accounted for the largest number,while glaciers with areas of 1.0−5.0 km2 accounted for the most glacierized area.In the past 50 years,the number of glaciers decreased by 177,and the glacier area and volume reduced by 338.08 km2(−8.12 km^2/a)and 19.92 km3(−0.48 km^3/a),respectively.Retreat altitudes of glaciers were concentrated at 4,900−5,600 m,4,700−5,200 m,and 5,000−5,600 m and reduced areas accounted for 95.53%,77.80%,and 69.19%in the Kunlun,Qilian,and Altun mountains,respectively.The area of north-oriented glaciers decreased the most(−125.43 km^2),but the west-and east-oriented glaciers retreated at the fastest rate(i.e.,−27.11%and−27.10%).All glaciers showed a decreasing trend in sub-regions of the Qaidam Basin from 1977 to 2018.The decreasing trend was accelerated gradually from northwest to southeast in the northern part of the basin,while glacier change was the smallest in the middle section and gradually accelerated towards both ends of the basin's southern part.The temperature had continued to rise,and the precipitation had increased slowly in the Qaidam Basin during the past 50 years.The continuous rise in air temperature was the main reason for the retreat of glaciers.
基金the National Natural Science Foundation of China(22175029 and 62104031)the Sichuan Science and Technology Program(2019YJ0162)+3 种基金the Open Foundation of State Key Laboratory of Electronic Thin Films and Integrated Devices(KFJJ202109)the Natural Science Foundation of Shenzhen Innovation Committee(JCYJ20210324135614040)the Technical Field Funds of 173 Project(2021-JCJQ-JJ-0663)the Fundamental Research Funds for the Central Universities of China(ZYGX2021J010 and Y030202059018023)for financial support。
文摘Lithium bis(trifluoromethanesulfonyl)imide(Li-TFSI)/4-tert-butylpyridine(tBP)is a classic doping system for the hole transport material Spiro-OMeTAD in typical n-i-p structure perovskite solar cells(PSCs),but this system will cause many problems such as high hygroscopicity,Li+migration,pinholes and so on,which hinder PSC from maintaining high efficiency and stability for long-term.In this work,an effective strategy is demonstrated to improve the performance and stability of PSC by replacing t BP with 12-crown-4.The chelation of 12-crown-4 with Li+not only improves the doping effect of Li-TFSI,but also perfectly solves the problems caused by the Li-TFSI/tBP system.The PSC based on this strategy achieved a champion power conversion efficiency(PCE)over 21%,which is significantly better than the pristine device(19.37%).More importantly,the without encapsulated device based on Li-TFSI/12-crown-4 still maintains 87%of the initial PCE even after 60 days exposure in air,while the pristine device only maintains 22%of the initial PCE under the same aging conditions.This strategy paves a novel way for constructing efficient and stable PSCs.
文摘Food safety is one of the top issues for Chinese consumers. In the summer of 2014,Shanghai-based Husi Food Co Ltd was mired in a food-safety scandal. OSI Group responded to this situation by releasing statements and holding China press conference. This study focused on OSI Group's image repair strategies employed in the scandal in Chinese context. A content analysis revealed that OSI Group's image repair relied primarily on six strategies: defeasibility( appalled by the event),bolstering( factory in Henan is state-of-art),minimization( it was an isolated event),corrective action( thorough internal investigation),and mortification( sincerely apologized),and attacking the accuser( launched OSI Food Safety Education Campaign). Basically,OSI Group's mortification without compensation doomed its efforts to failure.Implications for implementing image repair strategies with the combination of crisis types are addressed.
文摘The pricey prawn scandal of Qingdao in the 2015 National Day Holiday,not only violates the principle of integrity management,but also seriously damages the image of Qingdao—World Famous Tourist City.This study applies image repair strategies to Qingdao municipal government departments' attempt to restore its damaged image in crisis communication.Through a discourse analysis,it is found that the government departments mainly adopt the following strategies: denial,evasion of responsibility(defeasibility),reduction of offensiveness(bolstering,compensation),corrective action and mortification.Then we evaluate the effectiveness of this image repair effort.
基金funded by regular grants and joint grant(File No.0096/2018/A3,0111/2020/A3 and 0056/2020/AMJ)Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(File No.001/2020/ALC)+4 种基金supported by the Macao Science and Technology Development Fundsupported by 2020 Young Qihuang Scholar funded by the National Administration of Traditional Chinese Medicinesupported by National Natural Science Foundation of China(82025036)supported by the Start-up Research Grant of University of Macao(SRG2022-00020-FHS,China)the Faculty of Health Science,University of Macao(Macao,China).
文摘Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.
基金Thanks to Xuan Chen at West China Hospital of Stomatology,Sichuan University for providing THP-1 cell line.Thanks to Xiaohuan Su at Core Facilities of West China Hospital for cell line identification.Thanks to Sisi Wu,Jinkui Pi,and Yufei Cheng at Core Facilities of West China Hospital for their help on capturing fluorescence signal by using confocal laser scanning microscope(Leica).Thanks to Dr.Li Yu at Tsinghua University,and Chengqi Yi at Peking University for their advices on writing.This work was funded by the National Science&Technology Pillar Program during the 13th Five-year Plan Period[Grant number:2018ZX10715003]National Natural Science Foundation of China[Grant number:82272416,Grant number:U20A20394].
文摘Alternative splicing(AS)is an important approach for pathogens and hosts to remodel transcriptome.However,tuberculosis(TB)-related AS has not been sufficiently explored.Here we presented the first landscape of TB-related AS by long-read sequencing,and screened four AS events(S100A8-intron1-retention intron,RPS20-exon1-alternaitve promoter,KIF13B-exon4-skipping exon(SE)and UBE2B-exon7-SE)as potential biomarkers in an in-house cohort-1.The validations in an in-house cohort-2(2274 samples)and public datasets(1557 samples)indicated that the latter three AS events are potential promising biomarkers for TB diagnosis,but not for TB progression and prognosis.The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers.Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance.The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression.After heat-killed mycobacterium tuberculosis stimulation,231 ubiquitination proteins in macrophages were differentially expressed,and most of them are apoptosis-related proteins.Taken together,we depicted a global TB-associated splicing profile,developed TB-related AS biomarkers,demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing,offering a novel insight into the pathophysiology of TB.
文摘The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+CLP group was the inverted picture of CLP group in Fig.5G.In Fig.7C,the H&E picture of Clo-Lipo+CLP group was zoom-in picture of L johnsoni+CLP group in Fig.8F.In Fig.SI0B,the H&E picture of ileum in CLP group was zoom-in picture of Anti-IL-10R+CLP group in Fig.S11C.The authors revise the H&E picture of liver in PBS+Lipo+CLP group and the H&E picture of liver in Clo-Lipo+CLP group in Fig.7C.Also,the H&E picture of ileum in CLP group of Fig.S10B have been revised.The correct figures are presented as below.
基金supported by Macao Science and Technology Development Fund(Nos.102/2016/A3,130/2017/A3,0003/2018/A1,and 046/2016/A2).
文摘Bromodomain PHD-finger transcription factor(BPTF)is the largest subunit of the nucleosome remodeling factor and plays an important role in chromatin remodeling for gene activation through its association with histone acetylation or methylation.BPTF is also involved in oncogene transcription in diverse progressions of cancers.Despite clinical trials for inhibitors of bromodomain and extra-terminal family proteins in human cancers,no potent and selective inhibitor targeting the BPTF bromodomain has been discovered.In this study,we identified a potential inhibitor,namely,C620-0696,by computational docking modeling to target bromodomain.Results of biolayer interferometry revealed that compound C620-0696 exhibited high binding affinity to the BPTF bromodomain.Moreover,C620-0696 was cytotoxic in BPTF with a high expression of non-small-cell lung cancer(NSCLC)cells.It suppressed the expression of the BPTF target gene c-MYC,which is known as an oncogenic transcriptional regulator in various cancers.C620-0696 also partially inhibited the migration and colony formation of NSCLC cells owing to apoptosis induction and cell cycle blockage.Thus,our study presents an effective strategy to target a bromodomain factor-mediated tumorigenesis in cancers with small molecules,supporting further exploration of the use of these inhibitors in oncology.
基金The authors are grateful to the National Natural Science Foundation of China,the Excellent Young Teachers Program of Lanzhou University of Technology,Zhejiang Provincial Natural Science Foundation of China,the open fund of the Key Laboratory of the New Animal Drug Project of Gansu Province and the Key Laboratory of Veterinary Pharmaceutical Development of the Ministry of Agriculture