Carbamate pesticides, a new type of broad-spectrum pesticides for controlling pests, mites, and weeds, are developed to address the shortcomings of organochlorine and organophosphorus pesticides. Their widespread use and slow degradation have led to environmental pollution, causing damage to ecosystems and human health. Managing pesticide residues is a pressing issue in the current environmental protection. This study aims to investigate the expression of SyEst870, a member of the SGNH/GDSL hydrolase family in Sphingobium yanoikuyae, in a prokaryotic system and evaluate the ability of the recombinant protein to degrade carbamate pesticides. The prokaryotic expression vector pET-32a-SyEst870 was constructed and transformed into the Escherichia coli BL21 for heterologous expression. The purified protein was studied in terms of enzyme activity and effects of temperature, pH, and metal ions on the enzyme activity, with p-nitrophenol acetate as the substrate and based on the standard curve of p-nitrophenol. LC-MS (liquid chromatography-mass spectrometry) was employed to examine the degradation effects of SyEst870 on carbaryl, metolcarb, and isoprocarb. GC-MS (gas chromatography-mass spectrometry) was employed to detect the degradation products of SyEst870 for the three pesticides. The soluble protein SyEst870 was successfully obtained through the heterologous expression in Escherichia coli, which yielded an enzyme with the activity of 677.5 U after affinity chromatography. SyEst870 exhibited degradation rates of 82.34%, 84.43%, and 92.87% for carbaryl, metolcarb, and isoprocarb, respectively, at an initial concentration of 100 mg/L within 24 h at 30 ℃ and pH 7.0. The primary degradation products of carbaryl were identified as α-naphthol and methyl isocyanate. Metolcarb was mainly degraded into m-cresol and methyl isocyanate, and isoprocarb was mainly degraded into 2-isopropylphenol and methyl isocyanate. Compared with the half-life of carbamate pesticides in the natural environment, which ranges from a few days to several weeks, the recombinant protein SyEst870 can rapidly eliminate the residues of carbamate pesticides. This study lays a foundation for addressing pesticide residues in the environment and in fruits and vegetables.
Escherichia coli/metabolism* ; Sphingomonadaceae/genetics* ; Recombinant Proteins/metabolism* ; Biodegradation, Environmental ; Esterases/metabolism* ; Pesticides/isolation & purification* ; Carbamates/isolation & purification*

Objective:To describe the positive rates of high-risk human papillomavirus (HR-HPV) DNA and serum-neutralizing antibody in cervical intraepithelial neoplasia (CIN) tissues of rural women in Xiangyuan County, Shanxi Province, and evaluate the association of HR-HPV DNA and neutralizing antibody positive status with the occurrence of CIN.Methods:In a cohort of 1 897 women aged 35-45 years established by the Shanxi Province Cervical Cancer Screening StudyⅠ, DNA typing (SPF10 PCR-DEIA-LiPA25) was performed by using tissue samples of women with positive HR-HPV test results [Hybrid CaptureⅡ(HC2)] or abnormal cytological or pathological results. Serum HR-HPV neutralizing antibody detection was conducted with multicolor pseudovirion-based neutralization assay. Cochran-Armitage trend test was used to analyze the changing trend of the positive rate of HR-HPV DNA and neutralizing antibody with the progression of CIN. Multivariate logistic regression models were used to evaluate the influence and multiplicative interaction of HR-HPV DNA and neutralizing antibody positive status on the occurrence of CIN. The relative excess risk ( RERI), attributable proportion of interaction ( AP), and the synergy index ( SI) of the interaction were calculated to evaluate the additive interaction of HR-HPV DNA and neutralizing antibody on the occurrence of CIN. Results:The positive rate of any type of HR-HPV DNA (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) in 479 women who were HC2 positive or had abnormal cytological or pathological detection results was 37.16%. In normal, CIN1, CIN2, and CIN3+ groups, the HR-HPV DNA positive rates were 18.03%, 49.53%, 90.24% and 94.59%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 63.88%. In normal, CIN1, CIN2, and CIN3+ groups, the positive rates of HR-HPV neutralizing antibody were 63.95%, 57.94%, 70.73%, and 72.97%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 53.31% in 1 418 women who were HC2 negative and had normal cytopathology, and the most common types were HPV51 (27.36%) and HPV39 (24.96%). Multivariate logistic regression analysis showed that any type of HR-HPV DNA positive status ( OR=9.15, 95% CI: 5.99-14.20, P<0.001) was the independent factor for the occurrence of CIN, HR-HPV neutralizing antibody positive status was not associated with the occurrence of CIN ( OR=0.95, 95% CI: 0.61-1.48, P=0.815). The OR value of the multiplication of HR-HPV DNA and neutralizing antibody positive status of the occurrence of CIN was 1.63 (95% CI: 0.67-3.95), P=0.283. Quantitative analysis of interaction showed that RERI was 1.65 (95% CI:-3.56-6.86), SI was 1.28 (95% CI: 0.58-2.82), and AP was 0.19 (95% CI:-0.36-0.75). Conclusions:HR-HPV DNA positive status was a risk factor for the occurrence of CIN, but neutralizing antibody positive status was not associated with the occurrence of CIN. They had no significant multiplicative or additive interaction with the occurrence of CIN.

Objective:To describe the positive rates of high-risk human papillomavirus (HR-HPV) DNA and serum-neutralizing antibody in cervical intraepithelial neoplasia (CIN) tissues of rural women in Xiangyuan County, Shanxi Province, and evaluate the association of HR-HPV DNA and neutralizing antibody positive status with the occurrence of CIN.Methods:In a cohort of 1 897 women aged 35-45 years established by the Shanxi Province Cervical Cancer Screening StudyⅠ, DNA typing (SPF10 PCR-DEIA-LiPA25) was performed by using tissue samples of women with positive HR-HPV test results [Hybrid CaptureⅡ(HC2)] or abnormal cytological or pathological results. Serum HR-HPV neutralizing antibody detection was conducted with multicolor pseudovirion-based neutralization assay. Cochran-Armitage trend test was used to analyze the changing trend of the positive rate of HR-HPV DNA and neutralizing antibody with the progression of CIN. Multivariate logistic regression models were used to evaluate the influence and multiplicative interaction of HR-HPV DNA and neutralizing antibody positive status on the occurrence of CIN. The relative excess risk ( RERI), attributable proportion of interaction ( AP), and the synergy index ( SI) of the interaction were calculated to evaluate the additive interaction of HR-HPV DNA and neutralizing antibody on the occurrence of CIN. Results:The positive rate of any type of HR-HPV DNA (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) in 479 women who were HC2 positive or had abnormal cytological or pathological detection results was 37.16%. In normal, CIN1, CIN2, and CIN3+ groups, the HR-HPV DNA positive rates were 18.03%, 49.53%, 90.24% and 94.59%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 63.88%. In normal, CIN1, CIN2, and CIN3+ groups, the positive rates of HR-HPV neutralizing antibody were 63.95%, 57.94%, 70.73%, and 72.97%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 53.31% in 1 418 women who were HC2 negative and had normal cytopathology, and the most common types were HPV51 (27.36%) and HPV39 (24.96%). Multivariate logistic regression analysis showed that any type of HR-HPV DNA positive status ( OR=9.15, 95% CI: 5.99-14.20, P<0.001) was the independent factor for the occurrence of CIN, HR-HPV neutralizing antibody positive status was not associated with the occurrence of CIN ( OR=0.95, 95% CI: 0.61-1.48, P=0.815). The OR value of the multiplication of HR-HPV DNA and neutralizing antibody positive status of the occurrence of CIN was 1.63 (95% CI: 0.67-3.95), P=0.283. Quantitative analysis of interaction showed that RERI was 1.65 (95% CI:-3.56-6.86), SI was 1.28 (95% CI: 0.58-2.82), and AP was 0.19 (95% CI:-0.36-0.75). Conclusions:HR-HPV DNA positive status was a risk factor for the occurrence of CIN, but neutralizing antibody positive status was not associated with the occurrence of CIN. They had no significant multiplicative or additive interaction with the occurrence of CIN.

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology* ; Cellular Senescence ; Homeostasis ; Cell Cycle Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; Mitochondria/metabolism* ; Electron Transport Complex III/metabolism* ; Humans ; Cells, Cultured

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).

The diagnosis and treatment of spontaneous rupture and massive hemorrhage of tuberous sclerosis-related renal hamartoma in a woman in the third trimester are reported. The patient was admitted at 39 weeks of gestation, with threatened labor and a history of bilateral renal hamartoma, which had been hidden. Placental abruption was considered due to persistent lumbago, abdominal pain, abdominal muscle tension, uterine tension and fetal heart rate dropping to 90 bpm, and an emergency cesarean section was performed at 39 +1 weeks. About 200 ml of bloody ascites was found in the peritoneal cavity. A live boy was delivered and no blood clot was seen in the maternal face of the placenta. After the uterine incision was closed, a huge bluish purple mass was detected on the right-side retroperitoneum and the renal angiography showed rupture and hemorrhage of a right renal hamartoma. A selective right renal artery embolization was performed. The patient recovered after the operation and was discharged seven days later required by the family. The patient was in good condition except for hematuria during a 30-day postpartum follow-up, and oral everolimus treatment and regular follow-up were continued. The newborn with a birth weight of 2 355 g was transferred to the neonatology department after birth due to severe asphyxia, and postnatal echocardiography suspected heart rhabdomyoma. The baby had one seizure but was otherwise well, and was discharged after eight days. The seizure did not recur to the neonate after discharge. Clinicians should pay attention to pregnant women with renal hamartoma. If abnormal abdominal distension, hematuria or lumbago occur during pregnancy, rupture of renal hamartoma and possible massive hemorrhage should be considered.

Objective: To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods: A case-control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age ≥30 years, body mass index (BMI) <40 kg/m², no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results: The age (mean±SD) of the case and control group was (53.71±11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P₂₅, P₇₅)] in the case group was 92.81(77.07, 107.05) μg/L, which was significantly higher than the control group [88.73 (77.13, 100.88) μg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high-concentration group and the low-concentration group compared with the middle-concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion The study suggested a U-shaped association between plasma selenium and IGR.

Objective To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods A case?control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age≥30 years, body mass index (BMI)<40 kg/m2, no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results The age (mean± SD) of the case and control group was (53.71± 11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P25, P75)] in the case group was 92.81(77.07, 107.05) μg/L, which was significantly higher than the control group [ 88.73 (77.13, 100.88) μg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high?concentration group and the low?concentration group compared with the middle?concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion The study suggested a U?shaped association between plasma selenium and IGR.

Objective To investigate the association between plasma selenium exposure and the risk of impaired glucose regulation (IGR). Methods A case?control study was conducted to select IGR patients who were admitted to the outpatient clinic of the Department of Endocrinology to perform oral glucose tolerance test(OGTT) at the Tongji Hospital affiliated to the Tongji Medical College from September 2004 to 2016 as a case group. Participants with normal glucose tolerance recruited from an unselected group of population undergoing routine health examinations in the same hospital were selected as a control group. The control group was matched according to the age (±5 years old) and sex of the case group. The inclusion criteria for subjects recruited were as follows: age≥30 years, body mass index (BMI)<40 kg/m2, no history of a diagnosis of IGR or type 2 diabetes, and no history of receiving pharmacological treatment for hyperlipidemia or hypertension. Patients with any clinically systemic disease such as neurological or endocrine disease, acute illness, chronic inflammatory disease or infectious disease were excluded from the study. A total of 1 957 subjects, 897 in the case group and 1 060 in the control group, were included. Questionnaires were used to collect information of all subjects, and peripheral venous blood was collected after fasting and OGTT, respectively. Plasma selenium, fasting blood glucose, blood lipid (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol) and 2 h OGTT plasma glucose concentration were detected, respectively. The subjects were divided into low, medium and high concentration groups according to the tertiles of plasma selenium concentration in the control group. The multivariate unconditional logistic regression analysis was performed to analyze the association between plasma selenium exposure and IGR. Results The age (mean± SD) of the case and control group was (53.71± 11.38) and (53.95±12.17) years old. The plasma selenium concentration [M (P25, P75)] in the case group was 92.81(77.07, 107.05) μg/L, which was significantly higher than the control group [ 88.73 (77.13, 100.88) μg/L] (P<0.05). The results of multivariate unconditional logistic regression analysis showed that after adjusting for age, sex, BMI, family history of diabetes and hypertension, the risk of IGR was higher in the high?concentration group and the low?concentration group compared with the middle?concentration group, the values of OR (95%CI) were 1.22 (95%CI: 0.94-1.59) and 1.81 (95%CI: 1.42-2.30), respectively. Conclusion The study suggested a U?shaped association between plasma selenium and IGR.