Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line se...Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.展开更多
C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed ...C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family;nonetheless,biological functions of protein C-mannosylation are not yet fully understood,especially in tumor progression.Vasculogenic mimicry(VM)is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells,enabling the tumors to form matrix-embedded vasculogenic structures,containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors.In this study,we focused on DPY19L3,a C-mannosyltransferase,and aimed to unravel its role in VM.Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells.Re-expression of wild-type DPY19L3 recovered VM formation;however,DPY19L3 isoform2,an enzymatic activity-defect mutant,did not restore it,suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function.Furthermore,the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability.Altogether,our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis.展开更多
Sustainable rice production in Sierra Leone faces serious constraints due to soil acidity, low cation exchange capacity, low nutrient contents accelerated mineralization of soil organic matter and soil loss by erosion...Sustainable rice production in Sierra Leone faces serious constraints due to soil acidity, low cation exchange capacity, low nutrient contents accelerated mineralization of soil organic matter and soil loss by erosion (particularly on the uplands). One possible approach to addressing the soil constraints to rice production both on uplands and lowlands of Sierra Leone is the recycling of rice residues through biochar production and application to soils. A pot experiment was conducted to investigate the effects of application of biochar from rice residues on (i) soil physicochemical properties and (ii) the early growth characteristics of two rice varieties, NERICA L19 and ROK3. The experiment was arranged in a completely randomized design (CRD) with two biochar levels (0 and 15 g/kg soil) and two rice varieties in three replications. For the biochar treated soils (+biochar), 75 g rice straw biochar was applied to 5 kg air-dry soil (15 kg biochar/kg soil), mixed thoroughly and placed into perforated black polythene bags. Seeds of two rice varieties, NERICA L19 and ROK3 were planted on the treated and untreated soils for eight weeks. Application of biochar improved available phosphorus, exchangeable cations and cation exchange capacity in biochar treated soils compared to the control soil without biochar. Plant height, tiller number, and dry biomass weight of both rice varieties grown in soils amended with rice straw biochar were significantly higher than those on untreated soils. The most remarkable increase in plant growth characteristics as a result of biochar addition to soil was reflected in the biomass yield and tiller numbers. Dry shoot biomass for ROK3 rice variety varied significantly from a mean of 3.5 g (control) to 26.2 g (+biochar) while tiller numbers significantly varied from 10 (control) to 29.6 (+biochar). Similarly, for NERICA L19 rice variety, dry shoot biomass increased significantly from 4.5 g (control) to 22.7 g (+biochar) while tiller numbers increased significantly from a mean of 12.3 (control) to 30 (+biochar). Thus converting rice residues to biochar and applying to soil holds promise for improving rice production in Sierra Leone.展开更多
Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related...Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.展开更多
Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting...Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation （79%）, corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied （n = 5）, corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKCmutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKCand DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.展开更多
目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质...目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质瘤细胞中CWF19L1蛋白质的基础表达量,构建敲低慢病毒转染胶质瘤细胞,下调胶质瘤细胞中CWF19L1蛋白质表达。使用该稳转细胞系进行细胞周期、细胞增殖、细胞迁移和Transwell实验,以验证CWF19L1敲低对胶质瘤细胞功能的影响。结果生物信息分析表明肿瘤细胞中CWF19L1基因表达上调,蛋白质印迹法(WB)证明在U251胶质瘤细胞系中CWF19L1蛋白质表达量最高。敲低U251胶质瘤细胞中CWF19L1表达后,细胞周期实验示处于S/G2期的细胞比例上调(42.22%比33.00%P<0.05),CCK-8实验结果表明细胞数量明显上调(P<0.001),划痕实验显示划痕宽度明显缩短(P<0.001),迁移和侵袭实验证明穿过小室的细胞数量明显增多(P<0.001)。结论CWF19L1能够通过抑制细胞周期G1/S期转化,对胶质瘤细胞的增殖、迁移与侵袭能力产生抑制。展开更多
Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers...Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture atTaichong （LR3） andTaixi （KI3） using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture atTaichong andTaixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic res-onance imaging, which revealed that the amplitude of low-frequency lfuctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus （Brodmann area 18/19）, inferior occipital gyrus （Brodmann area 18） and cuneus （Brodmann area 18）, but decreased mainly in the gyrus rectus of the frontal lobe （Brodmann area 11）, inferi-or frontal gyrus （Brodmann area 44） and the center of the posterior lobe of the cerebellum. The present ifndings indicate that acupuncture atTaichong andTaixi speciifcally promote blood lfow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.展开更多
文摘Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.
文摘C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum.In humans,biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family;nonetheless,biological functions of protein C-mannosylation are not yet fully understood,especially in tumor progression.Vasculogenic mimicry(VM)is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells,enabling the tumors to form matrix-embedded vasculogenic structures,containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors.In this study,we focused on DPY19L3,a C-mannosyltransferase,and aimed to unravel its role in VM.Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells.Re-expression of wild-type DPY19L3 recovered VM formation;however,DPY19L3 isoform2,an enzymatic activity-defect mutant,did not restore it,suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function.Furthermore,the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability.Altogether,our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis.
文摘Sustainable rice production in Sierra Leone faces serious constraints due to soil acidity, low cation exchange capacity, low nutrient contents accelerated mineralization of soil organic matter and soil loss by erosion (particularly on the uplands). One possible approach to addressing the soil constraints to rice production both on uplands and lowlands of Sierra Leone is the recycling of rice residues through biochar production and application to soils. A pot experiment was conducted to investigate the effects of application of biochar from rice residues on (i) soil physicochemical properties and (ii) the early growth characteristics of two rice varieties, NERICA L19 and ROK3. The experiment was arranged in a completely randomized design (CRD) with two biochar levels (0 and 15 g/kg soil) and two rice varieties in three replications. For the biochar treated soils (+biochar), 75 g rice straw biochar was applied to 5 kg air-dry soil (15 kg biochar/kg soil), mixed thoroughly and placed into perforated black polythene bags. Seeds of two rice varieties, NERICA L19 and ROK3 were planted on the treated and untreated soils for eight weeks. Application of biochar improved available phosphorus, exchangeable cations and cation exchange capacity in biochar treated soils compared to the control soil without biochar. Plant height, tiller number, and dry biomass weight of both rice varieties grown in soils amended with rice straw biochar were significantly higher than those on untreated soils. The most remarkable increase in plant growth characteristics as a result of biochar addition to soil was reflected in the biomass yield and tiller numbers. Dry shoot biomass for ROK3 rice variety varied significantly from a mean of 3.5 g (control) to 26.2 g (+biochar) while tiller numbers significantly varied from 10 (control) to 29.6 (+biochar). Similarly, for NERICA L19 rice variety, dry shoot biomass increased significantly from 4.5 g (control) to 22.7 g (+biochar) while tiller numbers increased significantly from a mean of 12.3 (control) to 30 (+biochar). Thus converting rice residues to biochar and applying to soil holds promise for improving rice production in Sierra Leone.
文摘Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
文摘Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C （AURKCj and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation （79%）, corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied （n = 5）, corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKCmutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKCand DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.
文摘目的下调胶质瘤细胞系中CWF19L1(CWF19 like cell cycle control factor 1)的表达,探究胶质瘤细胞的增殖能力、迁移能力及侵袭能力的变化,为胶质瘤治疗研发新的治疗靶点。方法生物信息学分析肿瘤与正常组织中CWF19L1表达差异,验证胶质瘤细胞中CWF19L1蛋白质的基础表达量,构建敲低慢病毒转染胶质瘤细胞,下调胶质瘤细胞中CWF19L1蛋白质表达。使用该稳转细胞系进行细胞周期、细胞增殖、细胞迁移和Transwell实验,以验证CWF19L1敲低对胶质瘤细胞功能的影响。结果生物信息分析表明肿瘤细胞中CWF19L1基因表达上调,蛋白质印迹法(WB)证明在U251胶质瘤细胞系中CWF19L1蛋白质表达量最高。敲低U251胶质瘤细胞中CWF19L1表达后,细胞周期实验示处于S/G2期的细胞比例上调(42.22%比33.00%P<0.05),CCK-8实验结果表明细胞数量明显上调(P<0.001),划痕实验显示划痕宽度明显缩短(P<0.001),迁移和侵袭实验证明穿过小室的细胞数量明显增多(P<0.001)。结论CWF19L1能够通过抑制细胞周期G1/S期转化,对胶质瘤细胞的增殖、迁移与侵袭能力产生抑制。
基金supported by a grant from the National Key Basic Research and Development Project(973 Program),No.2012CB518504a grant from the National Level Undergraduate Student Innovation Venture Training Project of Local Colleges,No.201212121048a grant from the ThreeStage Key Subject Construction Project of Guangdong Province of China(211 Project),No.(2009)431
文摘Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture atTaichong （LR3） andTaixi （KI3） using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture atTaichong andTaixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic res-onance imaging, which revealed that the amplitude of low-frequency lfuctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus （Brodmann area 18/19）, inferior occipital gyrus （Brodmann area 18） and cuneus （Brodmann area 18）, but decreased mainly in the gyrus rectus of the frontal lobe （Brodmann area 11）, inferi-or frontal gyrus （Brodmann area 44） and the center of the posterior lobe of the cerebellum. The present ifndings indicate that acupuncture atTaichong andTaixi speciifcally promote blood lfow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.
