AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced...AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 (MBD1) on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 (SIRT3) expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.展开更多
Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of...Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.展开更多
The optimization of fermentation medium is important for synthetic biological secondary metabolite productions.The effect of rotation speed,inoculum amount,and medium supplements on the cell growth and Lycogen^TM secr...The optimization of fermentation medium is important for synthetic biological secondary metabolite productions.The effect of rotation speed,inoculum amount,and medium supplements on the cell growth and Lycogen^TM secretion of photobacterium Rhodobacter sphaeroides WL-APD911 was evaluated.The results reveal that a higher rotational speed exhibit a higher cell density,and the increasing in the amount of inoculum amount show a slight augment on the growth of R.sphaeroides WL-APD911.In the case of nitrogen sources adding,Lycogen^TM production was achieved with a 0.5 mM l-lysine supplementation.Moreover,the attention of Tween 80 presented a tremendous increase in the secondary metabolite.Response surface methodology(RSM)exhibited the optimization of medium supplements for Lycogen^TM invention is accomplished at molasses concentration of 10 g/L,yeast extract concentration of 40 g/L,0.3%Tween 80 and NaCl concentration of 5 g/L,respectively.Further,the batch fermentation is carried out in both 5 L and 20 L fermentors to study the scale-up process factors to be adopted.At a 20 L fermentor,Lycogen^TM yields under the optimal culture condition are over 2 times than in the shake flask.The present results provide the Lycogen^TM optimal culture mediums,scale-up procedures and efficient extractions from R.sphaeroides WL-APD911.展开更多
Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients,and genetic defects have been recognized as the main cause of acephalic spermatozoa syn...Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients,and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome.Spermatogenesis and centrioleassociated 1 like(SPATC1L)is indispensable for maintaining the integrity of sperm head-to-tail connections in mice,but its roles in human sperm and early embryonic development remain largely unknown.Herein,we conducted whole-exome sequencing(WES)of 22 infertile men with acephalic spermatozoa syndrome.An in silico analysis of the candidate variants was conducted,and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility.We identified biallelic mutations in SPATC1L(c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X)from a patient whose sperm displayed complete acephalia.Both SPATC1L variants are rare and deleterious.SPATC1L is mainly expressed at the head–tail junction of elongating spermatids.Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro.Moreover,none of the patient’s four attempts at intracytoplasmic sperm injection(ICSI)resulted in a transplantable embryo,which suggests that SPATC1L defects might affect early embryonic development.In conclusion,this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome.Furthermore,WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.展开更多
To investigate whether alcohol and tea con-sumption has an etiological association with nasophar-yngeal carcinoma(NPC)in a high-incident population,a large scale case-control study was conducted.The study included 284...To investigate whether alcohol and tea con-sumption has an etiological association with nasophar-yngeal carcinoma(NPC)in a high-incident population,a large scale case-control study was conducted.The study included 2846 individuals in Guangdong Province,China,with 1387 newly diagnosed cases of NPC and 1459 frequency-matched controls.Exposure histories of alcohol and tea consumption were obtained via personal inter-views.Information regarding socio-demographic charac-teristics(age,sex,education,dialect and household type),family history of NPC,Epstein-Barr virus(EBV)infection,dietary habits and other potential confounding factors was also studied.An analysis was performed using uncondi-tional logistic regression to calculate odds ratios(OR)and 95%confidence intervals(CI).The risk of NPC was found to be associated with habitual alcohol consumption and tea consumption.Tea consumption has been associated with a decreased occurrence of NPC(OR=0.62),while con-sumption of alcohol was associated with a complex effect.Specifically,moderate consumption of alcohol was associated with decreased risk of NPC,while overuse,especially strong distillate spirits,appeared to be a risk factor.展开更多
The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins.However,the underlying molecular mechanism remain...The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins.However,the underlying molecular mechanism remains largely unknown.Here,we report that Src homology domain tyrosine phosphatase 2(Shp2;encoded by the protein tyrosine phosphatase,nonreceptor type 11[Ptpn11]gene)is abundant in spermatogonia but markedly decreases in meiotic spermatocytes.Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8(Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process.Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die;moreover,the surviving spermatocytes reached the leptotene stage early at postnatal day 9(PN9)and the pachytene stage at PN11-13.In preleptotene spermatocytes,Shp2 deletion disrupted the expression of meiotic genes,such as disrupted meiotic cDNA 1(Dmc1),DNA repair recombinase rad51(Rad51),and structural maintenance of chromosome 3(Smc3),and these deficiencies interrupted spermatocyte meiosis.In GC-1 cells cultured in vitro,Shp2 knockdown suppressed the retinoic acid(RA)-induced phosphorylation of extracellular-regulated protein kinase(Erk)and protein kinase B(Akt/PKB)and the expression of target genes such as synaptonemal complex protein 3(Sycp3)and Dmc1.Together,these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription,thus providing a potential treatment target for male infertility.展开更多
基金primarily financially supported by the National Natural Science Foundation of China(No.51871245)the National Key R&D Program of China(No.2017YFE0301505)State Key Laboratory for Powder Metallurgy as well as State Key Laboratory of Light Weight and High Strength Structural Materials,Central South University,China。
基金the National Science Fund for Distinguished Young Scholars of China,No.81625016the National Science Foundation of China,No.81502031 and No.81772555+1 种基金Shanghai Municipal Commission of Health and Family Planning Grant,No.20154Y0090Youth Research Foundation of Shanghai Municipal Commission of Health and Family Planning,No.Z0124Y074
文摘AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 (ZEB1) was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 (MBD1) on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 (SIRT3) expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.
基金Supported by Basic Scientific Research Business of Chinese Academy of Medical Sciences,No.2016ZX310020
文摘Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.
基金This work was supported by grants from the Ministry of Science and Technology,Taiwan,ROC(MOST 104-2221-E-005-096-MY2,and MOST 104-2628-E-005-004-MY3).We thank the projects of Center for Stem Cell Research,Kaohsiung Medical University,Kaohsiung,Taiwan,KMU-TP104G00 and KMU-TP104G02-05.The financial supports were also from KMU-DK105005 and NSYSUKMU105-P 007.
文摘The optimization of fermentation medium is important for synthetic biological secondary metabolite productions.The effect of rotation speed,inoculum amount,and medium supplements on the cell growth and Lycogen^TM secretion of photobacterium Rhodobacter sphaeroides WL-APD911 was evaluated.The results reveal that a higher rotational speed exhibit a higher cell density,and the increasing in the amount of inoculum amount show a slight augment on the growth of R.sphaeroides WL-APD911.In the case of nitrogen sources adding,Lycogen^TM production was achieved with a 0.5 mM l-lysine supplementation.Moreover,the attention of Tween 80 presented a tremendous increase in the secondary metabolite.Response surface methodology(RSM)exhibited the optimization of medium supplements for Lycogen^TM invention is accomplished at molasses concentration of 10 g/L,yeast extract concentration of 40 g/L,0.3%Tween 80 and NaCl concentration of 5 g/L,respectively.Further,the batch fermentation is carried out in both 5 L and 20 L fermentors to study the scale-up process factors to be adopted.At a 20 L fermentor,Lycogen^TM yields under the optimal culture condition are over 2 times than in the shake flask.The present results provide the Lycogen^TM optimal culture mediums,scale-up procedures and efficient extractions from R.sphaeroides WL-APD911.
基金This study was supported by the National Natural Science Foundation of China(No.82001616)the Natural Science Foundation of Fujian Province of China(No.2019J01565 and 2017J01361)the Medical and Health Guidance Project of Xiamen(No.3502Z20209004).
文摘Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients,and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome.Spermatogenesis and centrioleassociated 1 like(SPATC1L)is indispensable for maintaining the integrity of sperm head-to-tail connections in mice,but its roles in human sperm and early embryonic development remain largely unknown.Herein,we conducted whole-exome sequencing(WES)of 22 infertile men with acephalic spermatozoa syndrome.An in silico analysis of the candidate variants was conducted,and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility.We identified biallelic mutations in SPATC1L(c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X)from a patient whose sperm displayed complete acephalia.Both SPATC1L variants are rare and deleterious.SPATC1L is mainly expressed at the head–tail junction of elongating spermatids.Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro.Moreover,none of the patient’s four attempts at intracytoplasmic sperm injection(ICSI)resulted in a transplantable embryo,which suggests that SPATC1L defects might affect early embryonic development.In conclusion,this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome.Furthermore,WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
基金supported by the National Natural Science Foundation of China(Grant Nos.30671798 and 30471487)the National Science and Technology Support Program of China(No.2006BAI02A11)the National Major Basic Research Program of China(863 Program)(No.2006AA02A404).
文摘To investigate whether alcohol and tea con-sumption has an etiological association with nasophar-yngeal carcinoma(NPC)in a high-incident population,a large scale case-control study was conducted.The study included 2846 individuals in Guangdong Province,China,with 1387 newly diagnosed cases of NPC and 1459 frequency-matched controls.Exposure histories of alcohol and tea consumption were obtained via personal inter-views.Information regarding socio-demographic charac-teristics(age,sex,education,dialect and household type),family history of NPC,Epstein-Barr virus(EBV)infection,dietary habits and other potential confounding factors was also studied.An analysis was performed using uncondi-tional logistic regression to calculate odds ratios(OR)and 95%confidence intervals(CI).The risk of NPC was found to be associated with habitual alcohol consumption and tea consumption.Tea consumption has been associated with a decreased occurrence of NPC(OR=0.62),while con-sumption of alcohol was associated with a complex effect.Specifically,moderate consumption of alcohol was associated with decreased risk of NPC,while overuse,especially strong distillate spirits,appeared to be a risk factor.
基金This work was supported by the National Key R&D Program of China(No.2018YFC1003701 and No.2017YFC1001402)the National Natural Science Foundation of China(Grant No.31171375).
文摘The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins.However,the underlying molecular mechanism remains largely unknown.Here,we report that Src homology domain tyrosine phosphatase 2(Shp2;encoded by the protein tyrosine phosphatase,nonreceptor type 11[Ptpn11]gene)is abundant in spermatogonia but markedly decreases in meiotic spermatocytes.Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8(Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process.Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die;moreover,the surviving spermatocytes reached the leptotene stage early at postnatal day 9(PN9)and the pachytene stage at PN11-13.In preleptotene spermatocytes,Shp2 deletion disrupted the expression of meiotic genes,such as disrupted meiotic cDNA 1(Dmc1),DNA repair recombinase rad51(Rad51),and structural maintenance of chromosome 3(Smc3),and these deficiencies interrupted spermatocyte meiosis.In GC-1 cells cultured in vitro,Shp2 knockdown suppressed the retinoic acid(RA)-induced phosphorylation of extracellular-regulated protein kinase(Erk)and protein kinase B(Akt/PKB)and the expression of target genes such as synaptonemal complex protein 3(Sycp3)and Dmc1.Together,these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription,thus providing a potential treatment target for male infertility.