AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract ...AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.展开更多
In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method...In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.展开更多
Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The st...Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.展开更多
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac...Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.展开更多
The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in orde...The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N_(2) gas during laser powder bed fusion.This is substantialized based on both the thermal diffusion-and chemical reactionbased metallurgy of the Mg_(2)Si–SiC/nitride hybrid composite.This study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive manufacturing.This strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg_(2)Si–SiC/nitride hybrid composite.Consequently,the coefficient of friction of the hybrid composite exhibits a 309.3%decrease to–1.67 compared to–0.54 for the conventional nonreinforced Mg_(2)Si structure,while the tensile strength exhibits a 171.3%increase to 831.5 MPa compared to 485.3 MPa for the conventional structure.This outstanding mechanical behavior is due to the(1)the complementary and synergistic reinforcement effects of the SiC and nitride compounds,each of which possesses an intrinsically high hardness,and(2)the strong adhesion of these compounds to the Mg_(2)Si matrix despite their small sizes and low concentrations.展开更多
目的探讨2型糖尿病周围神经病变与胰岛β细胞功能的相关性。方法选取2020年1月至12月广西医科大学第二附属医院收治的298例2型糖尿病患者为研究对象,根据是否合并周围神经病变将其分为周围神经病变组(n=178)和无周围神经病变组(n=120)...目的探讨2型糖尿病周围神经病变与胰岛β细胞功能的相关性。方法选取2020年1月至12月广西医科大学第二附属医院收治的298例2型糖尿病患者为研究对象,根据是否合并周围神经病变将其分为周围神经病变组(n=178)和无周围神经病变组(n=120)。采用二两馒头餐后30min净增C肽与葡萄糖比值(ΔC肽30/ΔG30)和30min净增胰岛素与葡萄糖比值(Δ胰岛素30/ΔG30)评估早期阶段胰岛分泌功能;采用二两馒头餐后120min血糖曲线下面积(area under the curve,AUC)校正后的C肽和胰岛素AUC(C肽_(AUC)/G_(AUC)、胰岛素_(AUC)/G_(AUC))评估总的β细胞分泌功能。多因素Logistic回归分析探讨2型糖尿病并发周围神经病变的危险因素。结果周围神经病变组患者的餐后60min C肽、120min C肽、ΔC肽30/ΔG30、C肽_(AUC)/G_(AUC)均显著低于无周围神经病变组(P<0.05)。ΔC肽30/ΔG30和C肽_(AUC)/G_(AUC)与高密度脂蛋白胆固醇、空腹血糖、餐后2h血糖、糖化血红蛋白均呈负相关,与体质量指数、尿酸均呈正相关(P<0.05)。多因素Logistic回归分析结果显示,空腹血糖升高、C肽_(AUC)/G_(AUC)降低均是糖尿病患者发生周围神经病变的独立危险因素(P<0.05)。结论2型糖尿病患者胰岛β细胞功能下降是糖尿病周围神经病变发病的独立危险因素,应积极保护胰岛β细胞功能以延缓周围神经病变的发生。展开更多
基金Supported by the Natural Science Foundation of Fujian Province(No.2021J01229)National Key Research and Development Program of China(No.2016YFC1000307).
文摘AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)(No. 2021R1I1A1A0105621313, No. 2022R1F1A1074441, No. 2022K1A3A1A20014496, and No. 2022R1F1A1074083)supported by the Ministry of Education Funding (No. RIS 2021-004)supported by the Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea (RS-2023-00284318).
文摘In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.
文摘Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.
基金financially supported by National Natural Science Foundation of China(81700524)Natural Science Foundation of Fujian Province(2022J01866)from Fujian Provincial Department of Science and Technology+1 种基金Key Project of Fujian University of Traditional Chinese Medicine(X2021019)Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)。
文摘Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
基金supported by the Learning & Academic Research Institution for Master’s and Ph.D. Students and Postdocs (LAMP) Program of the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. RS-2023-00285353)supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2021R1A2C3006662, NRF-2022R1A5A1030054, and 2021R1A2C1091301)+3 种基金the support from Natural Sciences and Engineering Research Council of Canada (NSERC)Canada Foundation for Innovation (CFI)Atlantic Canada Opportunities Agency (ACOA)the New Brunswick Innovation Foundation (NBIF)
文摘The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N_(2) gas during laser powder bed fusion.This is substantialized based on both the thermal diffusion-and chemical reactionbased metallurgy of the Mg_(2)Si–SiC/nitride hybrid composite.This study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive manufacturing.This strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg_(2)Si–SiC/nitride hybrid composite.Consequently,the coefficient of friction of the hybrid composite exhibits a 309.3%decrease to–1.67 compared to–0.54 for the conventional nonreinforced Mg_(2)Si structure,while the tensile strength exhibits a 171.3%increase to 831.5 MPa compared to 485.3 MPa for the conventional structure.This outstanding mechanical behavior is due to the(1)the complementary and synergistic reinforcement effects of the SiC and nitride compounds,each of which possesses an intrinsically high hardness,and(2)the strong adhesion of these compounds to the Mg_(2)Si matrix despite their small sizes and low concentrations.
文摘目的探讨2型糖尿病周围神经病变与胰岛β细胞功能的相关性。方法选取2020年1月至12月广西医科大学第二附属医院收治的298例2型糖尿病患者为研究对象,根据是否合并周围神经病变将其分为周围神经病变组(n=178)和无周围神经病变组(n=120)。采用二两馒头餐后30min净增C肽与葡萄糖比值(ΔC肽30/ΔG30)和30min净增胰岛素与葡萄糖比值(Δ胰岛素30/ΔG30)评估早期阶段胰岛分泌功能;采用二两馒头餐后120min血糖曲线下面积(area under the curve,AUC)校正后的C肽和胰岛素AUC(C肽_(AUC)/G_(AUC)、胰岛素_(AUC)/G_(AUC))评估总的β细胞分泌功能。多因素Logistic回归分析探讨2型糖尿病并发周围神经病变的危险因素。结果周围神经病变组患者的餐后60min C肽、120min C肽、ΔC肽30/ΔG30、C肽_(AUC)/G_(AUC)均显著低于无周围神经病变组(P<0.05)。ΔC肽30/ΔG30和C肽_(AUC)/G_(AUC)与高密度脂蛋白胆固醇、空腹血糖、餐后2h血糖、糖化血红蛋白均呈负相关,与体质量指数、尿酸均呈正相关(P<0.05)。多因素Logistic回归分析结果显示,空腹血糖升高、C肽_(AUC)/G_(AUC)降低均是糖尿病患者发生周围神经病变的独立危险因素(P<0.05)。结论2型糖尿病患者胰岛β细胞功能下降是糖尿病周围神经病变发病的独立危险因素,应积极保护胰岛β细胞功能以延缓周围神经病变的发生。
文摘目的 分析利拉鲁肽治疗冠心病合并2型糖尿病患者的临床效果。方法 102例冠心病合并2型糖尿病患者,应用电脑随机选择方式将患者分为对照组和观察组,每组51例。对照组给予二甲双胍治疗,观察组给予二甲双胍结合利拉鲁肽治疗。对比两组心功能指标(左室射血分数、左室舒张末内径、心排血量以及QT离散度)、血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)]、胰岛素抵抗情况[胰岛β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)]。结果 治疗后,观察组左室射血分数(56.10±9.06)%、左室舒张末内径(45.80±6.64)mm、心排血量(5.60±1.18)L/min、QT离散度(45.03±6.31)ms优于对照组的(50.50±7.90)%、(50.20±7.07)mm、(4.88±1.01)L/min、(53.77±8.50)ms(P<0.05)。治疗后,观察组2 h PG(7.28±1.30)mmol/L、FPG(6.06±0.27)mmol/L、HbA1c(5.88±0.32)%优于对照组的(8.71±1.20)mmol/L、(7.01±0.76)mmol/L、(6.65±0.52)%(P<0.05)。治疗后,观察组HOMA-β、HOMA-IR优于对照组(P<0.05)。结论 结合冠心病合并2型糖尿病患者实际情况应用二甲双胍结合利拉鲁肽治疗,能够有效改善患者的心功能指标、血糖指标及胰岛素抵抗情况,具有优良的应用前景,在今后的工作过程中能够进一步应用。
