BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic c...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic chemotherapy,targeted therapies,and immune checkpoint inhibitors have demonstrated synergistic effects in converting unresectable ICC to resectable status and improving patient survival.CASE SUMMARY A 39-year-old male presented with unresectable stage IIIB ICC(cT3N1M0),abdominal pain,and elevated carbohydrate antigen(CA)19-9 levels.He received tri-modal therapy consisting of gemcitabine-oxaliplatin hepatic arterial infusion chemotherapy(GEMOX-HAIC),lenvatinib(8 mg daily),and toripalimab(160 mg every three weeks).After five cycles,significant tumor shrinkage and normalization of CA19-9 levels enabled a left hepatectomy.Complications,including biliary stenosis and liver abscesses,were managed with biliary stenting and percutaneous drainage,which allowed for the continuation of chemotherapy.Postoperative pathological examination confirmed a pathological complete response.At the last follow-up,the patient had maintained 29 months of diseasefree survival post-resection and was continuing postoperative therapy.CONCLUSION This case highlights the potential of a tri-modal therapy combining GEMOX-HAIC,lenvatinib,and toripalimab to convert unresectable ICC to a resectable status,thereby potentially improving patient survival by surgical resection.Further clinical trials investigating this regimen are warranted.展开更多
This study investigates the effectiveness of salicylate(SAL)as an electrolyte additive on the discharge behavior of high-purity(HP)Mg anode in an aqueous half-cell system,using an integrated approach of mathematical m...This study investigates the effectiveness of salicylate(SAL)as an electrolyte additive on the discharge behavior of high-purity(HP)Mg anode in an aqueous half-cell system,using an integrated approach of mathematical modeling and experimental analysis.A finite elementbased model is developed to elucidate the key mechanisms by which SAL influences the voltage profile and pH.Systematic electrochemical measurements,especially intermittent discharge tests combined with electrochemical impedance spectroscopy(EIS),demonstrate that SAL can enhance initial voltage stability of HP Mg anode.Moreover,the model incorporates the SAL-Mg complexation factor to describe the role of SAL in modifying the deposit film on HP Mg surface.The agreement between model predictions and experimental observations suggests that SAL facilitates the formation of compact Mg(OH)_(2) deposits and sustains a favorable pH environment within the half-cell compartment.This integrated approach provides new insights into understanding and optimizing additive effects for Mg-air batteries.展开更多
Crude fat is an important nutritional component of maize kernels.However,the genetic mechanisms underlying crude fat content in maize kernels remain elusive.Previous studies used single-model genome-wide association s...Crude fat is an important nutritional component of maize kernels.However,the genetic mechanisms underlying crude fat content in maize kernels remain elusive.Previous studies used single-model genome-wide association studies(GWAS)with limited population sizes,which can result in false loci positives and hinder functional gene identification.Therefore,this study used a population consisting of 495 maize inbred lines,combined with 1.25 million single nucleotide polymorphisms(SNPs),and implemented GWAS using six models to identify quantitative trait nucleotides(QTNs)controlling crude fat content and to mine key genes.The results revealed a wide variation in crude fat content(0.62-16.03%)and broad-sense heritability(H^(2))(96.23%).In total,744 significant QTNs were detected,with 147 co-located across different models,environments,and methods.Based on the 147 colocated QTNs,candidate genes were searched at 50 kb up-and down-stream intervals of each QTN.We finally screened eight candidate genes(GRMZM2G169089,GRMZM2G117935,GRMZM2G002075,GRMZM2G368838,GRMZM2G058496,GRMZM2G090669,GRMZM2G001241,and GRMZM2G333454)related to crude fat content that exhibited high expression levels during kernel development in maize inbred line B73.Notably,GRMZM2G169089,GRMZM2G117935,GRMZM2G002075,and GRMZM2G368838 are involved in the linoleic acid metabolic pathway,oil metabolism,kernel growth,and development in maize.Furthermore,co-expression network analysis revealed that the eight candidate genes strongly correlated with 30 known genes.Proteins encoded by candidate genes interact with other proteins and play an important role in oil content and oleic acid metabolism in maize kernels.The best haplotypes of candidate genes might increase crude fat content without decreasing maize yield.These results broaden the understanding of the genetic mechanism of crude fat content and facilitate marker-assisted selection for high-crude fat breeding programs for maize.展开更多
Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown ...Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown to facilitate cancer progression by modulating oncogenic variants.However,its specific role and underlying mechanisms in hepatocellular carcinoma(HCC)remain to be elucidated.Methods:PTBP1 expression was evaluated in HCC tissues and cell lines.Subsequently,cells were transfected with vectors designed for PTBP1 overexpression or downregulation.The biological function of PTBP1 was assessed in vitro and in vivo using MTS assays,colony formation assays,transwell assays,xenograft formation,tail vein injection,and orthotopic models.Transcriptome analysis was conducted to elucidate the underlying molecular mechanisms.Results:Our findings demonstrated that PTBP1 exhibited elevated expression in HCC cell lines and tissues.Furthermore,its expression positively correlated with overall and disease-free survival rates,as well as tumor grade and stage.PTBP1 knockdown reduced HCC cell proliferation,migration,and invasion in vitro and suppressed hepatocarcinoma xenograft growth and infiltration in vivo.RNA sequencing(RNA-Seq)analysis identified the AS events associated with PTBP1.PTBP1 functionally enhanced cell proliferation,invasion,and migration by modulating the AS of the microtubule-associated protein tau(MAPT)gene and promoting oncogene expression.Notably,the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC.Conclusions:PTBP1-guided AS of the MAPT gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.展开更多
Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify ...Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE.Data sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.Results: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.展开更多
Smelting activities pose serious environmental problems due to the local and regional heavy metal pollution in soils they cause. It is therefore important to understand the pollution situation and its source in the co...Smelting activities pose serious environmental problems due to the local and regional heavy metal pollution in soils they cause. It is therefore important to understand the pollution situation and its source in the contaminated soils. In this paper, data on heavy metal pollution in soils resulting from Pb/Zn smelting(published in the last 10 years) in China was summarized. The heavy metal pollution was analyzed from a macroscopic point of view. The results indicated that Pb, Zn, As and Cd were common contaminants that were present in soils with extremely high concentrations. Because of the extreme carcinogenicity, genotoxicity and neurotoxicity that heavy metals pose, remediation of the soils contaminated by smelting is urgently required. The primary anthropogenic activities contributing to soil pollution in smelting areas and the progressive development of accurate source identification were performed. Due to the advantages of biominerals, the potential of biomineralization for heavy metal contaminated soils was introduced. Furthermore, the prospects of geochemical fraction analysis, combined source identification methods as well as several optimization methods for biomineralization are presented, to provide a reference for pollution investigation and remediation in smelting contaminated soils in the future.展开更多
OBJECTIVE To study the effect of transforming growth factor β1 （TGF-β1） on differentiation of rhabdomyosarcoma （RMS） cells METHODS RD （human embryonal RMS cell line） cells, cultured in differentiation medium c...OBJECTIVE To study the effect of transforming growth factor β1 （TGF-β1） on differentiation of rhabdomyosarcoma （RMS） cells METHODS RD （human embryonal RMS cell line） cells, cultured in differentiation medium containing 9-cis retinoic acid （9CRA）, were treated with TGF-β1. Proliferation of the cells was examined by the MTT assay. The differentiation specific proteins （sarcomeric actin and MyHC） and myogenic transcription factors （MyoD1 and myogenin） in the RD cells were assessed by immunofluorescence staining. RESULTS Compared to control cells, treatment with lower concentrations of TGF-β1 （0.1 and 0.2 ng/ml） induced an increase in OD values after 4 d （P〈0.01）, whereas higher concentrations of TGF-β1 （2 and 5 ng/ml） led to a reduction of cell viability （P〈0.01）. After exposure to 9CRA, the viability of the cells decreased significantly （P〈0.01）, while sarcomeric actin, MyHC and myogenin were induced. These changes were antagonized by TGF-β1 （0.1 ng/ml）. No changes were observed in expression of MyoD1. CONCLUSION The RMS cells, derived from myogenic progenitors are committed to a myogenic fate, but are arrested in the differentiation course by the addition of TGF-β1 which represses some of the myogenic transcription factors.展开更多
The load-bearing performance(LBP)of pumpable supports(PPS)is crucial for the stability of longwall pre-driven recovery room(PRR)surrounding rock.However,the unbalanced bearing coefficient(UBC)of the PPS(undertaking un...The load-bearing performance(LBP)of pumpable supports(PPS)is crucial for the stability of longwall pre-driven recovery room(PRR)surrounding rock.However,the unbalanced bearing coefficient(UBC)of the PPS(undertaking unequal load along the mining direction)has not been investigated.A mechanical model of the PRR was established,considering the main roof cantilever beam structure,to derive an assessment formula for the load,the failure criteria,and the UBC of the PPS.Subsequently,the generation mechanisms,and influencing factors of the UBC were revealed.Global sensitivity analysis shows that the main roof hanging length(l_(2))and the spacing between the PPS(r)significantly impact the UBC.A novel design of the PPS and the coupling control technology were proposed and applied to reduce the UBC of the PPS in the adjacent longwall PRR.Monitor results showed no failure of the PPS at the test site,with the UBC(ζ)reduced to 1.1 consistent with the design value(1.15)basically,fully utilizing the collaborative LBP of the PPS.Finally,the maximum roof-to-floor convergence of the PRR was 234 mm,effectively controlling the stability of the surrounding rock of the PRR and ensuring the mining equipment recovery.展开更多
The voltage drop appearing at Mg anode-electrolyte interface is a critical issue for the battery power and energy density of aqueous primary Mg-air batteries.The respective voltage loss is typically assigned to the de...The voltage drop appearing at Mg anode-electrolyte interface is a critical issue for the battery power and energy density of aqueous primary Mg-air batteries.The respective voltage loss is typically assigned to the deposits layer forming on the anode surface during discharge.In this work,we experimentally and computationally investigate the critical factors affecting the voltage drop at Mg anode towards a deeper understanding of the contribution of deposit and its growth.A two-dimensional(2D)mathematical model is proposed to compute the voltage drop of Mg-0.15Ca wt.%alloy(Mg-0.15Ca)by means of a semi-empirical formulas and experiments-based modification model,considering the effect of discharge current density,the negative difference effect(NDE)and surface deposits layer itself.This model is utilized to simulate the discharge potential of the anode at predefined experimental current densities.The computed voltage drop(half-cell voltage)is in good agreement with the experimental value.The applicability of the mathematical model is successfully validated on the second material(namely high-purity Mg).展开更多
Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search ...Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.展开更多
In multi-seam mining,the interlayer rock strata between the upper coal seam(UCS)and the lower coal seam(LCS)appear damage and strength weakening after mining the UCS.Ground stability control of the gob-side entry reta...In multi-seam mining,the interlayer rock strata between the upper coal seam(UCS)and the lower coal seam(LCS)appear damage and strength weakening after mining the UCS.Ground stability control of the gob-side entry retaining(GER)under the gob with close distance coal seams(CDCS)is faced with difficulties due to little attention to GER under this condition.This paper focuses on surrounding rock stability control and technical parameters design for GER under the gob with CDCS.The floor rock strata damage characteristics after mining the UCS is first evaluated and the damage factor of the interlayer rock strata below the UCS is also determined.Then,a structural mechanics model of GER surrounding rock is set up to obtain the main design parameters of the side-roadway backfill body(SBB)including the maximum and minimum SBB width calculation formula.The optimal SBB width and the water-to-cement ratio of high water quick-setting material(HWQM)to construct the SBB are determined as 1.2 m and 1.5:1.0,respectively.Finally,engineering trial tests of GER are successfully carried out at#5210 track transportation roadway of Xingwu Colliery.Research results can guide GER design under similar mining and geological conditions.展开更多
Smelting activities are the main pathway for the anthropogenic release of heavy metals(HMs)into the soil-groundwater environment.It is vital to identify the factors affecting HMs pollution to better prevent and manage...Smelting activities are the main pathway for the anthropogenic release of heavy metals(HMs)into the soil-groundwater environment.It is vital to identify the factors affecting HMs pollution to better prevent and manage soil pollution.The present study conducted a comprehensive investigation of HMs in soil from a large abandoned Zn smelting site.An integrated approach was proposed to classify and quantify the factors affecting HMs pollution in the site.Besides,the quantitative relationship between hydrogeological characteristics,pollution transmission pathways,smelting activities and HMs pollutionwas established.Results showed that the soils were highly contaminated by HMs with a pollution index trend of As>Zn>Cd>Pb>Hg.In identifying the pollution hotspots,we conclude that the pollution hotspots of Pb,As,Cd,and Hg present a concentrated distribution pattern.Geo-detector method results showed that the dominant driving factors for HMs distribution and accumulation were the potential pollution source and soil permeability.Additionally,the main drivers are variable for different HMs,and the interaction among factors also enhanced soil HMs contamination.Our analysis illustrates how the confounding influences from complex environmental factors can be distilled to identify key factors in pollution formation to guide future remediation strategies.展开更多
The corrosion performances of the as-cast and solution-treated Mg-0.5Zn samples were investigated in 0.9%Na Cl solution and compared.From the electrochemical measurement results and corrosion morphology observations,i...The corrosion performances of the as-cast and solution-treated Mg-0.5Zn samples were investigated in 0.9%Na Cl solution and compared.From the electrochemical measurement results and corrosion morphology observations,it is found that the corrosion resistance of Mg-0.5Zn deteriorated with the extension of solution treatment duration.The main reason was the formation of Fe-Si precipitates with higher Fe concentrations during heat treatment.The Fe-Si precipitates,especially the ones with high Fe contents influenced the corrosion initiation and propagation significantly.In regard of corrosion performance,the solution-treated and then extruded sample was also performing not as good as the cast and then directly extruded sample.展开更多
The Small ubiquitin-related modifier （SUMO） conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investiga...The Small ubiquitin-related modifier （SUMO） conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investigate in vivo biological function of SUMO paralogs, we inactivated them in the early development of zebrafish. While zebrafish embryos deficient for all three SUMO paralogs, as Ubc9-deficient ones, displayed severe defects, loss of individual SUMO paralog was compatible with a normal development. SUMO-deficient embryos can be rescued by a single human or zebrafish SUMO. While key structural basic lysine residues and N-terminal unstructured stretch of SUMO are critical for in vivo rescue, the consensus Kll sumoylation site of SUMO2 is dispensable, implying that chain formation on this potential site is unessential for normal development. Inactivation of all three SUMOs triggered p53- dependent apoptosis and further inactivation of p53 restored normal zebrafish development. Interestingly, we also demonstrate that the dominant negative truncated form of p53, Δ113p53, significantly blunts SUMO depletion-induced p53 activity in vivo. Taken together, our results suggest that SUMO paralogs are indispensable, but redundant, in the early development of zebrafish.展开更多
基金Supported by Shenzhen Clinical Research Center for Gastroenterology(Gastrointestinal Surgery),No.LCYSSQ20220823091203008.
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is an aggressive malignancy with limited treatment options and a poor prognosis,particularly in unresectable or metastatic cases.Tri-modal strategies combining systemic chemotherapy,targeted therapies,and immune checkpoint inhibitors have demonstrated synergistic effects in converting unresectable ICC to resectable status and improving patient survival.CASE SUMMARY A 39-year-old male presented with unresectable stage IIIB ICC(cT3N1M0),abdominal pain,and elevated carbohydrate antigen(CA)19-9 levels.He received tri-modal therapy consisting of gemcitabine-oxaliplatin hepatic arterial infusion chemotherapy(GEMOX-HAIC),lenvatinib(8 mg daily),and toripalimab(160 mg every three weeks).After five cycles,significant tumor shrinkage and normalization of CA19-9 levels enabled a left hepatectomy.Complications,including biliary stenosis and liver abscesses,were managed with biliary stenting and percutaneous drainage,which allowed for the continuation of chemotherapy.Postoperative pathological examination confirmed a pathological complete response.At the last follow-up,the patient had maintained 29 months of diseasefree survival post-resection and was continuing postoperative therapy.CONCLUSION This case highlights the potential of a tri-modal therapy combining GEMOX-HAIC,lenvatinib,and toripalimab to convert unresectable ICC to a resectable status,thereby potentially improving patient survival by surgical resection.Further clinical trials investigating this regimen are warranted.
基金the China Scholarship Council for the award of fellowship and funding No.201908510177 and No.202106050030supported by dtec.bw–Digitalization and Technology Research Center of the Bundeswehr which Dr.Deng gratefully acknowledges project DMF+1 种基金the AMABML project founded by the Zentrum für Hochleistungs-materialien(ZHM)DEZAIN project for financial support via grant from GIF,the German-Israeli Foundation for Scientific Research and Development.
文摘This study investigates the effectiveness of salicylate(SAL)as an electrolyte additive on the discharge behavior of high-purity(HP)Mg anode in an aqueous half-cell system,using an integrated approach of mathematical modeling and experimental analysis.A finite elementbased model is developed to elucidate the key mechanisms by which SAL influences the voltage profile and pH.Systematic electrochemical measurements,especially intermittent discharge tests combined with electrochemical impedance spectroscopy(EIS),demonstrate that SAL can enhance initial voltage stability of HP Mg anode.Moreover,the model incorporates the SAL-Mg complexation factor to describe the role of SAL in modifying the deposit film on HP Mg surface.The agreement between model predictions and experimental observations suggests that SAL facilitates the formation of compact Mg(OH)_(2) deposits and sustains a favorable pH environment within the half-cell compartment.This integrated approach provides new insights into understanding and optimizing additive effects for Mg-air batteries.
基金supported by the National Natural Science Foundation of China(32101700)the China Postdoctoral Science Foundation(2022M7111220)+1 种基金the Science and Technology Innovation Program of Hunan Province,China(2021RC2082)and the Postgraduate Scientific Research Innovation Project of Hunan Province,China(CX20230697)。
文摘Crude fat is an important nutritional component of maize kernels.However,the genetic mechanisms underlying crude fat content in maize kernels remain elusive.Previous studies used single-model genome-wide association studies(GWAS)with limited population sizes,which can result in false loci positives and hinder functional gene identification.Therefore,this study used a population consisting of 495 maize inbred lines,combined with 1.25 million single nucleotide polymorphisms(SNPs),and implemented GWAS using six models to identify quantitative trait nucleotides(QTNs)controlling crude fat content and to mine key genes.The results revealed a wide variation in crude fat content(0.62-16.03%)and broad-sense heritability(H^(2))(96.23%).In total,744 significant QTNs were detected,with 147 co-located across different models,environments,and methods.Based on the 147 colocated QTNs,candidate genes were searched at 50 kb up-and down-stream intervals of each QTN.We finally screened eight candidate genes(GRMZM2G169089,GRMZM2G117935,GRMZM2G002075,GRMZM2G368838,GRMZM2G058496,GRMZM2G090669,GRMZM2G001241,and GRMZM2G333454)related to crude fat content that exhibited high expression levels during kernel development in maize inbred line B73.Notably,GRMZM2G169089,GRMZM2G117935,GRMZM2G002075,and GRMZM2G368838 are involved in the linoleic acid metabolic pathway,oil metabolism,kernel growth,and development in maize.Furthermore,co-expression network analysis revealed that the eight candidate genes strongly correlated with 30 known genes.Proteins encoded by candidate genes interact with other proteins and play an important role in oil content and oleic acid metabolism in maize kernels.The best haplotypes of candidate genes might increase crude fat content without decreasing maize yield.These results broaden the understanding of the genetic mechanism of crude fat content and facilitate marker-assisted selection for high-crude fat breeding programs for maize.
基金supported by the National Natural Science Foundation of China(Nos.81972771,82173062)the Key Areas Project of Education Department of Guangdong Province(No.2021ZDZX2017)+3 种基金the Tertiary Education Scientific Research Project of Guangzhou Municipal Education Bureau(No.202235387)the Guangzhou Science and Technology Project of Guangzhou Municipal Science and Technology Bureau(No.2023A03J0428)the Natural Science Foundation of Guangdong Province,China(No.2024A1515013082)the Guangdong Basic and Applied Basic Research 21 Foundation(No.2021A1515010403).
文摘Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown to facilitate cancer progression by modulating oncogenic variants.However,its specific role and underlying mechanisms in hepatocellular carcinoma(HCC)remain to be elucidated.Methods:PTBP1 expression was evaluated in HCC tissues and cell lines.Subsequently,cells were transfected with vectors designed for PTBP1 overexpression or downregulation.The biological function of PTBP1 was assessed in vitro and in vivo using MTS assays,colony formation assays,transwell assays,xenograft formation,tail vein injection,and orthotopic models.Transcriptome analysis was conducted to elucidate the underlying molecular mechanisms.Results:Our findings demonstrated that PTBP1 exhibited elevated expression in HCC cell lines and tissues.Furthermore,its expression positively correlated with overall and disease-free survival rates,as well as tumor grade and stage.PTBP1 knockdown reduced HCC cell proliferation,migration,and invasion in vitro and suppressed hepatocarcinoma xenograft growth and infiltration in vivo.RNA sequencing(RNA-Seq)analysis identified the AS events associated with PTBP1.PTBP1 functionally enhanced cell proliferation,invasion,and migration by modulating the AS of the microtubule-associated protein tau(MAPT)gene and promoting oncogene expression.Notably,the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC.Conclusions:PTBP1-guided AS of the MAPT gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.
基金supported by grants from the Mega-Project for National Science and Technology Development under the"11th and 12th Five-Year Plan of China"(2013ZX10004901,2013ZX10004904and 2014ZX10004008)
文摘Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE.Data sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.Results: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.
基金supported by the National Natural Science Foundation of China (No. 42177392)the National Key Research and Development Program of China (No. 2019YFC1803601)the Fundamental Research Funds for the Central Universities of Central South University (No. 2021zzts0122)。
文摘Smelting activities pose serious environmental problems due to the local and regional heavy metal pollution in soils they cause. It is therefore important to understand the pollution situation and its source in the contaminated soils. In this paper, data on heavy metal pollution in soils resulting from Pb/Zn smelting(published in the last 10 years) in China was summarized. The heavy metal pollution was analyzed from a macroscopic point of view. The results indicated that Pb, Zn, As and Cd were common contaminants that were present in soils with extremely high concentrations. Because of the extreme carcinogenicity, genotoxicity and neurotoxicity that heavy metals pose, remediation of the soils contaminated by smelting is urgently required. The primary anthropogenic activities contributing to soil pollution in smelting areas and the progressive development of accurate source identification were performed. Due to the advantages of biominerals, the potential of biomineralization for heavy metal contaminated soils was introduced. Furthermore, the prospects of geochemical fraction analysis, combined source identification methods as well as several optimization methods for biomineralization are presented, to provide a reference for pollution investigation and remediation in smelting contaminated soils in the future.
文摘OBJECTIVE To study the effect of transforming growth factor β1 （TGF-β1） on differentiation of rhabdomyosarcoma （RMS） cells METHODS RD （human embryonal RMS cell line） cells, cultured in differentiation medium containing 9-cis retinoic acid （9CRA）, were treated with TGF-β1. Proliferation of the cells was examined by the MTT assay. The differentiation specific proteins （sarcomeric actin and MyHC） and myogenic transcription factors （MyoD1 and myogenin） in the RD cells were assessed by immunofluorescence staining. RESULTS Compared to control cells, treatment with lower concentrations of TGF-β1 （0.1 and 0.2 ng/ml） induced an increase in OD values after 4 d （P〈0.01）, whereas higher concentrations of TGF-β1 （2 and 5 ng/ml） led to a reduction of cell viability （P〈0.01）. After exposure to 9CRA, the viability of the cells decreased significantly （P〈0.01）, while sarcomeric actin, MyHC and myogenin were induced. These changes were antagonized by TGF-β1 （0.1 ng/ml）. No changes were observed in expression of MyoD1. CONCLUSION The RMS cells, derived from myogenic progenitors are committed to a myogenic fate, but are arrested in the differentiation course by the addition of TGF-β1 which represses some of the myogenic transcription factors.
基金financial support provided by the Xinjiang Uygur Autonomous Region Key R&D Project Task Special-Department and Department Linkage Project(No.2022B01051)Major Project of Regional Joint Foundation of China(No.U21A20107)+1 种基金Hunan Provincial Natural Science Foundation of China(No.2024JJ4021)the Xinjiang Uygur Autonomous Region Tianchi Introduction Plan(No.2024XGYTCYC03)。
文摘The load-bearing performance(LBP)of pumpable supports(PPS)is crucial for the stability of longwall pre-driven recovery room(PRR)surrounding rock.However,the unbalanced bearing coefficient(UBC)of the PPS(undertaking unequal load along the mining direction)has not been investigated.A mechanical model of the PRR was established,considering the main roof cantilever beam structure,to derive an assessment formula for the load,the failure criteria,and the UBC of the PPS.Subsequently,the generation mechanisms,and influencing factors of the UBC were revealed.Global sensitivity analysis shows that the main roof hanging length(l_(2))and the spacing between the PPS(r)significantly impact the UBC.A novel design of the PPS and the coupling control technology were proposed and applied to reduce the UBC of the PPS in the adjacent longwall PRR.Monitor results showed no failure of the PPS at the test site,with the UBC(ζ)reduced to 1.1 consistent with the design value(1.15)basically,fully utilizing the collaborative LBP of the PPS.Finally,the maximum roof-to-floor convergence of the PRR was 234 mm,effectively controlling the stability of the surrounding rock of the PRR and ensuring the mining equipment recovery.
基金the China Scholarship Council for the award of fellowship and funding No.201908510177 and No.202106050030funded by dtec.bw-Digitalization and Technology Research Center of the Bundeswehr which project DMF+1 种基金The AMABML project founded by the Zentrum für Hochleistungsmaterialien(ZHM)DEZAIN project for financial support via grant from GIF,the German-Israeli Foundation for Scientific Research and Development。
文摘The voltage drop appearing at Mg anode-electrolyte interface is a critical issue for the battery power and energy density of aqueous primary Mg-air batteries.The respective voltage loss is typically assigned to the deposits layer forming on the anode surface during discharge.In this work,we experimentally and computationally investigate the critical factors affecting the voltage drop at Mg anode towards a deeper understanding of the contribution of deposit and its growth.A two-dimensional(2D)mathematical model is proposed to compute the voltage drop of Mg-0.15Ca wt.%alloy(Mg-0.15Ca)by means of a semi-empirical formulas and experiments-based modification model,considering the effect of discharge current density,the negative difference effect(NDE)and surface deposits layer itself.This model is utilized to simulate the discharge potential of the anode at predefined experimental current densities.The computed voltage drop(half-cell voltage)is in good agreement with the experimental value.The applicability of the mathematical model is successfully validated on the second material(namely high-purity Mg).
基金supported by the National Natural Sci-ence Foundation of China(grant numbers:82002432,82370199)the National Key Research and Development of China(grant number:2020AAA0109504)the Natural Science Foundation of Shandong Province(grant number:ZR2020QH179).
文摘Objective:To evaluate whether improved progression-free survival(PFS)from radiotherapy(RT)translates into an overall survival(OS)benefit for diffuse large B-cell lymphoma(DLBCL).Methods:A systematic literature search identified randomized controlled trials(RCTs)and retrospective studies that compared combined-modality therapy(CMT)with chemotherapy(CT)alone.Weighted regression analyses were used to estimate the correlation between OS and PFS benefits.Cohen’s kappa statistic assessed the consis-tency between DLBCL risk-models and PFS patterns.Furthermore,the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio(HR)according to the PFS patterns.Results:For both 7 RCTs and 52 retrospective studies,correlations were found between PFS HR(HRPFS)and OS HR(HROS)at trial level(r=0.639-0.876),and between PFS and OS rates at treatment-arm level,regardless of CT regimens(r=0.882-0.964).Incorporating RT into CT increased about 18%of PFS,and revealed a different OS benefit profile.Patients were stratified into four CT-generated PFS patterns(>80%,>60-80%,>40-60%,and≤40%),which was consistent with risk-stratified subgroups(kappa>0.6).Absolute gain in OS from RT ranged from≤5%at PFS>80%to about 21%at PFS≤40%,with pooled HROS from 0.70(95%CI,0.51-0.97)to 0.48(95%CI,0.36-0.63)after rituximab-based CT.The OS benefit of RT was predominant in intermediate-and high-risk patients with PFS≤80%.Conclusion:We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.
基金financial support from the National Natural Science Foundation of China(Nos.51804111,51974117,51904102,and 52074117)Natural Science Foundation of Hunan Province(No.2020JJ5194)the Postgraduate Scientific Research Innovation Project of Hunan Province(No.CX20200991)。
文摘In multi-seam mining,the interlayer rock strata between the upper coal seam(UCS)and the lower coal seam(LCS)appear damage and strength weakening after mining the UCS.Ground stability control of the gob-side entry retaining(GER)under the gob with close distance coal seams(CDCS)is faced with difficulties due to little attention to GER under this condition.This paper focuses on surrounding rock stability control and technical parameters design for GER under the gob with CDCS.The floor rock strata damage characteristics after mining the UCS is first evaluated and the damage factor of the interlayer rock strata below the UCS is also determined.Then,a structural mechanics model of GER surrounding rock is set up to obtain the main design parameters of the side-roadway backfill body(SBB)including the maximum and minimum SBB width calculation formula.The optimal SBB width and the water-to-cement ratio of high water quick-setting material(HWQM)to construct the SBB are determined as 1.2 m and 1.5:1.0,respectively.Finally,engineering trial tests of GER are successfully carried out at#5210 track transportation roadway of Xingwu Colliery.Research results can guide GER design under similar mining and geological conditions.
基金supported by the National Key Research and Development Program,China(No.2019YFC1803601)the Fundamental Research Funds for the Central Universities of Central South University(No.2021zzts0121)the Hunan Provincial Innovation Foundation for Postgraduate(No.CX20210203).
文摘Smelting activities are the main pathway for the anthropogenic release of heavy metals(HMs)into the soil-groundwater environment.It is vital to identify the factors affecting HMs pollution to better prevent and manage soil pollution.The present study conducted a comprehensive investigation of HMs in soil from a large abandoned Zn smelting site.An integrated approach was proposed to classify and quantify the factors affecting HMs pollution in the site.Besides,the quantitative relationship between hydrogeological characteristics,pollution transmission pathways,smelting activities and HMs pollutionwas established.Results showed that the soils were highly contaminated by HMs with a pollution index trend of As>Zn>Cd>Pb>Hg.In identifying the pollution hotspots,we conclude that the pollution hotspots of Pb,As,Cd,and Hg present a concentrated distribution pattern.Geo-detector method results showed that the dominant driving factors for HMs distribution and accumulation were the potential pollution source and soil permeability.Additionally,the main drivers are variable for different HMs,and the interaction among factors also enhanced soil HMs contamination.Our analysis illustrates how the confounding influences from complex environmental factors can be distilled to identify key factors in pollution formation to guide future remediation strategies.
基金China Scholarship Council for the award of fellowship and funding(201604910527)。
文摘The corrosion performances of the as-cast and solution-treated Mg-0.5Zn samples were investigated in 0.9%Na Cl solution and compared.From the electrochemical measurement results and corrosion morphology observations,it is found that the corrosion resistance of Mg-0.5Zn deteriorated with the extension of solution treatment duration.The main reason was the formation of Fe-Si precipitates with higher Fe concentrations during heat treatment.The Fe-Si precipitates,especially the ones with high Fe contents influenced the corrosion initiation and propagation significantly.In regard of corrosion performance,the solution-treated and then extruded sample was also performing not as good as the cast and then directly extruded sample.
基金Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgements We thank Dr Jiang Zhu （Shanghai institute of hematology, Rui Jin hospital） and Dr Nelly Kieffer （CNRS LIA, Rui Jin hospital） for their comments. This work was supported by grants from the National High Tech Program of China （863, 2006AA02Z150）, the National Science Foundation of China （30525006）, the Science and Technology Commission of Shanghai Municipality （07XD14022, 06PJ14068）, ATIP program and BNP PARIBAS.
文摘The Small ubiquitin-related modifier （SUMO） conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investigate in vivo biological function of SUMO paralogs, we inactivated them in the early development of zebrafish. While zebrafish embryos deficient for all three SUMO paralogs, as Ubc9-deficient ones, displayed severe defects, loss of individual SUMO paralog was compatible with a normal development. SUMO-deficient embryos can be rescued by a single human or zebrafish SUMO. While key structural basic lysine residues and N-terminal unstructured stretch of SUMO are critical for in vivo rescue, the consensus Kll sumoylation site of SUMO2 is dispensable, implying that chain formation on this potential site is unessential for normal development. Inactivation of all three SUMOs triggered p53- dependent apoptosis and further inactivation of p53 restored normal zebrafish development. Interestingly, we also demonstrate that the dominant negative truncated form of p53, Δ113p53, significantly blunts SUMO depletion-induced p53 activity in vivo. Taken together, our results suggest that SUMO paralogs are indispensable, but redundant, in the early development of zebrafish.
