Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in pati...Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival.Moreover,our data suggested that the HNF3γreduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γmRNA.HNF3γexpression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells.Interestingly,HNF3γdelivery promoted differentiation of not only HCC cells but also liver CSCs,which led to suppression of HCC growth.Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules,which could synergistically facilitate HCC cell differentiation.More importantly,enforced HNF3γexpression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression,which are major membrane transporters for sorafenib uptake.Clinical investigation showed that patient-derived HCC xenografts with high HNF3γexpression exhibited a sorafenib response and patients with high HCC HNF3γlevels benefited from sorafenib therapy.Together,these results suggest that HNF3γplays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.展开更多
Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster prot...Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in LIHC.We then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical cohorts.The detailed methods were described in the supplementary material.展开更多
This paper reviews the recent literature on solving the Boolean satisfiability problem(SAT),an archetypal N P-complete problem,with the aid of machine learning(ML)techniques.Over the last decade,the machine learning s...This paper reviews the recent literature on solving the Boolean satisfiability problem(SAT),an archetypal N P-complete problem,with the aid of machine learning(ML)techniques.Over the last decade,the machine learning society advances rapidly and surpasses human performance on several tasks.This trend also inspires a number of works that apply machine learning methods for SAT solving.In this survey,we examine the evolving ML SAT solvers from naive classifiers with handcrafted features to emerging end-to-end SAT solvers,as well as recent progress on combinations of existing conflict-driven clause learning(CDCL)and local search solvers with machine learning methods.Overall,solving SAT with machine learning is a promising yet challenging research topic.We conclude the limitations of current works and suggest possible future directions.The collected paper list is available at https://github.com/ThinklabSJTU/awesome-ml4co.Keywords:Machine learning(ML),Boolean satisfiability(SAT),deep learning,graph neural networks(GNNs),combinatorial optimization.展开更多
The Type-B authentic response regulator(ARR-Bs)gene family is one of the important plant-specific transcription factor families involved in variety of physiological processes.However,study of ARR-Bs gene family in soy...The Type-B authentic response regulator(ARR-Bs)gene family is one of the important plant-specific transcription factor families involved in variety of physiological processes.However,study of ARR-Bs gene family in soybean is limited.Genome-wide analysis and expression profiling of the ARR-Bs gene family were performed in the soybean genome.31 ARR-Bs genes(namely GmARR-B1-31)were identified,containing conserved catalytic domains with protein lengths and molecular weights ranging from 246 to 699 amino acids(aa)and 28.30 to 76.86 kDa,respectively.Phylogenetic analysis grouped ARR-Bs genes into three clusters—Cluster I,Cluster II,and Cluster III—which included 15,12,and 4 genes,respectively,and were asymmetrically distributed on 17 chromosomes.Tissue specific expression analysis of GmARR-Bs family revealed a high transcription level in flowers,roots and seeds.The subcellular localization of GmARR5,GmARR14 were observed in the nucleus,and the promoter region of them included low-temperature responsive element(LTR),the C-repeat/dehydration responsive element(DRE),MBS,ABRE,MYB,MEJA and TCA-elements,which possibly participate in abiotic stress and hormones responses.qRTPCR analysis showed that the expression of GmARR-B genes were affected by different abiotic stresses,especially cold stress and salt stress,and GmARR-B5 and GmARR-B14 were significantly induced by cold stress.This suggested that ARR-Bs genes were involved in multiple abiotic stress response pathways and acted as a positive factor under cold stress.展开更多
Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of...Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of HCC patients is still unsatisfactory due to the frequent relapse and chemoresistance.Accumulating evidence has demonstrated that liver cancer stem cells(CSCs)are critical for HCC chemoresistance and recurrence.Nevertheless,the molecular mechanisms of liver CSC regulation remain unclear,which hampers the development of the therapeutic strategy that targets liver CSCs.展开更多
基金supported by Ministry of Education(MOE)Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer and Shanghai Key Laboratory of Hepatobiliary Tumor Biologysupported by grants from the National Natural Science Foundation of China 81972222,81772582,and 81702736,National Key R&D Program of China(2017YFA0504503)Program of Shanghai Academic Research Leader(18XD1405400).
文摘Hepatocyte nuclear factor 3γ(HNF3γ)is a hepatocyte nuclear factor,but its role and clinical significance in hepatocellular carcinoma(HCC)remain unclear.Herein,we report that HNF3γexpression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival.Moreover,our data suggested that the HNF3γreduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γmRNA.HNF3γexpression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells.Interestingly,HNF3γdelivery promoted differentiation of not only HCC cells but also liver CSCs,which led to suppression of HCC growth.Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules,which could synergistically facilitate HCC cell differentiation.More importantly,enforced HNF3γexpression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression,which are major membrane transporters for sorafenib uptake.Clinical investigation showed that patient-derived HCC xenografts with high HNF3γexpression exhibited a sorafenib response and patients with high HCC HNF3γlevels benefited from sorafenib therapy.Together,these results suggest that HNF3γplays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.
基金supported by the Program of the Shanghai Key Laboratory of Cell Engineering 14DZ2272300 from the Science and Technology Commission of Shanghai Municipality。
文摘Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in LIHC.We then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical cohorts.The detailed methods were described in the supplementary material.
基金supported by National Key Research and Development Program of China(No.2020AAA0107600)National Science Foundation of China(No.62102258)+2 种基金Shanghai Pujiang Program,China(No.21PJ1407300)Shanghai Municipal Science and Technology Major Project,China(No.2021SHZDZX0102)Science and Technology Commission of Shanghai Municipality Project,China(No.22511105100),and also sponsored by Huawei Ltd,China.
文摘This paper reviews the recent literature on solving the Boolean satisfiability problem(SAT),an archetypal N P-complete problem,with the aid of machine learning(ML)techniques.Over the last decade,the machine learning society advances rapidly and surpasses human performance on several tasks.This trend also inspires a number of works that apply machine learning methods for SAT solving.In this survey,we examine the evolving ML SAT solvers from naive classifiers with handcrafted features to emerging end-to-end SAT solvers,as well as recent progress on combinations of existing conflict-driven clause learning(CDCL)and local search solvers with machine learning methods.Overall,solving SAT with machine learning is a promising yet challenging research topic.We conclude the limitations of current works and suggest possible future directions.The collected paper list is available at https://github.com/ThinklabSJTU/awesome-ml4co.Keywords:Machine learning(ML),Boolean satisfiability(SAT),deep learning,graph neural networks(GNNs),combinatorial optimization.
基金This work was financially supported by the National Modern Agricultural Industrial Technology System(CARS-04-01A).
文摘The Type-B authentic response regulator(ARR-Bs)gene family is one of the important plant-specific transcription factor families involved in variety of physiological processes.However,study of ARR-Bs gene family in soybean is limited.Genome-wide analysis and expression profiling of the ARR-Bs gene family were performed in the soybean genome.31 ARR-Bs genes(namely GmARR-B1-31)were identified,containing conserved catalytic domains with protein lengths and molecular weights ranging from 246 to 699 amino acids(aa)and 28.30 to 76.86 kDa,respectively.Phylogenetic analysis grouped ARR-Bs genes into three clusters—Cluster I,Cluster II,and Cluster III—which included 15,12,and 4 genes,respectively,and were asymmetrically distributed on 17 chromosomes.Tissue specific expression analysis of GmARR-Bs family revealed a high transcription level in flowers,roots and seeds.The subcellular localization of GmARR5,GmARR14 were observed in the nucleus,and the promoter region of them included low-temperature responsive element(LTR),the C-repeat/dehydration responsive element(DRE),MBS,ABRE,MYB,MEJA and TCA-elements,which possibly participate in abiotic stress and hormones responses.qRTPCR analysis showed that the expression of GmARR-B genes were affected by different abiotic stresses,especially cold stress and salt stress,and GmARR-B5 and GmARR-B14 were significantly induced by cold stress.This suggested that ARR-Bs genes were involved in multiple abiotic stress response pathways and acted as a positive factor under cold stress.
基金This work was supported by the grants from the National Key Research and Developm ent Program of China 2017YFA0504503National Natural Science Foundation of China(NSFC)81972777 and 82003161+3 种基金Program of Shanghai Academ ic Research Leader(18XD1405400)Natural Science Foundation of Shanghai(20ZR145770)the Shanghai Key Laboratory of Cell Engineering(14DZ2272300)Shanghai Sailing Project(20YF1459600)from the Science and Technology Commission of Shanghai Municipality.
文摘Dear Editor,Hepatocellular carcinoma(HCC),the most common pathological type of primary liver cancer,ranks as the third deadliest cancer.Despite the progress of surgical resection in recent years,the 5-year survival of HCC patients is still unsatisfactory due to the frequent relapse and chemoresistance.Accumulating evidence has demonstrated that liver cancer stem cells(CSCs)are critical for HCC chemoresistance and recurrence.Nevertheless,the molecular mechanisms of liver CSC regulation remain unclear,which hampers the development of the therapeutic strategy that targets liver CSCs.
