Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and e...Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.展开更多
The potential utilization and development of the Ba isotope tool depend on an accurateδ^(137/134)Ba determination of the samples.During the chemical purification,whether the adsorption process on the surface of the i...The potential utilization and development of the Ba isotope tool depend on an accurateδ^(137/134)Ba determination of the samples.During the chemical purification,whether the adsorption process on the surface of the ionexchange resin could lead to the Ba isotopic fractionation and the degree of fractionation directly influence the accurateδ^(137/134)Ba determination.In the present work,first-principles calculations based on the density functional theory were used to quantify the Ba isotopic equilibrium fractionation factor between the aqueous solution and the resin in the acid leaching process.By constructing and optimizing the geometric configurations of Ba-containing species,Ba(H_(2)O)_(n)^(2+),Ba(H_(2)O)_(n)Cl_(2),Ba(H_(2)O)_(n)(NO_(3))2,and the adsorbed Ba^(2+)on the surface of the resin,extracting the harmonic vibrational frequencies,we finally at 298 K obtained the fractionations,Δ^(137/134)Ba_(soln-ads)=0.07‰,Δ^(137/134)Ba_(Ba(H_(2)O)_(n)Cl_(2)-ads)=0.05‰,andΔ^(137/134)-Ba^(Ba(H_(2)O)_(n)(NO_(3))2-ads)=0.02‰.Overall,there were almost no Ba isotope fractionations during leaching.Although the Ba isotope fractionation can be magnified by the Rayleigh fractionation process in purification,the difference inδ137/134Ba between the initial and final stages did not exceed0.060‰(or 0.045‰)when leaching the standard sample with HCl or HNO_(3),which is equal to or less than the accuracy of Ba isotopic analysis.At a common yield of89.75%,Ba isotopic fractionation induced by incomplete recovery was 0.015‰for HCl(or 0.011‰for HNO_(3)).Finally,if the influence of an incomplete recovery on theδ137/134Ba determination needs to be ignored,the recovery is suggested to be not less than 67%for HCl(or 46%for HNO_(3)).展开更多
OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine micr...OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.展开更多
Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microgli...Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease.Our results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure susceptibility.In addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss.We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE rats.Notably,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.展开更多
Artificial macrocycle with high binding selectivity in water is often challenging but urgently needed in various research and application areas.Herein,we report a new water-soluble biomimetic tetralactam macrocycle an...Artificial macrocycle with high binding selectivity in water is often challenging but urgently needed in various research and application areas.Herein,we report a new water-soluble biomimetic tetralactam macrocycle and realize the ultra-high selectivity to nucleosides over corresponding monophosphate nucleotides by rational modification.The introduction of charged groups at the periphery of endofunctionalized cavity makes the selectivity(guanosine to guanosine 5-monophosphate)increase remarkably from 100 to 1119.Based on the ultra-high selectivity of biomimetic tetralactam macrocycle,the sensitive CD73 enzyme activity assay was then achieved through product-selective fluorescence indicator displacement assay.Furthermore,the capability of the proposed method for inhibitor screening was successfully displayed.展开更多
Objective:The objective of this study was to investigate the clinical value of the endometrial microbiota test(EMT)combined with personalized treatment in patients with repeated implantation failure(RIF).Methods:From ...Objective:The objective of this study was to investigate the clinical value of the endometrial microbiota test(EMT)combined with personalized treatment in patients with repeated implantation failure(RIF).Methods:From March 2019 to August 2022,the clinical data of patients with RIF at the Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed.A total of 356 patients underwent the EMT using 16S rRNA sequencing and were included in the EMT group.The SPSS statistical software propensity score was set at 1:1 to match the age,anti-Müllerian hormone(AMH),antral follicle count(AFC),years of infertility,and body mass index(BMI)of the women who had not undergone the EMT;subsequently,354 patients were classified in the non-EMT group.We compared the clinical characteristics of the two groups and analyzed the clinical pregnancy outcomes after personalized treatment.Results:The clinical pregnancy rate(CPR)of the EMT group was significantly higher than that of the non-EMT group(47.81%vs.13.38%,P<0.05).Among 356 patients who underwent the EMT,55 patients(15.45%)in group A with normal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis,34 patients(9.55%)in group B with abnormal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis,35 patients(9.83%)in group C with normal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis,and 232 patients(65.17%)in group D with abnormal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis.After administration of probiotics or antibiotic plus probiotics treatment,the pregnancy rates of groups C and D were higher than those of group A(44.00%vs.20.00%and 55.03%vs.20.00%,respectively;bothP<0.05).Conclusion:The EMT combined with personalized treatment in patients with RIF has solid clinical value as a new treatment strategy.展开更多
The intensification of energy crises and environmental pollution inspire researchers’attention to environment-friendly SnTe thermoelectric materials.In this work,we achieved a lower lattice thermal conductivity and o...The intensification of energy crises and environmental pollution inspire researchers’attention to environment-friendly SnTe thermoelectric materials.In this work,we achieved a lower lattice thermal conductivity and optimized the power factor via the synergistic optimization of bonding characteristic,VSn,and resonant level for the SnTe system,respectively.Pb-introduction produces weak bonding strength,mass fluctuation,and stress distortion,which result in lower thermal conductivity.The lowest lattice thermal conductivity achieves 0.66 W m^(–1) K^(–1) at 773 K.Further introduced VSn relieves loss of electrical conductivity caused by Pb-introduction,and it also makes the bigger g(E)and up-shift of resonance level.The VSn,enhanced g(E),and resonant level make electrical conductivity and Seebeck coefficient enhance simultaneously.Finally,the further optimization of thermal and electronic transport performance contributes to a higher ZT value of∼0.86 at 773 K in the Sn_(0.685)Pb_(0.285)In_(0.015)Te_(0.7)Se_(0.3) sample.The strategy of bonding characteristic,VSn,and resonant level synergistic engineering will be widely applicable to various TE systems for achieving better thermoelectric performance.展开更多
Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration ...Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen （CEE） and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women. Methods： A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups： Group A received CEE 0.3 mg/micronized progesterone （MP） 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student＇s t-test and analysis of variance. Results： A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline （all P 〈 0.05）. Among the three groups, only Group C showed significantly increased triglycerides compared with baseline （ 1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P 0.026）. Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups. Conclusions： Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.展开更多
Background:Obesity and insulin resistance(IR)are common features of polycystic ovary syndrome(PCOS).Metformin(MET)increases insulin sensitivity,but it is associated with unsatisfactory weight loss.The glucagon-like pe...Background:Obesity and insulin resistance(IR)are common features of polycystic ovary syndrome(PCOS).Metformin(MET)increases insulin sensitivity,but it is associated with unsatisfactory weight loss.The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes.This study aimed to explore the therapeutic effects of exenatide once-weekly(QW)combined with MET on body weight,as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups:MET(500 mg three times a day[TID])or combination treatment(COM)(MET 500 mg TID,exenatide 2 mg QW)for 12 weeks.The primary outcomes were anthropometric changes associated with obesity,and the secondary outcomes included changes in reproductive hormone levels,glucose and lipid metabolism,and C-reactive protein.Results:Forty(80%)patients completed the study.COM therapy was superior to MET monotherapy in reducing weight(P=0.045),body mass index(BMI)(P=0.041),and waist circumference(P=0.023).Patients in the COM group on an average lost 3.8±2.4 kg compared with 2.1±3.0 kg in the MET group.In the COM group,BMI and waist circumference decreased by 1.4±0.87 kg/m2 and 4.63±4.42 cm compared with 0.77±1.17 kg/m2 and 1.72±3.07 cm in the MET group,respectively.Moreover,levels of fasting glucose,oral glucose tolerance test(OGTT)2-h glucose,and OGTT 2-h insulin were significantly lower with COM therapy than with MET(P<0.050).Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusions:COM therapy was more effective than MET alone in reducing body weight,BMI,and waist circumference,and improving insulin sensitivity in overweight/obese women with PCOS,with acceptable short-term side effects.展开更多
Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebra...Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.展开更多
Objective:To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome(PCOS)after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)...Objective:To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome(PCOS)after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET).Methods:This was a retrospective cohort study on 2,231 PCOS patients undergoing IVF/ICSI treatment.For comparison,we enrolled another 2,231 patients with tubular factors in control group.Spontaneous abortion rate and chromosomal abnormality rate were compared between the two groups.Furthermore,clinical data were compared between the patients with spontaneous abortion and those with ongoing pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients.Results:Patients in the PCOS group had significantly higher spontaneous abortion rate(24.15%)than that in the control group(12.75%,P<0.001).Chromosomal abnormality rate was significantly lower in the PCOS group(36.05%,31/86)than in the control group(55.56%,50/90,P=0.009).In the PCOS group,patients with spontaneous abortion had significantly elder age,higher body mass index(BMI),and homeostasis model assessment for insulin resistance(HOMA-IR)than those with ongoing pregnancy.The logistic regression analysis confirmed that the age,BMI,and HOMA-IR were the risk factors of spontaneous abortion in the PCOS patients.There were no significant differences between groups in the type of cycles,the quality of embryos transferred,the number of embryos transferred,fasting blood glucose,fasting insulin,and so on.Conclusions:Compared with non-PCOS patients,PCOS patients had higher spontaneous abortion rate,but the chromosomal abnormality was not a major factor for the high spontaneous abortion rate in the PCOS patients.Age,BMI,and HOMA-IR were risk factors for spontaneous abortion after IVF/ICSI-ET in PCOS patients.展开更多
Ovulation-induction refers to the type of ovarian stimulation for anovulatory women aimed at restoring normal fertility by generating normal ovulatory cycles and inducing single dominant follicle selection and ovulati...Ovulation-induction refers to the type of ovarian stimulation for anovulatory women aimed at restoring normal fertility by generating normal ovulatory cycles and inducing single dominant follicle selection and ovulation. In China, a great number of women with ovulatory disorders are treated by obstetricians and gynecologists (ob-gyns) who are not specialized in infertility. The aim of this study was to investigate the self-reported ob-gyns proficiency of ovulation induction and the most commonly used drug for this procedure.展开更多
基金supported by the National Key Research and Development Program of China (2021YFA0805902,2022YFF0710703)National Natural Science Foundation of China (32201257)+1 种基金Science and Technology Innovation Project of Xiongan New Area (2022XAGG0121)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)。
文摘Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.
基金financially supported by the Hebei Natural Sciences Foundation(Grant Nos.D2020402004 and D2021402020)Hebei Education Department Key Program(Grant No.ZD2018086)+1 种基金the State Natural Sciences Foundation(Grant No.41603011)Hebei University of Engineering Doctoral Special Program(Grant Nos.17129033019 and 17129033020)。
文摘The potential utilization and development of the Ba isotope tool depend on an accurateδ^(137/134)Ba determination of the samples.During the chemical purification,whether the adsorption process on the surface of the ionexchange resin could lead to the Ba isotopic fractionation and the degree of fractionation directly influence the accurateδ^(137/134)Ba determination.In the present work,first-principles calculations based on the density functional theory were used to quantify the Ba isotopic equilibrium fractionation factor between the aqueous solution and the resin in the acid leaching process.By constructing and optimizing the geometric configurations of Ba-containing species,Ba(H_(2)O)_(n)^(2+),Ba(H_(2)O)_(n)Cl_(2),Ba(H_(2)O)_(n)(NO_(3))2,and the adsorbed Ba^(2+)on the surface of the resin,extracting the harmonic vibrational frequencies,we finally at 298 K obtained the fractionations,Δ^(137/134)Ba_(soln-ads)=0.07‰,Δ^(137/134)Ba_(Ba(H_(2)O)_(n)Cl_(2)-ads)=0.05‰,andΔ^(137/134)-Ba^(Ba(H_(2)O)_(n)(NO_(3))2-ads)=0.02‰.Overall,there were almost no Ba isotope fractionations during leaching.Although the Ba isotope fractionation can be magnified by the Rayleigh fractionation process in purification,the difference inδ137/134Ba between the initial and final stages did not exceed0.060‰(or 0.045‰)when leaching the standard sample with HCl or HNO_(3),which is equal to or less than the accuracy of Ba isotopic analysis.At a common yield of89.75%,Ba isotopic fractionation induced by incomplete recovery was 0.015‰for HCl(or 0.011‰for HNO_(3)).Finally,if the influence of an incomplete recovery on theδ137/134Ba determination needs to be ignored,the recovery is suggested to be not less than 67%for HCl(or 46%for HNO_(3)).
基金supported by National Natural Science Foundation of China(81671188)Zhejiang Provincial Natural Science Foundation of China(LY12H31010)the Key Laboratory of Hangzhou City Project(20090233T12)
文摘OBJECTIVE We have recently reported that cysteinyl leukotriene(Cys LT) signaling plays an important role in microglial interleukin(IL)-1β secretion and subsequent neurotoxicity.The present study aimed to examine microglial morphological changes and the upstream molecular underlying IL^(-1)β production in Cys LT receptor agonist leukotriene D4(LTD4)-treated BV2 microglia in vitro.METHODS Twenty-four hours after murine microglial BV2 cells were stimulated with LTD4(1-100 nmol·L^(-1)),the cell proliferation and morphology were observed.The expression level of cysteinyl aspartate-specific protease 1(CASP1) protein was measured by Western blotin BV2 cells.In addition,BV2 cells were pretreated with or without CysLT1 receptor antagonist montelukast for 1 h and the effects of monte-lukaston LTD4-stimulated microglial activation and CASP1 expression were evaluated.RESULTS The number of BV2 cells had an increasing tendency after 24 h treatment with LTD4,but no significant differences were observed between the control and LTD4-treated cells(P>0.05).Under basal and resting conditions,BV2 microglial cells displayed a ramified morphology.However,LTD4 at 100 nmool·L^(-1) drove microglial morphological changes from a ramified towards an amoeboid shape.The expression of CASP1 protein was significantly upregulated in 100 nmool·L^(-1) LTD4-treated BV2 microglia(P<0.01).Furthermore,pretreatment with CysLT1 receptor antagonist montelukast prevented cell morphological changes and suppressed the increased CASP1 expression in LTD4-treated BV2 cells(P<0.05).CONCLUSION Cys LT receptor agonist LTD4 induces morphological changes and CASP1 expressionin BV2 microglia,which can be inhibited by CysLT1 antagonist.These results suggest the involvement of Cys LT signaling in microglial morphological changes and CASP1 expression.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2019zx09301102)the Project of Liaoning Provincial Department of Education(LJKZ0826)the Open Project of National and Local Joint Engineering Research Center for Drug Research and Development of Neurodegenerative Diseases(2022GCYJZX-YB02).
文摘Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease.Our results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure susceptibility.In addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss.We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE rats.Notably,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.
基金financially supported by National Natural Science Foundation of China(Nos.22174059 and 22201128)Hunan Provincial Natural Science Foundation of China(Nos.2022JJ40363,2022JJ40365 and 2022RC1230)+1 种基金the Excellent youth funding of Hunan Provincial Education Department(No.22B0460)China Postdoctoral Science Foundation(No.2022M721542)。
文摘Artificial macrocycle with high binding selectivity in water is often challenging but urgently needed in various research and application areas.Herein,we report a new water-soluble biomimetic tetralactam macrocycle and realize the ultra-high selectivity to nucleosides over corresponding monophosphate nucleotides by rational modification.The introduction of charged groups at the periphery of endofunctionalized cavity makes the selectivity(guanosine to guanosine 5-monophosphate)increase remarkably from 100 to 1119.Based on the ultra-high selectivity of biomimetic tetralactam macrocycle,the sensitive CD73 enzyme activity assay was then achieved through product-selective fluorescence indicator displacement assay.Furthermore,the capability of the proposed method for inhibitor screening was successfully displayed.
文摘Objective:The objective of this study was to investigate the clinical value of the endometrial microbiota test(EMT)combined with personalized treatment in patients with repeated implantation failure(RIF).Methods:From March 2019 to August 2022,the clinical data of patients with RIF at the Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed.A total of 356 patients underwent the EMT using 16S rRNA sequencing and were included in the EMT group.The SPSS statistical software propensity score was set at 1:1 to match the age,anti-Müllerian hormone(AMH),antral follicle count(AFC),years of infertility,and body mass index(BMI)of the women who had not undergone the EMT;subsequently,354 patients were classified in the non-EMT group.We compared the clinical characteristics of the two groups and analyzed the clinical pregnancy outcomes after personalized treatment.Results:The clinical pregnancy rate(CPR)of the EMT group was significantly higher than that of the non-EMT group(47.81%vs.13.38%,P<0.05).Among 356 patients who underwent the EMT,55 patients(15.45%)in group A with normal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis,34 patients(9.55%)in group B with abnormal endometrial microbiota composition did not test positive for the pathogenic bacteria causing chronic endometritis,35 patients(9.83%)in group C with normal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis,and 232 patients(65.17%)in group D with abnormal endometrial microbiota composition tested positive for the pathogenic bacteria causing chronic endometritis.After administration of probiotics or antibiotic plus probiotics treatment,the pregnancy rates of groups C and D were higher than those of group A(44.00%vs.20.00%and 55.03%vs.20.00%,respectively;bothP<0.05).Conclusion:The EMT combined with personalized treatment in patients with RIF has solid clinical value as a new treatment strategy.
基金supported by the National Natural Science Foundation of China(Nos.U2106216,51971121)the Natural Science Foundation of Shandong Province(Grant No.ZR2020ME012)。
文摘The intensification of energy crises and environmental pollution inspire researchers’attention to environment-friendly SnTe thermoelectric materials.In this work,we achieved a lower lattice thermal conductivity and optimized the power factor via the synergistic optimization of bonding characteristic,VSn,and resonant level for the SnTe system,respectively.Pb-introduction produces weak bonding strength,mass fluctuation,and stress distortion,which result in lower thermal conductivity.The lowest lattice thermal conductivity achieves 0.66 W m^(–1) K^(–1) at 773 K.Further introduced VSn relieves loss of electrical conductivity caused by Pb-introduction,and it also makes the bigger g(E)and up-shift of resonance level.The VSn,enhanced g(E),and resonant level make electrical conductivity and Seebeck coefficient enhance simultaneously.Finally,the further optimization of thermal and electronic transport performance contributes to a higher ZT value of∼0.86 at 773 K in the Sn_(0.685)Pb_(0.285)In_(0.015)Te_(0.7)Se_(0.3) sample.The strategy of bonding characteristic,VSn,and resonant level synergistic engineering will be widely applicable to various TE systems for achieving better thermoelectric performance.
文摘Background： Menopausal hormone therapy （MHT） has been proven to have beneficial effects on several components of metabolic syndrome. However, the effects vary according to different regimens, dosages, and duration of MHT. The aim of the study was to evaluate the effect of standard-dose 0.625 mg conjugated equine estrogen （CEE） and half-dose 0.3 mg CEE daily with different progestogens in a continuous sequential regimen on postmenopausal metabolic parameters in generally healthy postmenopausal women. Methods： A prospective, open-label, randomized controlled clinical trial was conducted between February 2014 and December 2015. Totally 123 Chinese postmenopausal women with climacteric symptoms were included in this study and were randomly assigned to three groups： Group A received CEE 0.3 mg/micronized progesterone （MP） 100 mg daily; Group B received CEE 0.625 mg/MP 100 mg daily; and Group C received CEE 0.625 mg/dydrogesterone 10 mg daily. Drugs were given in a continuous sequential pattern. The duration of treatment was 12 months. Clinical, anthropometrical, and metabolic variables were measured. Data were analyzed according to intention-to-treat analysis, using Student＇s t-test and analysis of variance. Results： A total of 107 participants completed the 12-month follow-up and were included in the data analysis. At 12 months of treatment, high-density lipoprotein cholesterol and apolipoprotein A significantly increased, and low-density lipoprotein cholesterol, fasting glucose, and glycosylated hemoglobin significantly decreased in Groups B and C, compared with baseline （all P 〈 0.05）. Among the three groups, only Group C showed significantly increased triglycerides compared with baseline （ 1.61 ± 0.80 mmol/L vs. 1.21 ± 0.52 mmol/L, P 0.026）. Each group showed a neutral effect on total cholesterol, lipoprotein A, apolipoprotein B, and fasting insulin levels. No cardiovascular and venous thromboembolic events occurred in the three groups. Conclusions： Among Chinese postmenopausal women, half-dose CEE was not sufficient to induce a favorable lipid and carbohydrate profile compared with standard-dose CEE. Adding natural MP may counterbalance the TG-increasing effect of CEE.
文摘Background:Obesity and insulin resistance(IR)are common features of polycystic ovary syndrome(PCOS).Metformin(MET)increases insulin sensitivity,but it is associated with unsatisfactory weight loss.The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes.This study aimed to explore the therapeutic effects of exenatide once-weekly(QW)combined with MET on body weight,as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups:MET(500 mg three times a day[TID])or combination treatment(COM)(MET 500 mg TID,exenatide 2 mg QW)for 12 weeks.The primary outcomes were anthropometric changes associated with obesity,and the secondary outcomes included changes in reproductive hormone levels,glucose and lipid metabolism,and C-reactive protein.Results:Forty(80%)patients completed the study.COM therapy was superior to MET monotherapy in reducing weight(P=0.045),body mass index(BMI)(P=0.041),and waist circumference(P=0.023).Patients in the COM group on an average lost 3.8±2.4 kg compared with 2.1±3.0 kg in the MET group.In the COM group,BMI and waist circumference decreased by 1.4±0.87 kg/m2 and 4.63±4.42 cm compared with 0.77±1.17 kg/m2 and 1.72±3.07 cm in the MET group,respectively.Moreover,levels of fasting glucose,oral glucose tolerance test(OGTT)2-h glucose,and OGTT 2-h insulin were significantly lower with COM therapy than with MET(P<0.050).Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusions:COM therapy was more effective than MET alone in reducing body weight,BMI,and waist circumference,and improving insulin sensitivity in overweight/obese women with PCOS,with acceptable short-term side effects.
基金supported by the National Natural Science Foundation of China(81273491, 81072618,30772561 and 30873053)the Natural Science Foundation of Zhejiang Province,China(Y2090069)+1 种基金the"Qianjiang Rencai Research Plan"of Zhejiang Province China(2010R10055)the Fundamental Research Funds for the Central Universities,China(2009QNA7008)
文摘Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.
基金support from National Key R&D Plan(2017YFC1001600)National Natural Science Foundation of China(81471507).
文摘Objective:To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome(PCOS)after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET).Methods:This was a retrospective cohort study on 2,231 PCOS patients undergoing IVF/ICSI treatment.For comparison,we enrolled another 2,231 patients with tubular factors in control group.Spontaneous abortion rate and chromosomal abnormality rate were compared between the two groups.Furthermore,clinical data were compared between the patients with spontaneous abortion and those with ongoing pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients.Results:Patients in the PCOS group had significantly higher spontaneous abortion rate(24.15%)than that in the control group(12.75%,P<0.001).Chromosomal abnormality rate was significantly lower in the PCOS group(36.05%,31/86)than in the control group(55.56%,50/90,P=0.009).In the PCOS group,patients with spontaneous abortion had significantly elder age,higher body mass index(BMI),and homeostasis model assessment for insulin resistance(HOMA-IR)than those with ongoing pregnancy.The logistic regression analysis confirmed that the age,BMI,and HOMA-IR were the risk factors of spontaneous abortion in the PCOS patients.There were no significant differences between groups in the type of cycles,the quality of embryos transferred,the number of embryos transferred,fasting blood glucose,fasting insulin,and so on.Conclusions:Compared with non-PCOS patients,PCOS patients had higher spontaneous abortion rate,but the chromosomal abnormality was not a major factor for the high spontaneous abortion rate in the PCOS patients.Age,BMI,and HOMA-IR were risk factors for spontaneous abortion after IVF/ICSI-ET in PCOS patients.
基金a grant from The National Natural Science Foundation of China(No.11471024).
文摘Ovulation-induction refers to the type of ovarian stimulation for anovulatory women aimed at restoring normal fertility by generating normal ovulatory cycles and inducing single dominant follicle selection and ovulation. In China, a great number of women with ovulatory disorders are treated by obstetricians and gynecologists (ob-gyns) who are not specialized in infertility. The aim of this study was to investigate the self-reported ob-gyns proficiency of ovulation induction and the most commonly used drug for this procedure.
