At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut m...At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.展开更多
Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmac...Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.展开更多
Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challen...Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.展开更多
Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomi...Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! （i.e.,Ile350Thr： rs12450550T 〉 C and Glu69Asp： rs3760413T 〉 G） and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes （Thr/lle ＋ Thr/Thr） conferred a 1.47-fold increased risk of breast cancer （OR=1.47, 95% CI=I. 13-1.92）. The variant Ile350Thr was also associated with early onset of breast cancer （r = -0.116, P = 0.002）. The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that （49.4 years） for Ile/Ile genotype carriers （P = 0.006）. Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.展开更多
Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients（Chaffer and Weinberg,2011）.Different primary cancers have distinct spreading routes via the blood or ...Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients（Chaffer and Weinberg,2011）.Different primary cancers have distinct spreading routes via the blood or the lymphatics or through both routes,which presents challenge for effective cancer treatment（Qian et aL,2017）.展开更多
The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warra...The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biom展开更多
BACKGROUND： Recent studies have paid much attention to the newly found neuregulin-1, which might be closely linked to the molecular genetics of schizophrenia. OBJECTIVE： To investigate the association of neuregulin-...BACKGROUND： Recent studies have paid much attention to the newly found neuregulin-1, which might be closely linked to the molecular genetics of schizophrenia. OBJECTIVE： To investigate the association of neuregulin-related genes with schizophrenia, and to summarize the advancements in this current research. RETRIEVAL STRATEGY： Using the terms ＂neuregulins, gene, schizophrenia＂, we retrieved articles published from January 2000 to June 2007 from http：//www.ncbi.nlm.gov, http：//www.elsevier.lib.tsinghua.edu.cn, and http：//www.cjfd.cnki.net to identify studies addressing the association of neuregulin-related genes to schizophrenia. At the same time, we searched more than 10 medical journals by hand. The languages were limited to English and Chinese. Forty-two manuscripts were obtained and were firstly screened. Inclusion criteria： studies on neuregulins, schizophrenia, neuregulin-1, and the pathogenesis of schizophrenia, including randomized, blinded, and other original studies. Exclusion criteria： studies not related to schizophrenia, or repetitive studies. LITERATURE EVALUATION： The included 42 manuscripts were sorted. Twenty-one were selected as references for this article： fourteen were basic studies, and the remaining articles were case-controlled studies or other. DATA SYNTHESIS： Neuregulins are primarily expressed in the nervous system and heart, and limited expression is also seen in other tissues.. These proteins transmit signals among certain cells and play an important role in normal development of the nervous system. Neuregulin-1 is a typical neuregulin-related gene. Neuregulin genes are closely related to glutamatergic, GABAergic, and dopaminergic neurons. CONCLUSION： Neuregulin-related genes, such as neuregulin-1, are important and promising candidate genes for studying schizophrenia disease. Their roles in the onset of schizophrenia, neuregulin-related gene expression products, and correlations of ErbB receptor to schizophrenia symptoms need to be further investigated. Furt展开更多
Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathoge...Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML.However,the functional heterogeneity including the drug response of coexistent LICs remains unclear.Therefore,this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.Methods:Spleen cells from the primary Setd2^(-/-)-AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model.Flow cytometry was used to analyze the immunophenotype of the leukemic mice.Whole-genome sequencing was conducted to detect secondary hits responsible for leukemia transformation.A serial transplantation assay was used to determine the self-renewal potential of Setd2^(-/-)-AML cells.A limiting-dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells.Bulk and single-cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs.Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs.Results:In this study,we observed an aged Setd2^(-/-)mouse developing AML with co-mutation of Nras^(G12S) and Braf^(K520E).Further investigation identified two types of LICs residing in the c-Kit^(+)B220^(+)Mac-1^(-)and c-Kit^(+)B220^(+)Mac-1^(+)subsets,respectively.In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs.Besides,an intrinsic doxorubicinresistant transcriptional signature was uncovered in c-Kit^(+)B220^(+)Mac-1^(+)cells.Indeed,doxorubicin plus cytarabine(DA),the standard chemotherapeutic regimen used in AML treatment,could specifically kill c-Kit^(+)B220^(+)Mac-1^(−)cells,but it hardly affected c-Kit^(+)B220^(+)Mac-1^(+)cells.Transcriptome analysis unveil展开更多
菌草(JUNCAO)是用于栽培食用菌、药用菌的草本植物。以菌草绿洲一号为研究材料,通过植物组织表面消毒、研磨组织、培养基培养等方法分离纯化内生菌,并进一步通过分子手段鉴定菌株,通过平板对峙法等方法对其生物学特性进行研究。16S r DN...菌草(JUNCAO)是用于栽培食用菌、药用菌的草本植物。以菌草绿洲一号为研究材料,通过植物组织表面消毒、研磨组织、培养基培养等方法分离纯化内生菌,并进一步通过分子手段鉴定菌株,通过平板对峙法等方法对其生物学特性进行研究。16S r DNA序列同源性分析结果表明,该菌株为Enterobacter ludwigii;平板对峙等生物学特性试验结果表明,该菌株对马铃薯早疫病菌具有拮抗作用。该菌株具有溶磷性、接触酶反应呈阳性、能使明胶液化、水解淀粉等生物学特性。根据菌株的拮抗特性和其他生物学特性结果可以推测,该菌株可作为生防菌防治植物病原菌及作为促生菌促进植物的生长,提高产量。展开更多
为研究蛋白的共价接枝改性对其乳化稳定性的影响,本文以乳清分离蛋白(whey protein isolate,WPI)和表没食子儿茶素没食子酸酯(epigallocatechingallate,EGCG)为原料,通过自由基接枝法制备WPI-EGCG复合物。利用扫描电镜(SEM)对其微观结...为研究蛋白的共价接枝改性对其乳化稳定性的影响,本文以乳清分离蛋白(whey protein isolate,WPI)和表没食子儿茶素没食子酸酯(epigallocatechingallate,EGCG)为原料,通过自由基接枝法制备WPI-EGCG复合物。利用扫描电镜(SEM)对其微观结构进行观测,通过测定界面蛋白吸附量、界面流变学特性来探究共价接枝对界面特性的影响;进而以WPI-EGCG接枝物为乳化剂构建番茄红素纳米乳液,并对其物理化学稳定性及储藏稳定性进行研究。结果表明,EGCG的自由基接枝改变了WPI的结构,使之具有更高的黏度和界面稳定性,使以接枝物为乳化剂的番茄红素纳米乳液体系具有更高的物化稳定性。WPI-EGCGE接枝物稳定的番茄红素纳米乳液在37℃下储藏30 d后粒径和ζ-电位绝对值分别增加了268.3 nm和17.6 mV,乳液中番茄红素的保留率仍有66.23%,呈现出更佳的番茄红素保护效果。本研究为功能活性物质纳米乳液载运体系的构建提供了参考。展开更多
基金supported by the National Key R&D Program of China(No.2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(CIFMS+2 种基金Nos.2022-I2M-JB-011,2022-I2M-2-002,and 2021-I2M-1-007,China)National Natural Science Foundation of China(Nos.82173888 and 81973290)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062,China)。
文摘At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.
基金supported by the National Key R&D Program of China(Grant No.:2022YFA0806400)the CAMS Innovation Fund for Medical Sciences(Grant Nos.:2022-I2M-1-028,2022-I2M-2-002,and 2021-I2M-1-007)+1 种基金the National Natural Science Foundation of China(Grant Nos.:81973290 and 82173888)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study,China(Grant No.:Z141102004414062)。
文摘Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
基金supported by the National Natural Science Foundation of China(No.82073628,81871876 and 82173609).
文摘Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.
基金supported by the National Natural Science Foundation of China (grants 30671813,30872178,81072366,and 81273149)Guangdong Provincial High Level Experts Grants (No.2010-79)+1 种基金Changjiang Scholars and Innovative Research Team in University grant (No.IRT0961)Guangdong Natural Science Foundation Team Grant (No.10351012003000000 to Dr.J.Lu)
文摘Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! （i.e.,Ile350Thr： rs12450550T 〉 C and Glu69Asp： rs3760413T 〉 G） and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes （Thr/lle ＋ Thr/Thr） conferred a 1.47-fold increased risk of breast cancer （OR=1.47, 95% CI=I. 13-1.92）. The variant Ile350Thr was also associated with early onset of breast cancer （r = -0.116, P = 0.002）. The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that （49.4 years） for Ile/Ile genotype carriers （P = 0.006）. Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.
基金supported by the National Natural Science Foundation of China(Nos.31171270 and 31671375)the research start-up fellowship of University of the Sunshine Coast to M.Z
文摘Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients（Chaffer and Weinberg,2011）.Different primary cancers have distinct spreading routes via the blood or the lymphatics or through both routes,which presents challenge for effective cancer treatment（Qian et aL,2017）.
基金supported by the National Natural Science Foundation of China Grants 81872127,81602289(FQ)81872694,81673267,81473040(JL)+3 种基金81402753,81672303,81871876(LY)Guangzhou Science Research Program General Project Grant 201707010123(FQ)Guangzhou Municipal Scientific Research Project Grant 1201630073(FQ)Guangdong High School Young Innovative Talents Project Grant 2015KQNCX136(FQ).
文摘The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biom
文摘BACKGROUND： Recent studies have paid much attention to the newly found neuregulin-1, which might be closely linked to the molecular genetics of schizophrenia. OBJECTIVE： To investigate the association of neuregulin-related genes with schizophrenia, and to summarize the advancements in this current research. RETRIEVAL STRATEGY： Using the terms ＂neuregulins, gene, schizophrenia＂, we retrieved articles published from January 2000 to June 2007 from http：//www.ncbi.nlm.gov, http：//www.elsevier.lib.tsinghua.edu.cn, and http：//www.cjfd.cnki.net to identify studies addressing the association of neuregulin-related genes to schizophrenia. At the same time, we searched more than 10 medical journals by hand. The languages were limited to English and Chinese. Forty-two manuscripts were obtained and were firstly screened. Inclusion criteria： studies on neuregulins, schizophrenia, neuregulin-1, and the pathogenesis of schizophrenia, including randomized, blinded, and other original studies. Exclusion criteria： studies not related to schizophrenia, or repetitive studies. LITERATURE EVALUATION： The included 42 manuscripts were sorted. Twenty-one were selected as references for this article： fourteen were basic studies, and the remaining articles were case-controlled studies or other. DATA SYNTHESIS： Neuregulins are primarily expressed in the nervous system and heart, and limited expression is also seen in other tissues.. These proteins transmit signals among certain cells and play an important role in normal development of the nervous system. Neuregulin-1 is a typical neuregulin-related gene. Neuregulin genes are closely related to glutamatergic, GABAergic, and dopaminergic neurons. CONCLUSION： Neuregulin-related genes, such as neuregulin-1, are important and promising candidate genes for studying schizophrenia disease. Their roles in the onset of schizophrenia, neuregulin-related gene expression products, and correlations of ErbB receptor to schizophrenia symptoms need to be further investigated. Furt
基金National Natural Science Foundation of China,Grant/Award Numbers:81670149,81870102Samuel Waxman Cancer Research FoundationFoundation of Key Laboratory of Veterinary Biotechnology,Grant/Award Number:shklab202008。
文摘Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML.However,the functional heterogeneity including the drug response of coexistent LICs remains unclear.Therefore,this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.Methods:Spleen cells from the primary Setd2^(-/-)-AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model.Flow cytometry was used to analyze the immunophenotype of the leukemic mice.Whole-genome sequencing was conducted to detect secondary hits responsible for leukemia transformation.A serial transplantation assay was used to determine the self-renewal potential of Setd2^(-/-)-AML cells.A limiting-dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells.Bulk and single-cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs.Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs.Results:In this study,we observed an aged Setd2^(-/-)mouse developing AML with co-mutation of Nras^(G12S) and Braf^(K520E).Further investigation identified two types of LICs residing in the c-Kit^(+)B220^(+)Mac-1^(-)and c-Kit^(+)B220^(+)Mac-1^(+)subsets,respectively.In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs.Besides,an intrinsic doxorubicinresistant transcriptional signature was uncovered in c-Kit^(+)B220^(+)Mac-1^(+)cells.Indeed,doxorubicin plus cytarabine(DA),the standard chemotherapeutic regimen used in AML treatment,could specifically kill c-Kit^(+)B220^(+)Mac-1^(−)cells,but it hardly affected c-Kit^(+)B220^(+)Mac-1^(+)cells.Transcriptome analysis unveil
文摘菌草(JUNCAO)是用于栽培食用菌、药用菌的草本植物。以菌草绿洲一号为研究材料,通过植物组织表面消毒、研磨组织、培养基培养等方法分离纯化内生菌,并进一步通过分子手段鉴定菌株,通过平板对峙法等方法对其生物学特性进行研究。16S r DNA序列同源性分析结果表明,该菌株为Enterobacter ludwigii;平板对峙等生物学特性试验结果表明,该菌株对马铃薯早疫病菌具有拮抗作用。该菌株具有溶磷性、接触酶反应呈阳性、能使明胶液化、水解淀粉等生物学特性。根据菌株的拮抗特性和其他生物学特性结果可以推测,该菌株可作为生防菌防治植物病原菌及作为促生菌促进植物的生长,提高产量。
