m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis.

BACKGROUND: As the most important modifications on the RNA level, N6-methyladenosine (m6A-) and 5-methylcytosine (m5C-) modification could have a direct influence on the RNAs. Long non-coding RNAs (lncRNAs) could also be modified by methylcytosine modification. Compared with mRNAs, the function of lncRNAs could be more potent to some extent in biological processes like tumorigenesis. Until now, rare reports have been done associated with cutaneous melanoma. Herein, we wonder if the m6A- and m5C- modified lncRNAs could influence the immune landscape and prognosis in melanoma, and we also want to find some lncRNAs which could directly affect the malignant behaviors of melanoma. METHODS: Systematically, we explored the expression pattern of m6A- and m5C- modified lncRNAs in melanoma from datasets including UCSC Xena and NCBI GEO, and the prognostic lncRNAs were selected. Then, according to the expression pattern of lncRNAs, melanoma samples from these datasets were divided into several subtypes. Prognostic model, nomogram survival model, drug sensitivity, GO, and KEGG pathway analysis were performed. Furthermore, among several selected lncRNAs, we identified one lncRNA named LINC00893 and investigated its expression pattern and its biological function in melanoma cell lines. RESULTS: We identified 27 m6A- and m5C- related lncRNAs which were significantly associated with survival, and we made a subtype analysis of melanoma samples based on these 27 lncRNAs. Among the two subtypes, we found differences of immune cells infiltration between these two subtypes. Then, LASSO algorithm was used to screen the optimized lncRNAs combination including ZNF252P-AS1, MIAT, FAM13A-AS1, LINC-PINT, LINC00893, AGAP2-AS1, OIP5-AS1, and SEMA6A-AS1. We also found that there was a significant correlation between the different risk groups predicted based on RS model and the actual prognosis. The nomogram survival model based on independent survival prognostic factors was also constructed. Besides, sensitivity to chemotherapeutic agents, GO and KEGG analysis were performed. In different risk groups, a total of 14 drug molecules with different distributions were obtained, which included AZD6482, AZD7762, AZD8055, camptothecin, dasatinib, erlotinib, gefitinib, gemcitabine, GSK269962A, nilotinib, rapamycin, and sorafenib. A total of 55 significantly related biological processes and 17 KEGG signaling pathways were screened. At last, we noticed that LINC00893 had a relatively lower expression in melanoma tissue and cell lines compared with adjacent tissues and epidermal melanocyte, and down-regulation of LINC00893 could promote the malignant behavior of melanoma cells in A875 and MV3. In these two melanoma cell lines, down-regulation of m6A-related molecules like YTHDF3 and METTL3 could promote the expression of LINC00893. CONCLUSION: We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis.

Construction of a Nomogram Model to Identify Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Approximately 50.0% of patients with type 2 diabetes mellitus (T2DM) experience macrovascular diseases, and nearly 80.0% of them succumb to macrovascular complications. Atherosclerotic cardiovascular disease (ASCVD) ranks among the most prevalent macrovascular complications in T2DM. In this study, we aim to develop a nomogram model for the early detection of ASCVD in T2DM patients, enabling us to provide valuable recommendations for the clinical prevention and management of macrovascular complications in this patient population. METHODS: This retrospective analysis encompassed 2620 T2DM patients admitted between June 2015 and June 2021. The cohort comprised 1270 T2DM patients with coexisting ASCVD (referred to as the "ASCVD group") and 1350 individuals who did not experience ASCVD (the "non-ASCVD group"). We conducted a comparative assessment of their baseline characteristics and clinical data. A nomogram model for the identification of ASCVD in T2DM patients was constructed utilizing Logistic regression analysis and the R package. The model's performance was evaluated through receiver operating characteristic (ROC) curve analysis and calibration curves. RESULTS: We developed a nomogram model for the identification of ASCVD in T2DM patients, incorporating ten variables: sex, age, hypertension, smoking history, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio, alanine transaminase (ALT), adenosine deaminase (ADA), postprandial 2-hour C-peptide, monocyte count (MONO), and eosinophil count (EOS). ROC curves demonstrated that the area under the curve (AUC) of the nomogram model for identifying ASCVD in T2DM patients was 0.673 for the training dataset (with a cut-off value of 0.473, specificity of 0.629, and sensitivity of 0.637) and 0.655 for the validation dataset (with a cut-off value of 0.460, specificity of 0.605, and sensitivity of 0.675). The calibration curve indicated a substantial agreement between the predicted and observed cases of ASCVD in the training dataset and an acceptable level of agreement in the validation dataset. CONCLUSIONS: The nomogram model effectively identifies ASCVD in T2DM patients, which can be instrumental in pinpointing the high-risk population for ASCVD among T2DM patients and facilitating timely clinical management.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

Cadmium exposure is associated with decreased muscle strength in middle-aged and older adults.

Cadmium, a toxic heavy metal, is ubiquitous in the environment. No previous research has evaluated the relationship of blood and urine cadmium levels with muscle strength measured by isokinetic knee extensor strength. This analysis included participants who were aged 50 years or older and had measurements of cadmium in blood (n = 2052) and urine (n = 811) from the National Health and Nutrition Examination Survey. Blood and urine cadmium levels were assessed by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry, respectively. Isokinetic dynamometry was used to assess knee extensor strength (peak force). Linear regression models were used to examine the association between cadmium exposure and peak force, with adjustment for potential confounders. The median values (25-75th percentiles) of blood cadmium and creatinine-corrected urine cadmium were 0.50 µg/L (0.40-0.70) and 0.43 µg/g (0.27-0.71), respectively. After adjusting for potential confounders, linear dose-response relationships of peak force with blood and urine cadmium concentrations were observed in the present study. Compared to participants in the highest quartile of blood cadmium and urine cadmium, the peak force decreased by 6.99 Newton (95% CI: -21.96, 7.98) and 26.84 Newton (95% CI: -44.34, -9.34) in participants in the lowest quartiles, respectively. The observed associations were more evident among men participants. Our findings suggest that the cadmium levels have a dose response relationship with decreased muscle strength measured by isokinetic knee extensor strength in middle aged and older adults. Further longitudinal investigations are required to disentangle these complexities on this issue.

NLRP3 mediates the neuroprotective effects of SVHRSP derived from scorpion venom in rotenone-induced experimental Parkinson's disease model.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, scorpion is used to treat diseases with symptoms such as trembling, convulsion and dementia. Our laboratory employs patented technology to extract and purify the active single component from scorpion venom. We then utilize mass spectrometry to determine the amino acid sequence of the polypeptide and synthesize it artificially to acquire the polypeptide with a purity of 99.3%, named SVHRSP (Scorpion Venom Heat-Resistant Peptide). SVHRSP has been demonstrated to display potent neuroprotective efficacy in Parkinson's disease. AIM OF THE STUDY: To explore the molecular mechanisms and potential molecular targets of SVHRSP-afforded neuroprotection in PD mouse models, as well as to investigate the role of NLRP3 in SVHRSP-mediated neuroprotection. MATERIALS AND METHODS: The PD mouse model was induced by rotenone and the neuroprotective role of SVHRSP on the PD mouse model was measured using the gait test, rotarod test, the number of dopaminergic neurons, and the activation of microglia. RNA sequencing and GSEA analysis were performed to find the differentially biological pathways regulated by SVHRSP. Primary mid-brain neuron-glial cultures and NLRP3-/- mice were applied to verify the role of NLRP3 by using qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA) and immunostaining. RESULTS: SVHRSP-afforded dopaminergic neuroprotection was accompanied with inhibition of microglia-mediated neuroinflammatory pathways. Importantly, depletion of microglia markedly reduced the neuroprotective efficacy of SVHRSP against rotenone-induced dopaminergic neurotoxicity in vitro. SVHRSP inhibited microglial NOD-like receptor pathway, mRNA expression and protein level of NLRP3 in rotenone PD mice. SVHRSP also reduced rotenone-induced caspse-1 activation and IL-1ß maturation, indicating that SVHRSP mitigated activation of NLRP3 inflammasome. Moreover, inactivation of NLRP3 inflammasome by MCC950 or genetic deletion of NLRP3 almost abolished SVHRSP-afforded anti-inflammatory, neuroprotective effects and improvement of motor performance in response to rotenone. CONCLUSIONS: NLRP3 mediated the neuroprotective effects of SVHRSP in rotenone-induced experimental PD model, providing additional evidence for the mechanisms of SVHRSP-afforded anti-inflammatory and neuroprotective effects in PD.

Exposure to Metal Mixtures and Overweight or Obesity Among Chinese Adults.

Previous research has investigated the association between individual metal exposure and overweight/obesity (OW/OB). However, there is limited data about metal mixture exposure and OW/OB. This study aimed to explore the individual and joint effects of 21 metals on OW/OB and its metabolic phenotypes. A total of 4042 participants were enrolled in our study, and 51.0% of them were overweight/obese. We quantified 21 metal levels in the urine sample. OW/OB was defined as BMI ≥ 24 kg/m2, while the metabolic phenotypes, including metabolic unhealthy overweight/obesity (MUOW/OB) and metabolic health overweight/obesity (MHOW/OB), were determined by BMI and metabolic state. We used logistic regression to analyze the effect of individual metal exposure on OW/OB and its metabolic phenotypes. Quantile g-computation was applied to evaluate the joint effect of metal exposure on OW/OB and its metabolic phenotypes. In logistic regression, zinc (Zn) was positively associated with OW/OB, with the odds ratio (OR) in the highest quartiles of 2.19 (95% confidence interval (CI), 1.74, 2.77; P trend < 0.001), while arsenic (As) and cadmium (Cd) were negatively associated with OW/OB (OR = 0.70 (0.56, 0.87) and 0.61 (0.48, 0.78), respectively). After adjustment for age, gender, education, cigarette smoking, alcohol drinking, physical activity, meat intake, and vegetable intake, Zn was positively associated with MUOW/OB, while As, Cd, nickel (Ni), and strontium (Sr) were negatively associated with MUOW/OB (all P trend < 0.05). Quantile g-computation showed a significantly negative association between metal mixture exposure and MUOW/OB. Our study suggested that metal mixture exposure might be negatively associated with OW/OB, particularly with MUOW/OB. Zn, As and Cd contributed most to the effect of the mixture. More prospective studies are warranted to confirm these findings and reveal the underlying mechanisms.

Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis.

BACKGROUND: Air pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown. Our objective was to explore the associations of air pollutants with IPF risk and further assess the modification effect of genetic susceptibility. METHODS: We used land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NO x ) and particulate matter (fine particulate matter with diameter <2.5 µm (PM2.5) and particulate matter with diameter <10 µm (PM10)). The polygenic risk score (PRS) was constructed using 13 independent single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated. RESULTS: Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45 per 100 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios of IPF for each interquartile range increase in NO2, NO x and PM2.5 were 1.11 (95% CI 1.03-1.19), 1.07 (95% CI 1.01-1.13) and 1.09 (95% CI 1.02-1.17), respectively. PM2.5 had the highest population attribution risk, followed by NO x and NO2. There were additive interactions between NO2, NO x and PM2.5 and genetic susceptibility. Participants with a high PRS and high air pollution had the highest risk of incident IPF compared with those with a low PRS and low air pollution (adjusted hazard ratio: NO2 3.94 (95% CI 2.77-5.60), NO x 3.08 (95% CI 2.21-4.27), PM2.5 3.65 (95% CI 2.60-5.13) and PM10 3.23 (95% CI 2.32-4.50)). CONCLUSION: Long-term exposures to air pollutants may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.

Associations of mobile phone addiction with suicide ideation and suicide attempt: findings from six universities in China.

Background: Mobile phones are becoming indispensable for life and have changed various aspects of people's lives. The psychological impacts of excessive mobile phone use have emerged as an impressive problem among college students. However, little is known about the associations of mobile phone addiction with suicide ideation and suicide attempt. Methods: A cross-sectional study was conducted with students from six universities in 2022. We collected the socio-demographic characteristics, suicide ideation, suicide attempt, psychosocial factors (depressive symptoms, social support, sleep quality), and health-related characteristics (smoking, drinking, body mass index). Mobile phone addiction was ascertained by the Mobile Phone Addiction Tendency Scale (MPATS). The associations of mobile phone addiction with suicide ideation and suicide attempt were estimated using binary logistic regression and restricted cubic splines regression. Results: A total of 18,723 college students [6,531 males (34.9%) and 12,192 females (65.1%)] were included in the final analysis. Eleven percent of participants had a history of suicide ideation, and 1.8% of participants had engaged in suicide attempt. A total of 5,553 students (29.7%) met the criteria of mobile phone addiction (MPATS score ≥48), and the average score on the MPATS was 39.5 ± 13.0. After adjustment for potential covariates, mobile phone addiction was significantly associated with increased odds of suicide ideation (OR, 1.70; 95% CI, 1.53-1.88) and suicide attempt (OR, 1.48; 95% CI, 1.18-1.86). Gender did not affect the associations of mobile phone addiction with suicide ideation and suicide attempt (P for interaction > 0.05). The restricted cubic splines regression displayed a nonlinear dose-response association between MPATS score and risk of suicide ideation (P for non-linearity < 0.001), while a monotonically increasing risk of suicide attempt was found to be associated with an increasing MPATS score (P for non-linearity = 0.420). Conclusions: Mobile phone addiction is associated with suicide ideation and suicide attempt among college students. The findings indicate that early examination, prevention, and intervention for mobile phone addiction may benefit the prevent and control of suicide.

Relationship between body roundness index and the risk of heart failure in Chinese adults: the Kailuan cohort study.

AIMS: Body roundness index (BRI) is an obesity-related anthropometric index that combines waist circumference and height to better reflect body fat. This study aims to prospectively explore the relationship between BRI and the risk of heart failure (HF) based on a community-based cohort. METHODS AND RESULTS: A total of 140 362 individuals without tumour and HF at baseline were included from the Kailuan cohort study. Their demographic information, anthropometric parameters, and biochemical indexes were collected or measured. The participants were followed up until 31 December 2016 or death or diagnosed with HF, whichever came first. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HF. Restricted cubic spline analysis was applied to further evaluate the possible non-linear dose-response relationship between BRI and the risk of HF. After a median follow-up period of 9.84 years, we identified 1990 HF events. The participants were grouped into four groups according to the quartiles of BRI (Q1: ≤2.93, Q2: 2.93-3.59, Q3: 3.59-4.38, and Q4: ≥4.38). After adjustment for potential confounders, compared with the group of participants in the lowest quartile of BRI, the adjusted HRs (95%CI) were 1.03 (95%CI: 0.87-1.22), 1.27 (95%CI: 1.07-1.49), and 1.50 (95%CI: 1.26-1.78) for subjects in the Q2, Q3, and Q4 groups, respectively. With each standard deviation (here is 1.10) of BRI increasing, the risk of HF increased by 18% (HR: 1.18, 95%CI: 1.12-1.24). Subgroup analysis indicated that the association between BRI and HF was more prominent in younger people (HR: 2.94, 95%CI: 1.80-4.80) than older (HR: 1.89, 95%CI: 1.57-2.27) (P for interaction < 0.001). A significant linear dose-response relationship between BRI and HF was also observed (P for non-linearity = 0.730). CONCLUSIONS: Our study suggests that higher BRI is associated with an increased risk of HF. If these findings can be replicated in other populations, future studies need to examine whether lowering the BRI may lower the risk of incident HF.

Metabolic syndrome severity score and the progression of CKD.

BACKGROUND: Metabolic syndrome severity, expressed by the continuous metabolic syndrome risk score (MetS score), has been demonstrated to be able to predict future health conditions. However, little is known about the association between MetS score and renal function. METHODS: A total of 22,719 participants with normal renal function abstracted from the Kailuan Study were followed from 2006 to 2016. The new onset of chronic kidney disease (CKD) was defined as eGFR <60 ml/min per 1.73 m2 and/or proteinuria >300 mg/dl. Progressive decline in renal function was defined as an annual change rate of eGFR below the 10th percentile of the whole population. RESULTS: In the multivariate-adjusted model, we found that the risk of progressive decline in renal function increased consistently with the MetS score, with an odds ratio of 1.49 (95% CI, 1.28, 1.73) for those subjects>75th percentile compared with those <25th percentile. Additionally, a high MetS score was found to be associated with an increased risk of CKD, with a hazard ratio of 1.53 (95% CI, 1.33, 1.78) for subjects >75th percentile compared with those <25th percentile. CONCLUSIONS: Our findings suggested that the MetS score was associated with an increased risk of a progressive decline in renal function and was also a strong and independent risk factor for the development of CKD. These findings provide evidence of the potential clinical utility of the MetS score for assessing metabolic syndrome severity to detect the risk of decreased renal function and CKD.

Associations of longitudinal trajectories in body roundness index with mortality and cardiovascular outcomes: a cohort study.

BACKGROUND: The body roundness index (BRI) is a new anthropometric index that combines height and waist circumference to predict the percentages of total and regional fat. The longitudinal trajectories of BRI can reflect the long-term pattern of BRI changes; however, their effects on the incidence of cardiovascular disease (CVD) and mortality are poorly characterized. OBJECTIVES: Our aim was to identify BRI trajectories and to estimate their associations with mortality and incident CVD events. METHODS: This study included a total of 59,278 participants (mean age, 54.8 years) free of malignant tumors and CVD and with repeated measurements of BRI from 2006 to 2012. The BRI trajectories from 2006 to 2012 were identified using the latent mixture model. A Cox proportional hazards model was used to analyze the associations between BRI trajectories and the risk of CVD events and mortality. RESULTS: We grouped the BRI trajectories into 4 distinct groups during 2006-2012: low-stable (mean BRI = 2.7), moderate-stable (mean BRI = 3.7), moderate-high-stable (mean BRI = 4.7), and high-stable (mean BRI = 5.8). We identified 1928 CVD events and 2928 deaths during the follow-up. After adjustment for potential confounders, compared with the low-stable group, the HRs of CVD were 1.37 (95% CI: 1.19-1.58) for the moderate-stable group, 1.64 (95% CI: 1.40-1.91) for the moderate-high-stable group, and 2.03 (95% CI: 1.64-2.52) for the high-stable group. We observed similar associations for myocardial infarction and ischemic stroke. The association between BRI trajectories and CVD was more prominent in subjects aged <55 years. CONCLUSIONS: BRI trajectories were significantly associated with the risk of CVD, and the association was more evident in younger adults.

Transitions in metabolic health status over time and risk of heart failure: A prospective study.

AIMS: - Evidence for the effects of metabolically healthy obese (MHO) status on heart failure (HF) is limited and ignores the dynamic change of metabolic health and obesity phenotypes. We aimed to investigate the associations of metabolic health and its transition with HF across body mass index (BMI) and waist circumference (WC) categories. METHODS: - This prospective cohort study was conducted with 93,288 Chinese adults who were free of cardiovascular disease, cancer or HF at baseline (2006-2007). Metabolic health was defined as having no or only one abnormality in blood pressure, glucose, high-density lipoprotein cholesterol, or triglyceride levels. Participants were cross-classified at baseline by metabolic health and obesity (defined by BMI and WC criteria). Transitions in metabolic health status from 2006 to 2007 to 2010 to 2011 were considered. The hazard ratios (HRs) and 95% confidence intervals (CIs) for HF were assessed by Cox proportional hazards regression. RESULTS: - During a mean ± standard deviation follow-up of 9.7 ± 1.5 years, 1,628 participants developed HF. Individuals with MHO (HR: 1.78, 95% CI: 1.45, 2.19 for BMI criteria; HR: 1.51, 95% CI: 1.30, 1.76 for WC criteria) had higher risk of HF than those with metabolically healthy normal weight (MHNW). Individuals with initial MHO who shifted to metabolically unhealthy phenotype during follow-up had higher risk of HF compared with stable MHNW individuals (HR 3.12; 95% CI: 2.01, 4.85 for BMI categories; HR 1.98; 95% CI: 1.42, 2.77 for WC categories). Even stable MHO individuals were at an increased risk of HF compared with stable MHNW individuals (HR: 2.17; 95% CI: 1.39, 3.39 for BMI categories; HR: 1.33; 95% CI: 0.96, 1.85 for WC categories). CONCLUSIONS: - MHO phenotype is dynamic and its transition to metabolically unhealthy phenotype or even stable MHO is associated with increased risk of HF. Maintaining metabolic health may provide a clue for preventing HF.

Sequence-structure characterization of recombinant polypeptides derived from silk fibroin heavy chain.

The molecular conformation of a biomedical material plays a major role in the stability, bioactivity and controlled release of drugs. In order to identify the impact of fragments derived from Bombyx mori silk fibroin on their structures and to develop a new strategy for controlling drug release, we designed several hydrophobic-hydrophilic recombinants (GS16F1, GS16F4, and GS16F8), and investigated their molecular conformations and conformational changes induced by different storage temperatures and pH values. The results showed that the α-helix characteristic peaks were prominent in the fresh freeze-dried powder with increasing F1 repeats. During storage at 4 °C, 37 °C or 60 °C, the ß-turns (especially in GS16F8) and α-helixes turned into ß-sheets. The ß-sheet content in the polypeptides increased with increasing temperature and F1 repeats. Following induction by different pH values, their molecular conformations changed significantly, but not the same as that of powder storage. The content of ß-sheets was GS16F1 > GS16F4 > GS16F8 near the isoelectric point of each polypeptide. With increasing pH value, the ß-sheet content of GS16F1 decreased more slowly compared with GS16F4 and GS16F8. These results were satisfactory for structural regulation in the field of drug controlled release research.

Prenatal second-hand smoke exposure and newborn telomere length.

BACKGROUND: Cigarette smoking is associated with shorter telomere lengths in adults, but evidence on the effect of prenatal tobacco exposure is limited. We aimed to investigate the association between prenatal second-hand smoke exposure and newborn telomere length. METHODS: We recruited 762 mother-newborn pairs from Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) between November 2013 and March 2015. Information on second-hand smoke exposure was obtained via questionnaires. Relative telomere length was measured in DNA extracted from umbilical cord blood. We used linear regression to assess the associations between prenatal second-hand smoke exposure and newborn telomere length. RESULTS: In the fully adjusted model, prenatal second-hand smoke exposure was associated with 9.7% shorter newborn telomere length (percent difference: -9.7%; 95% confidence interval (CI): -15.0, -4.0). The estimate for boys was lower (percent difference: -10.9%; 95% CI: -18.6, -2.5) than that for girls (percent difference: -8.5%; 95% CI: -15.8, -0.5), but the interaction term between newborn sex and prenatal second-hand smoke was not significant (P = 0.751). CONCLUSIONS: This study demonstrated that prenatal second-hand smoke exposure may be a preventable risk factor for accelerated biological aging in the intrauterine stage, and further suggested possible sex differences in the susceptibility to prenatal second-hand smoke.

Prenatal aluminum exposure is associated with increased newborn mitochondrial DNA copy number.

Aluminum is a widely distributed metal that has been reported to have embryotoxicity and fetotoxicity in animal studies. However, there has been no study of the association between prenatal aluminum exposure and newborn mitochondrial DNA copy number (mtDNAcn). We aimed to investigate the effect of prenatal aluminum exposure on newborn mtDNAcn. A total of 762 mother-newborn pairs were recruited between November 2013 and March 2015 in Wuhan city, China. We measured maternal urinary aluminum concentrations at three trimesters of pregnancy. Relative mtDNAcn was measured in DNA extracted from umbilical cord blood samples. We used generalized estimating equations to assess the relationship between prenatal aluminum exposure and newborn mtDNAcn. The geometric means of creatinine corrected aluminum concentrations were 31.0 µg/g Cr (95% CI: 27.6, 34.7), 40.9 µg/g Cr (95% CI: 35.7, 46.8) and 58.4 µg/g Cr (95% CI: 51.2, 67.4) for the first, second and third trimesters, respectively. After adjustment for potential confounding factors, a doubling of maternal urinary aluminum concentrations during the second and third trimesters was related to 3.16% (95% CI: 0.88, 5.49) and 4.20% (95% CI: 1.64, 6.81) increases in newborn mtDNAcn, respectively, while the association between maternal urinary aluminum concentration during the first trimester and newborn mtDNAcn was not significant (percent difference: 0.70%, 95% CI: -2.25, 3.73). Prenatal aluminum exposure during the second and third trimesters was positively associated with newborn mtDNAcn. Further studies are essential to elucidate on the potential health consequences of newborn mtDNAcn.

Prenatal cadmium exposure is associated with shorter leukocyte telomere length in Chinese newborns.

BACKGROUND: Newborn telomere length (TL) is considered a potential marker for future disease and lifelong health, but few epidemiological studies have examined the determinants of TL in early life. The study aim was to investigate whether there is an association between prenatal cadmium exposure and relative cord blood TL in Chinese newborns. METHODS: Participants were 410 mother-newborn pairs drawn from a prospective birth cohort study conducted in Wuhan, China, between November 2013 and March 2015. Urine samples were collected from pregnant women during their period of institutional delivery. Urinary cadmium concentrations were measured by inductively coupled plasma mass spectrometry. The real-time quantitative polymerase chain reaction detection was used to measure relative TL using genomic DNA isolated from umbilical cord blood leukocytes. Multivariate linear regression models were used to estimate the effect of prenatal urinary cadmium concentration on relative cord blood TL. RESULTS: The geometric mean of maternal urinary cadmium concentration was 0.68 µg/g creatinine. In the multivariate-adjusted linear regression model, per doubling of maternal urinary cadmium concentration was associated with 6.83% (95% CI - 11.44%, - 1.97%; P = 0.006) shorter relative cord blood TL. Stratified analyses indicated that the inverse association between prenatal urinary cadmium and newborn relative TL was more pronounced among female infants and mothers < 29 years, while there were no significant effect modification according to infant sex (P for interaction = 0.907) and maternal age (P for interaction = 0.797). CONCLUSIONS: The findings indicated that increased maternal urinary cadmium was associated with shortened relative cord blood TL. The results provide more evidence of the negative effects of environmental cadmium exposure and suggest that accelerated aging or cadmium-related diseases may begin in early life.

Biosynthesis and Characterization of Recombinant Silk-Like Polypeptides Derived from the Heavy Chain of Silk Fibrion.

In order to investigate the impacts on the structure and biomedical function of typical fragments derived from repetitive and non-repetitive regions of the Bombyx mori silk fibroin heavy chain, several block combination genes (gs16f1, gs16f4, gs16f8, and gs16f12) were designed, cloned into a fusion protein expression vector tagged with glutathione S-transferase (GST), and expressed in Escherichia coli. Fusion proteins GST-GS16F1, GST-GS16F4, and GST-GS16F8 were purified by GST affinity chromatography, and single bands were identified by SDS-PAGE. Under optimal initial cell density, in ducer concentration and induction expression time, the yield of purified GST-GS16F1, GST-GS16F4, and GST-GS16F8 per liter of bacterial culture reached 79, 53, and 28 mg, respectively. Mass spectrometry revealed molecular weights for GST-GS16F1, GST-GS16F4, and GST-GS16F8 of 37.7, 50.0, and 65.7 kDa, respectively, consistent with the theoretical values of 37.4, 49.4, and 65.5 kDa. Similarly, measured values of pI were 5.35, 4.5, and 4.2 for the fusion proteins, consistent with predicted values of 5.34, 4.44, and 4.09. CD spectra showed the molecular conformation of GS16F1 was mainly ß-sheet structure, while more stable α-helix structure formed in GS16F4 and GS16F8.

Biosynthesis and characterization of a non-repetitive polypeptide derived from silk fibroin heavy chain.

Silk fibroin heavy chain is the major protein component of Bombyx mori silk fibroin and is composed of 12 repetitive and 11 non-repetitive regions, with the non-repetitive domain consisting of a hydrophilic polypeptide chain. In order to determine the biomedical function of the non-repetitive domain or potentially use it to modify hydrophobic biomaterials, high-purity isolation is necessary. Previously, we cloned and extended a gene motif (f(1)) encoding the non-repetitive domain. Here, this motif and its multimers are inserted into a glutathione S-transferase (GST)-tagged fusion-protein expression vector. Motif f(1) and multimers f(4) and f(8) were expressed in Escherichia coli BL21 cells following isopropyl ß-D-1-thiogalactopyranoside induction, purified by GST-affinity chromatography, and single bands of purified fusion proteins GST-F(1), GST-F(4), and GST-F(8), were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Target polypeptides F(1), F(4), and F(8), were cleaved clearly from the GST-fusion tag following thrombin digestion. Mass spectrometry results indicate that the molecular weights associated with fusion proteins GST-F(1), GST-F(4), and GST-F(8) are 31.5, 43.8, and 59.0kDa, respectively, and with the cleaved polypeptides F(1), F(4), and F(8) are 4.8, 16.8, and 32.8kDa, respectively. The F(1), F(4), and F(8) polypeptide chains are negatively charged with isoelectric points (pI) of 3.3, 3.2, and 3.0, respectively. The molecular weight and pI values of the polypeptide chains are consistent with the predicted values and the amino acid compositions similar to predicted sequences. FTIR and CD results show the molecular conformation of F(1) was mainly random coil, and more stable α-helix structure formed in longer molecular chain.