BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proli...BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.展开更多
BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin co...BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)activation.Previous studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney injury.However,the effects of BT2 on ulcerative colitis(UC)are unknown.AIM To investigate the anti-UC effects of BT2 and the underlying mechanism.METHODS Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 d.The mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day 7.At the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical assays.Cytokine levels were measured by flow cytometry.The contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.RESULTS Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice.BT2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 level.In addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice.Furthermore,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis.Compared with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella.CONCLUSION Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.展开更多
A water-soluble macrocycle that bears four carboxylate anions has been designed and prepared,which forms a rectangular cavity that can efficiently encapsulate discrete electron-deficient aromatic compounds,including b...A water-soluble macrocycle that bears four carboxylate anions has been designed and prepared,which forms a rectangular cavity that can efficiently encapsulate discrete electron-deficient aromatic compounds,including berberine and palmatine.This macrocycle is revealed to be highly biocompatible and able to inhibit the bitter taste of the two drugs.展开更多
There are generally four recognized classes of japonica rice cultivars grown in the lower region of the Yangtze River valley. The geographical distribution of the four classes is latitude-dependent. Variation for head...There are generally four recognized classes of japonica rice cultivars grown in the lower region of the Yangtze River valley. The geographical distribution of the four classes is latitude-dependent. Variation for heading date （HD） among 29 japonica rice cultivars grown in the lower region of the Yangtze River valley and belonging to the four classes was characterized, and their sensitivity to variations in photoperiod and temperature was analyzed. All of the cultivars were sensitive to both photoperiod and temperature. A regression analysis showed that HD is closely correlated with photoperiod sensitivity （PS）. The PS of the four classes increased gradually from the medium maturing middle （MMM） types, through the late maturing middle （LMM） and early maturing late （EML） types to the medium maturing late （MML） types. Crosses with tester lines established that almost all of the cultivars carry the dominant early-heading allele at Ef-1, the photoperiod insensitive allele e2 and the PS alleles E1 or E1^t. Most of the MMM, LMM and MML types carry the insensitive allele e3, while EML types have either E3 or E3^t. At Se-1, MMM and LMM types have Se-1^e, some EML types have Se-1^e and others Se-1^n, while the MML types are mostly Se-fn. The PS of some MMM, LMM and EML types is reduced by the presence of hd2. These results show that the distribution of the four rice cultivar classes from high latitude to low latitude regions depended on a gradual increase in PS, which is mainly determined by its HD genotypes.展开更多
Middle indica cultivars are planted in the middle to lower regions of the Yangtze River. Hybrid combinations with these cultivars have a high yield potential but the presence of late-transgressive-segregants limits th...Middle indica cultivars are planted in the middle to lower regions of the Yangtze River. Hybrid combinations with these cultivars have a high yield potential but the presence of late-transgressive-segregants limits the further exploitation of heterosis. To understand the genetic basis of the heading date in these middle maturing cultivars, we carried out a genetic analysis of 10 typical middle-season cultivars using a number of heading date isogenic lines under both long and short day conditions. The results showed that Teqing, 752, CDR22, Bo B, 9311 and 11-32B carry two photoperiod sensitive genes E1 or Se.1 and E3, and Teqing, 752 and CDR22 carry a dominant early-heading gene Ef-1 while Bo B, 9311 and 11-32B carry a recessive late-heading gene ef-1. Based on the findings of the present and previous works on Guichao 2, Minghui 63, Nanjing 11 and Pei＇ai64S, it was concluded that all of these middle indica cultivars carried the recessive allele hd2, which could inhibit the expression of El or Se.1, and they formed rational combinations of genotype for heading date during a long period of evolution. The effects of the different combinations of genotype for heading date on rice cultivation and extension were discussed, and genetic basis of broad adaptability of hybrid middle indica cultivars was analyzed.展开更多
II-32A, an elite male-sterile line of rice （Oryza sativa L.）, has been widely used for the production of hybrid rice seed In China. Heading date In most combinations using II-32A shows transgressive Inheritance or s...II-32A, an elite male-sterile line of rice （Oryza sativa L.）, has been widely used for the production of hybrid rice seed In China. Heading date In most combinations using II-32A shows transgressive Inheritance or similarity to the latter parent, but the genotype of II-32A with respect to major genes for heading time Is unknown. This limits the further exploitation of this sterile line In breeding and hybrid seed production. Using a number of major gene heading date Isogenlc lines and heading date QTL near-lsogenic lines, we genetically analyzed II-32B under both long- and short-day conditions. We show that II-32B carries two photoperlod-sensltlve genes, E1 and E3, a recessive late-heading gene, ef-l, and a photoperlod-sensltlve allele, Se-1^u. In addition we Identified In II- 32B a recessive Inhibitor for E1 or Se-1^n and other modified photoperlod-sensltlve genes. The heading-date constitution of II-32A was determined to be E1e2E3Se-1^uef-li-Se-1.展开更多
A record-breaking heavy rainfall swept across Suizhou of Hubei province in China on August 12,2021.It was characterized by suddenness and extremeness and caused severe socio-economic losses.To deepen the understanding...A record-breaking heavy rainfall swept across Suizhou of Hubei province in China on August 12,2021.It was characterized by suddenness and extremeness and caused severe socio-economic losses.To deepen the understanding of such an urban rainstorm and to improve the forecasting ability,this study revealed the dominant atmospheric circulation and moisture sources for this event.We performed a Lagrangian model FLEXPART to understand this event in terms of moisture sources and transport trajectories.Three key circulation systems affecting this extreme event were identified,including the western Pacific subtropical high(WPSH),the low-level southwesterly jet and an anticyclone over northern China.The low-level jet was lifted along the northern dry and cold air mass to form a front,resulting in the heavy rain.The moisture sources located on land contributed about 64%of the moisture.The development of the low-level southwesterly jet in southern China was strengthened near the time of the precipitation occurrence,providing the main moisture supply.Southern China(23°-32.5°N,98°-122°E)was the most important source region,which contributed the most to the precipitation(43.6%).The results highlight the prominent role of the terrestrial water cycle in this extreme precipitation event over Hubei.展开更多
基金The Science and Technology Commission of Shanxi province,No.201901D111428.
文摘BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.
基金Supported by National Natural Science Foundation of ChinaNo. 82074241+1 种基金Project of Jiangsu Province Hospital of Traditional Chinese Medicine Peak TalentNo. y2021rc36
文摘BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)activation.Previous studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney injury.However,the effects of BT2 on ulcerative colitis(UC)are unknown.AIM To investigate the anti-UC effects of BT2 and the underlying mechanism.METHODS Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 d.The mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day 7.At the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical assays.Cytokine levels were measured by flow cytometry.The contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.RESULTS Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice.BT2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 level.In addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice.Furthermore,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis.Compared with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella.CONCLUSION Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.
基金the National Natural Science Foundation of China(Nos.22271059,21921003,21890730 and 21890732)for financial support.
文摘A water-soluble macrocycle that bears four carboxylate anions has been designed and prepared,which forms a rectangular cavity that can efficiently encapsulate discrete electron-deficient aromatic compounds,including berberine and palmatine.This macrocycle is revealed to be highly biocompatible and able to inhibit the bitter taste of the two drugs.
基金Supported by the National Hi-Tech Research and Development Programof China (2006AA100101,2006BAD01A01-5 and 2006BAD13B01)the National Natural Science Foundation of China (30871497)+2 种基金Jiangsu Scienceand Technology Development Program (BG2006301)Jiangsu Agricultural Germplasm Gene Pool Program (sx(2008)g08)the 111 Project (B08025)
文摘There are generally four recognized classes of japonica rice cultivars grown in the lower region of the Yangtze River valley. The geographical distribution of the four classes is latitude-dependent. Variation for heading date （HD） among 29 japonica rice cultivars grown in the lower region of the Yangtze River valley and belonging to the four classes was characterized, and their sensitivity to variations in photoperiod and temperature was analyzed. All of the cultivars were sensitive to both photoperiod and temperature. A regression analysis showed that HD is closely correlated with photoperiod sensitivity （PS）. The PS of the four classes increased gradually from the medium maturing middle （MMM） types, through the late maturing middle （LMM） and early maturing late （EML） types to the medium maturing late （MML） types. Crosses with tester lines established that almost all of the cultivars carry the dominant early-heading allele at Ef-1, the photoperiod insensitive allele e2 and the PS alleles E1 or E1^t. Most of the MMM, LMM and MML types carry the insensitive allele e3, while EML types have either E3 or E3^t. At Se-1, MMM and LMM types have Se-1^e, some EML types have Se-1^e and others Se-1^n, while the MML types are mostly Se-fn. The PS of some MMM, LMM and EML types is reduced by the presence of hd2. These results show that the distribution of the four rice cultivar classes from high latitude to low latitude regions depended on a gradual increase in PS, which is mainly determined by its HD genotypes.
基金Supported by the High-Tech Research and Development(863) Program of Chinathe National Natural Science Foundation of China(30571142)the High Technology Program of Jiangsu Province(BG2004303 and BG2006301) and PCSIRT
文摘Middle indica cultivars are planted in the middle to lower regions of the Yangtze River. Hybrid combinations with these cultivars have a high yield potential but the presence of late-transgressive-segregants limits the further exploitation of heterosis. To understand the genetic basis of the heading date in these middle maturing cultivars, we carried out a genetic analysis of 10 typical middle-season cultivars using a number of heading date isogenic lines under both long and short day conditions. The results showed that Teqing, 752, CDR22, Bo B, 9311 and 11-32B carry two photoperiod sensitive genes E1 or Se.1 and E3, and Teqing, 752 and CDR22 carry a dominant early-heading gene Ef-1 while Bo B, 9311 and 11-32B carry a recessive late-heading gene ef-1. Based on the findings of the present and previous works on Guichao 2, Minghui 63, Nanjing 11 and Pei＇ai64S, it was concluded that all of these middle indica cultivars carried the recessive allele hd2, which could inhibit the expression of El or Se.1, and they formed rational combinations of genotype for heading date during a long period of evolution. The effects of the different combinations of genotype for heading date on rice cultivation and extension were discussed, and genetic basis of broad adaptability of hybrid middle indica cultivars was analyzed.
文摘II-32A, an elite male-sterile line of rice （Oryza sativa L.）, has been widely used for the production of hybrid rice seed In China. Heading date In most combinations using II-32A shows transgressive Inheritance or similarity to the latter parent, but the genotype of II-32A with respect to major genes for heading time Is unknown. This limits the further exploitation of this sterile line In breeding and hybrid seed production. Using a number of major gene heading date Isogenlc lines and heading date QTL near-lsogenic lines, we genetically analyzed II-32B under both long- and short-day conditions. We show that II-32B carries two photoperlod-sensltlve genes, E1 and E3, a recessive late-heading gene, ef-l, and a photoperlod-sensltlve allele, Se-1^u. In addition we Identified In II- 32B a recessive Inhibitor for E1 or Se-1^n and other modified photoperlod-sensltlve genes. The heading-date constitution of II-32A was determined to be E1e2E3Se-1^uef-li-Se-1.
基金Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0102)Chinese Academy of Sciences under grant from K.C.Wong Education Foundation。
文摘A record-breaking heavy rainfall swept across Suizhou of Hubei province in China on August 12,2021.It was characterized by suddenness and extremeness and caused severe socio-economic losses.To deepen the understanding of such an urban rainstorm and to improve the forecasting ability,this study revealed the dominant atmospheric circulation and moisture sources for this event.We performed a Lagrangian model FLEXPART to understand this event in terms of moisture sources and transport trajectories.Three key circulation systems affecting this extreme event were identified,including the western Pacific subtropical high(WPSH),the low-level southwesterly jet and an anticyclone over northern China.The low-level jet was lifted along the northern dry and cold air mass to form a front,resulting in the heavy rain.The moisture sources located on land contributed about 64%of the moisture.The development of the low-level southwesterly jet in southern China was strengthened near the time of the precipitation occurrence,providing the main moisture supply.Southern China(23°-32.5°N,98°-122°E)was the most important source region,which contributed the most to the precipitation(43.6%).The results highlight the prominent role of the terrestrial water cycle in this extreme precipitation event over Hubei.
