Partial root-zone irrigation （PRI） has been proved to be an optimal water-saving irrigation technology, however, few studies were done on water transportation and distribution under PRI. The present study was perfor...Partial root-zone irrigation （PRI） has been proved to be an optimal water-saving irrigation technology, however, few studies were done on water transportation and distribution under PRI. The present study was performed to investigate the water transportation and distribution among the wet and dry root-zones and the shoot using deuterium water （D2O） in 1/4 root-zone PRI experiment. It also aimed to determine and analyze the D2O relative abundance within different types of roots and shoots. The results indicated that water could be transported from roots in wet root-zone to roots in dry root-zone and shoots within 2 h after irrigation. Water transportation in roots of wet-zone was carried out by absorbing root, 1-2 mm root, 2-5 mm root, and〉5 mm root progressively, while through a reverse process in three dry root-zones. In shoots, water was transported to trunk, central trunk, annual branches, shoot and leaf progressively. Thus in the young apple trees subjected to PRI, water was distributed ifrst in the roots, including the roots in the wet and dry root-zones, to satisfy the water need of roots itself, and then transported to the shoot within hours of irrigation.展开更多
In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it ...In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it leads to the serious issue of children on waiting lists. Based on the background mentioned above, using statistical method, geographical information system (GIS) and public open data, scenario analysis to select transportation, the present study aimed to propose a method to quantitatively evaluate the current location of childcare facilities in Japanese urban areas. In the present study, the model of the p-median problem used to obtain the optimal location of facilities was modified, and a method to evaluate the current situation concerning the shortage or overage of childcare facilities by district was proposed. As evaluations are conducted using quantitative data such as the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts, the evaluation results are also quantitative, making it an effective indicator for evaluating the locations of childcare facilities. Additionally, the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts were calculated based on public open data. Therefore, the evaluation method in the present study has a high temporal reproducibility as well as spatial reproducibility.展开更多
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b...BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.展开更多
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ d...In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.展开更多
Background： Calcium is a vital mineral and an indispensable component of milk for ruminants. The regulation of transcellular calcium transport by 1,25-dihydroxyvitamin D3 （1,25-（OH）2D3, the active form of vitamin ...Background： Calcium is a vital mineral and an indispensable component of milk for ruminants. The regulation of transcellular calcium transport by 1,25-dihydroxyvitamin D3 （1,25-（OH）2D3, the active form of vitamin D） has been confirmed in humans and rodents, and regulators, including vitamin D receptor （VDR）, calcium binding protein Dgk （calbindin-Dgk）, plasma membrane Ca2＋-ATPase ] b （PMCAlb）, PMAC2b and Oral1, are involved in this process. However, it is still unclear whether 1,25-（OH）2D3 could stimulate calcium transport in the ruminant mammary gland. The present trials were conducted to study the effect of 1,25-（OH）2D3 supplementation and energy availability on the expression of genes and proteins related to calcium secretion in goat mammary epithelial cells. Methods： An in vitro culture method for goat secreting mammary epithelial cells was successfully established. The cells were treated with different doses of 1,25-（OH）2D3 （0, 0.1, 1.0, 10.0 and 100.0 nmol/L） for calcium transport research, followed by a 3-bromopyruvate （3-BrPA, an inhibitor of glucose metabolism） treatment to determine its dependence on glucose availability. Cell proliferation ratios, glucose consumption and enzyme activities were measured with commercial kits, and real-time quantitative polymerase chain reaction （RT-qPCR）, and western blots were used to determine the expression of genes and proteins associated with mammary calcium transport in dairy goats, respectively. Results： 1,25-（OH）2D3 promoted cell proliferation and the expression of genes involved in calcium transport in a dose-dependent manner when the concentration did not exceed 10.0 nmol/L. In addition, 100.0 nmol/L 1,25-（OH） 2D3 inhibited cell proliferation and the expression of associated genes compared with the 10.0 nmol/L treatment. The inhibition of hexokinase 2 （HK2）, a rate-limiting enzyme in glucose metabolism, decreased the expression of PMCA1 b and PMCA2b at the mRNA and protein levels as well as the transcription of Oral1, indicating that glucose avaitability was required for goat mammary calcium transport. The optimal concentration of 1,25-（OH）2D3 that facilitated calcium transport in this study was 10.0 nmol/L. Conclusions： Supplementation with 1,25-（OH）2D3 influenced cell proliferation and regulated the expression of calcium transport modulators in a dose- and energy-dependent manner, thereby highlighting the role of 1,25-（OH）2D3 as an efficacious regulatory agent that produces calcium-enriched milk in ruminants when a suitable energy status was guaranteed.展开更多
The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps3...The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins （SNXs）. Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2＇s dimerization partners, SNX6, interacts with the p150Gued subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50Gued interaction. Disruption of the SNX6-pl50Glued interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.展开更多
基金supported by the Beijing Natural Science Foundation,China (6102006)the New-Star of Science and Technology of Beijing Metropolis,China (2011051)
文摘Partial root-zone irrigation （PRI） has been proved to be an optimal water-saving irrigation technology, however, few studies were done on water transportation and distribution under PRI. The present study was performed to investigate the water transportation and distribution among the wet and dry root-zones and the shoot using deuterium water （D2O） in 1/4 root-zone PRI experiment. It also aimed to determine and analyze the D2O relative abundance within different types of roots and shoots. The results indicated that water could be transported from roots in wet root-zone to roots in dry root-zone and shoots within 2 h after irrigation. Water transportation in roots of wet-zone was carried out by absorbing root, 1-2 mm root, 2-5 mm root, and〉5 mm root progressively, while through a reverse process in three dry root-zones. In shoots, water was transported to trunk, central trunk, annual branches, shoot and leaf progressively. Thus in the young apple trees subjected to PRI, water was distributed ifrst in the roots, including the roots in the wet and dry root-zones, to satisfy the water need of roots itself, and then transported to the shoot within hours of irrigation.
文摘In recent Japan, as there has been an increase of dual-income households and the demand for childcare facilities has especially increased especially in urban areas, childcare facilities and workers are lacking and it leads to the serious issue of children on waiting lists. Based on the background mentioned above, using statistical method, geographical information system (GIS) and public open data, scenario analysis to select transportation, the present study aimed to propose a method to quantitatively evaluate the current location of childcare facilities in Japanese urban areas. In the present study, the model of the p-median problem used to obtain the optimal location of facilities was modified, and a method to evaluate the current situation concerning the shortage or overage of childcare facilities by district was proposed. As evaluations are conducted using quantitative data such as the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts, the evaluation results are also quantitative, making it an effective indicator for evaluating the locations of childcare facilities. Additionally, the specialization coefficient of person trip for transportation and the distance between childcare facilities and districts were calculated based on public open data. Therefore, the evaluation method in the present study has a high temporal reproducibility as well as spatial reproducibility.
基金Supported by National Natural Science Foundation of China,No.82060123Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28+1 种基金Fund Project of Guizhou Provincial Science and Technology Department,No.[2020]1Y299Guizhou Provincial Health Commission,No.gzwjk2019-1-082。
文摘BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.
基金Supported by China Medical University,No.CMU111-MF-10.
文摘In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
基金supported by the National Key Technologies R&D Program of China(2012BAD12B02 and 2012BAD39B05-2)the National Funds for Natural Science of China(31472122)Northwest A&F University Ph.D.Research Start-up funds(Z111021309)
文摘Background： Calcium is a vital mineral and an indispensable component of milk for ruminants. The regulation of transcellular calcium transport by 1,25-dihydroxyvitamin D3 （1,25-（OH）2D3, the active form of vitamin D） has been confirmed in humans and rodents, and regulators, including vitamin D receptor （VDR）, calcium binding protein Dgk （calbindin-Dgk）, plasma membrane Ca2＋-ATPase ] b （PMCAlb）, PMAC2b and Oral1, are involved in this process. However, it is still unclear whether 1,25-（OH）2D3 could stimulate calcium transport in the ruminant mammary gland. The present trials were conducted to study the effect of 1,25-（OH）2D3 supplementation and energy availability on the expression of genes and proteins related to calcium secretion in goat mammary epithelial cells. Methods： An in vitro culture method for goat secreting mammary epithelial cells was successfully established. The cells were treated with different doses of 1,25-（OH）2D3 （0, 0.1, 1.0, 10.0 and 100.0 nmol/L） for calcium transport research, followed by a 3-bromopyruvate （3-BrPA, an inhibitor of glucose metabolism） treatment to determine its dependence on glucose availability. Cell proliferation ratios, glucose consumption and enzyme activities were measured with commercial kits, and real-time quantitative polymerase chain reaction （RT-qPCR）, and western blots were used to determine the expression of genes and proteins associated with mammary calcium transport in dairy goats, respectively. Results： 1,25-（OH）2D3 promoted cell proliferation and the expression of genes involved in calcium transport in a dose-dependent manner when the concentration did not exceed 10.0 nmol/L. In addition, 100.0 nmol/L 1,25-（OH） 2D3 inhibited cell proliferation and the expression of associated genes compared with the 10.0 nmol/L treatment. The inhibition of hexokinase 2 （HK2）, a rate-limiting enzyme in glucose metabolism, decreased the expression of PMCA1 b and PMCA2b at the mRNA and protein levels as well as the transcription of Oral1, indicating that glucose avaitability was required for goat mammary calcium transport. The optimal concentration of 1,25-（OH）2D3 that facilitated calcium transport in this study was 10.0 nmol/L. Conclusions： Supplementation with 1,25-（OH）2D3 influenced cell proliferation and regulated the expression of calcium transport modulators in a dose- and energy-dependent manner, thereby highlighting the role of 1,25-（OH）2D3 as an efficacious regulatory agent that produces calcium-enriched milk in ruminants when a suitable energy status was guaranteed.
基金We thank Yingfang Liu （Institute of Biophysics, Chinese Acad- emy of Sciences） for advice on PX domain structure and SNX6 mutations. We are particularly grateful to Yanmin Yang （Stanford University, USA） for insightful discussions and the Flag-MAP1B LC construct. We also thank Juan S Bonifacino （NIH, USA） for the rabbit anti-CI-MPR antibody, Hiroyoshi Ariga （Hokkaido University, Japan） for Flag- and HA-tagged human SNX6 overexpression constructs, and Li Yu （Tsinghua University, China） for the YFP-EEA1 expression construct. We thank Chonglin Yang （Institute of Genetics and Developmental Biology, Chinese Academy of Sciences）, Dahua Chen （Institute of Zoology, Chinese Academy of Sciences） and Li Yu for critical reading of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （30770675） and Chinese Academy of Sciences （KSCX1-YW-R-37）. J-J Liu is supported by the CAS 100-Tal- ents Program.
文摘The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins （SNXs）. Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2＇s dimerization partners, SNX6, interacts with the p150Gued subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50Gued interaction. Disruption of the SNX6-pl50Glued interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.
