Flower development is one of the most vital pathways in plant development, during which the epigenetic regulation of gene expression is essential. DNA methylation, the most conserved epigenetic modification, participa...Flower development is one of the most vital pathways in plant development, during which the epigenetic regulation of gene expression is essential. DNA methylation, the most conserved epigenetic modification, participates in gene expression regulation and transposable element silencing. Honeysuckle(Lonicera japonica) is an important medicinal plant renowned for its colorful and fragrant flowers. Honeysuckle flowers change color from white to gold as a result of carotenoid accumulation during development. However, the role of DNA methylation in flower color changes is not well understood in L. japonica. Here, we performed whole-genome bisulfite sequencing and transcriptome sequencing during flowering development in honeysuckle. The results showed that a decrease in the levels of genome-wide average DNA methylation during flower development and changes in DNA methylation were associated with the expression of demethylase genes. Moreover, many genes involved in carotenoid biosynthesis and degradation, such as Lj PSY1, LjPDS1, LjLCYE, and LjCCD4, have altered expression levels because of hypomethylation, indicating that DNA methylation plays an important role in flower color changes in honeysuckle. Taken together, our data provide epigenetic insights into flower development and color change in honeysuckles.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 centuries.However,the current practice of obtaining it through bear farming is under scrutiny for its adve...Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 centuries.However,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare.Here,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear bile.This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic constituents.Through the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB formulations.The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materials,and independence from threatened or wild resources.Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile(DBB).Furthermore,preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB.This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.展开更多
Panicle architecture is an agronomic determinant of crop yield and a target for cereal crop improvement.To investigate its molecular mechanisms in rice,we performed map-based cloning and characterization of OPEN PANIC...Panicle architecture is an agronomic determinant of crop yield and a target for cereal crop improvement.To investigate its molecular mechanisms in rice,we performed map-based cloning and characterization of OPEN PANICLE 1(OP1),a gain-of-function allele of LIGULELESS 1(LG1),controlling the spread-panicle phenotype.This allele results from a 48-bp deletion in the LG1 upstream region and promotes pulvinus development at the base of the primary branch.Increased OP1 expression and altered panicle phenotype in chimeric transgenic plants and upstream-region knockout mutants indicated that the deletion regulates spread-panicle architecture in the mutant spread panicle 1(sp1).Knocking out BRASSINOSTEROID UPREGULATED1(BU1)gene in the background of OP1 complementary plants resulted in compact panicles,suggesting OP1 may regulate inflorescence architecture via the brassinosteroid signaling pathway.We regard that manipulating the upstream regulatory region of OP1 or genes involved in BR signal pathway could be an efficient way to improve rice inflorescence architecture.展开更多
In a genome-wide association study,we identified a rice UDP-glycosyltransferase gene,OsUGT706D2,whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid(ABA).OsUGT706...In a genome-wide association study,we identified a rice UDP-glycosyltransferase gene,OsUGT706D2,whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid(ABA).OsUGT706D2 positively regulated the biosynthesis of tricin-4’-O-(syringyl alcohol)ether-7-O-glucoside at both the transcriptional and metabolic levels.OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid(ABA)signaling pathway.Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance.ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance.These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.展开更多
LZ91 Mg-Li alloy plates with three types of initial texture were rolled by 70%reduction at both room temperature and 200℃to explore the rolling texture formation ofα-Mg phase.The results showed that the rolling text...LZ91 Mg-Li alloy plates with three types of initial texture were rolled by 70%reduction at both room temperature and 200℃to explore the rolling texture formation ofα-Mg phase.The results showed that the rolling texture is largely affected by the initial texture.All the samples exhibited two main texture components as RD-split double peaks texture and TD-split double peaks texture after large strain rolling.The intensity of the two texture components was strongly influenced by the initial orientation and rolling temperature.Extension twinning altered the large-split non-basal orientation to a near basal one at low rolling strain.The basal orientation induced by twinning is unstable,which finally transmitted to the RD-split texture.The strong TD-split texture formed due to slip-induced orientation transition from its initial orientation.The competition between prismatic and basal slip determined the intensity and tilt angle of the TD-split texture.By increasing the rolling temperature,the TD-split texture component was enhanced in all three samples.Limitation of extension twinning behavior and the promotion of prismatic slip at elevated temperature are the main reasons for the difference in hot and cold rolling texture.展开更多
BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification ...BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.展开更多
Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmac...Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.展开更多
Viscous behavior is important for the process design, especially for the non-Newtonian fluid. In this study, the viscous behaviors of slurry, i.e., 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)im ide([Hmim]...Viscous behavior is important for the process design, especially for the non-Newtonian fluid. In this study, the viscous behaviors of slurry, i.e., 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)im ide([Hmim][NTf_(2)])/titanium dioxide(TiO_(2))-polyethylene glycol(PEG200), were determined experimentally and systematically. The pressure drop was estimated when [Hmim][NTf_(2)]/TiO_(2)-PEG200 was used as the solvent in the absorption/desorption towers. The results show that the slurry belongs to the non-Newtonian fluid with shear-thinning behavior. High temperature and low solid content are beneficial to reduce the viscosity of [Hmim][NTf_(2)]/TiO_(2)-PEG200, and the presence of [Hmim][NTf_(2)] can effectively reduce the viscosity of the slurry. In addition, high temperature is preferable for reducing the pressure drop, and the pressure drop of slurry with the solid content value of 8.0%(mass) can reduce by 28.0%when the temperature increases from 313 to 333 K.展开更多
Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lnc...Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.展开更多
为研究串联发射的弹丸在不同起始速度下动态挤进膛线的力学机理与运动特点,以30 mm火炮为对象分析了串联发射方式的内弹道物理过程,建立了弹丸与坡膛的有限元模型,采用LS-DYNA软件进行了挤进过程的有限元仿真。研究结果表明:挤进过程中...为研究串联发射的弹丸在不同起始速度下动态挤进膛线的力学机理与运动特点,以30 mm火炮为对象分析了串联发射方式的内弹道物理过程,建立了弹丸与坡膛的有限元模型,采用LS-DYNA软件进行了挤进过程的有限元仿真。研究结果表明:挤进过程中,弹带变形规律不受挤进起始速度的影响,均是逐步被膛线刻槽并发生塑性变形;起始速度由5 m·s^(-1)增加至400 m·s^(-1),弹带等效应力峰值从611.8 MPa升高至717.5 MPa,弹带塑性应变最大值从0.89降低至0.75,挤进阻力峰值从为20.3 k N提高至22.9 k N,挤进完成后的摩擦阻力从0提高至3.5 k N,挤进起始速度增加导致了弹带材料应变率、塑性流动应力与挤进阻力的改变,影响弹丸挤进后的内弹道过程;3发弹串联发射时,首发弹20个节点轴向速度的标准差为8.3 m·s^(-1),后续弹分别为18.2,26.7 m·s^(-1),后续弹挤进时的振动冲击效应较首发弹显著。展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 32160142, 81873095)。
文摘Flower development is one of the most vital pathways in plant development, during which the epigenetic regulation of gene expression is essential. DNA methylation, the most conserved epigenetic modification, participates in gene expression regulation and transposable element silencing. Honeysuckle(Lonicera japonica) is an important medicinal plant renowned for its colorful and fragrant flowers. Honeysuckle flowers change color from white to gold as a result of carotenoid accumulation during development. However, the role of DNA methylation in flower color changes is not well understood in L. japonica. Here, we performed whole-genome bisulfite sequencing and transcriptome sequencing during flowering development in honeysuckle. The results showed that a decrease in the levels of genome-wide average DNA methylation during flower development and changes in DNA methylation were associated with the expression of demethylase genes. Moreover, many genes involved in carotenoid biosynthesis and degradation, such as Lj PSY1, LjPDS1, LjLCYE, and LjCCD4, have altered expression levels because of hypomethylation, indicating that DNA methylation plays an important role in flower color changes in honeysuckle. Taken together, our data provide epigenetic insights into flower development and color change in honeysuckles.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
基金supported by the Major Program of National Natural Science Foundation of China(T2192970-T2192974)the CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-027).
文摘Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 centuries.However,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare.Here,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear bile.This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic constituents.Through the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB formulations.The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materials,and independence from threatened or wild resources.Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile(DBB).Furthermore,preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB.This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.
基金supported by the National Natural Science Foundation of China(31925029,31471457)the National Key Research and Development Project of China(2021YFD120010105)Guangdong Key Laboratory of New Technology in Rice Breeding(2020B1212060047)。
文摘Panicle architecture is an agronomic determinant of crop yield and a target for cereal crop improvement.To investigate its molecular mechanisms in rice,we performed map-based cloning and characterization of OPEN PANICLE 1(OP1),a gain-of-function allele of LIGULELESS 1(LG1),controlling the spread-panicle phenotype.This allele results from a 48-bp deletion in the LG1 upstream region and promotes pulvinus development at the base of the primary branch.Increased OP1 expression and altered panicle phenotype in chimeric transgenic plants and upstream-region knockout mutants indicated that the deletion regulates spread-panicle architecture in the mutant spread panicle 1(sp1).Knocking out BRASSINOSTEROID UPREGULATED1(BU1)gene in the background of OP1 complementary plants resulted in compact panicles,suggesting OP1 may regulate inflorescence architecture via the brassinosteroid signaling pathway.We regard that manipulating the upstream regulatory region of OP1 or genes involved in BR signal pathway could be an efficient way to improve rice inflorescence architecture.
基金jointly funded by National Natural Science Foundation of China(32372206)the Natural Science Foundation of Guangdong Province(2023A1515030224,2023A0505090005,2021TQ06N115)+3 种基金the Governor’s Special Program of 2023(Yuecainong[2023]No.145)the Key Field Research and Development Project of Guangdong Province(2022B0202110003)the Special Fund for Scientific Innovation Strategy-Construction of High Level Academy of Agriculture Science(R2020PY-JX001)Guangdong Key Laboratory of New Technology in Rice Breeding(2023B1212060042)。
文摘In a genome-wide association study,we identified a rice UDP-glycosyltransferase gene,OsUGT706D2,whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid(ABA).OsUGT706D2 positively regulated the biosynthesis of tricin-4’-O-(syringyl alcohol)ether-7-O-glucoside at both the transcriptional and metabolic levels.OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid(ABA)signaling pathway.Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance.ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance.These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.
基金supported by Research Program of Chongqing Municipal Education Commission(KJQN201901127)University Innovation Research Group of Chongqing(CXQT20023)+2 种基金Natural Science Foundation of Chongqing(cstc2021ycjh-bgzxm0184)support by the Research Program of Chongqing Municipal Education Commission(KJQN202201151)National Natural Science Foundation of China(52201107).
文摘LZ91 Mg-Li alloy plates with three types of initial texture were rolled by 70%reduction at both room temperature and 200℃to explore the rolling texture formation ofα-Mg phase.The results showed that the rolling texture is largely affected by the initial texture.All the samples exhibited two main texture components as RD-split double peaks texture and TD-split double peaks texture after large strain rolling.The intensity of the two texture components was strongly influenced by the initial orientation and rolling temperature.Extension twinning altered the large-split non-basal orientation to a near basal one at low rolling strain.The basal orientation induced by twinning is unstable,which finally transmitted to the RD-split texture.The strong TD-split texture formed due to slip-induced orientation transition from its initial orientation.The competition between prismatic and basal slip determined the intensity and tilt angle of the TD-split texture.By increasing the rolling temperature,the TD-split texture component was enhanced in all three samples.Limitation of extension twinning behavior and the promotion of prismatic slip at elevated temperature are the main reasons for the difference in hot and cold rolling texture.
基金Supported by Key R&D Program of Zhejiang,No.2023C03172.
文摘BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.
基金supported by the National Key R&D Program of China(Grant No.:2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(Grant Nos.:2022-I2M-1-028,2022-I2M-2-002,and 2021-I2M-1-007)+1 种基金the National Natural Science Foundation of China(Grant Nos.:81973290 and 82173888)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study,China(Grant No.:Z141102004414062)。
文摘Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
基金the National Natural Science Foundation of China (22108115, 21838004)Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao Young Scholars (21729601)+1 种基金China Postdoctoral Science Foundation funded project (2021M691554)Kempe foundation (SMK21-0020) in Sweden。
文摘Viscous behavior is important for the process design, especially for the non-Newtonian fluid. In this study, the viscous behaviors of slurry, i.e., 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)im ide([Hmim][NTf_(2)])/titanium dioxide(TiO_(2))-polyethylene glycol(PEG200), were determined experimentally and systematically. The pressure drop was estimated when [Hmim][NTf_(2)]/TiO_(2)-PEG200 was used as the solvent in the absorption/desorption towers. The results show that the slurry belongs to the non-Newtonian fluid with shear-thinning behavior. High temperature and low solid content are beneficial to reduce the viscosity of [Hmim][NTf_(2)]/TiO_(2)-PEG200, and the presence of [Hmim][NTf_(2)] can effectively reduce the viscosity of the slurry. In addition, high temperature is preferable for reducing the pressure drop, and the pressure drop of slurry with the solid content value of 8.0%(mass) can reduce by 28.0%when the temperature increases from 313 to 333 K.
文摘Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.
文摘为研究串联发射的弹丸在不同起始速度下动态挤进膛线的力学机理与运动特点,以30 mm火炮为对象分析了串联发射方式的内弹道物理过程,建立了弹丸与坡膛的有限元模型,采用LS-DYNA软件进行了挤进过程的有限元仿真。研究结果表明:挤进过程中,弹带变形规律不受挤进起始速度的影响,均是逐步被膛线刻槽并发生塑性变形;起始速度由5 m·s^(-1)增加至400 m·s^(-1),弹带等效应力峰值从611.8 MPa升高至717.5 MPa,弹带塑性应变最大值从0.89降低至0.75,挤进阻力峰值从为20.3 k N提高至22.9 k N,挤进完成后的摩擦阻力从0提高至3.5 k N,挤进起始速度增加导致了弹带材料应变率、塑性流动应力与挤进阻力的改变,影响弹丸挤进后的内弹道过程;3发弹串联发射时,首发弹20个节点轴向速度的标准差为8.3 m·s^(-1),后续弹分别为18.2,26.7 m·s^(-1),后续弹挤进时的振动冲击效应较首发弹显著。