Abstract This study was initiated to improve E. coli succinate production by engineering the E. coli global transcription factor, Cra (catabolite repressor/activator). Random mutagenesis libraries were generated through error-prone PCR of cra . After re-screening and mutation site integration, the best mutant strain was Tang1541, which provided a final succinate concentration of 79.8 ± 3.1 g/L: i.e., 22.8% greater than that obtained using an empty vector control. The genes and enzymes involved in phosphoenolpyruvate (PEP) carboxylation and the glyoxylate pathway were activated, either directly or indirectly, through the mutation of Cra. The parameters for interaction of Cra and DNA indicated that the Cra mutant was bound to aceBAK , thereby activating the genes involved in glyoxylate pathway and further improving succinate production even in the presence of its effector fructose-1,6-bisphosphate (FBP). It suggested that some of the negative effect of FBP on Cra might have been counteracted through the enhanced binding affinity of the Cra mutant for FBP or the change of Cra structure. This work provides useful information about understanding the transcriptional regulation of succinate biosynthesis.
Populations of organisms that are chronically exposed to high levels of chemical contaminants may not suffer the same sublethal or lethal effects as naive populations, a phenomenon called resistance. Atlantic tomcod (Microgadus tomcod) from the Hudson River, New York, are exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs) and bioaccumulate polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). They have developed resistance to PCBs and PCDDs but not to PAHs. Resistance is largely heritable and manifests at early-life-stage toxic end points and in inducibility of cytochrome P4501A (CYP1A) mRNA expression. Because CYP1A induction is activated by the aryl hydrocarbon receptor (AHR) pathway, as are most toxic responses to these compounds, we sought to determine the geographic extent of resistance to CYP1A mRNA induction by PCBs in the Hudson River tomcod population. Samples of young-of-the-year tomcod were collected from seven locales in the Hudson River, extending from the Battery at river mile 1 (RM 1) to RM 90, and from the Miramichi River, New Brunswick, Canada. Laboratory-reared offspring of tomcod adults from Newark Bay, in the western portion of the Hudson River estuary, were also used in this study. Fish were partially depurated in clean water and intraperitoneally injected with 10 ppm coplanar PCB-77, 10 ppm benzo[a]pyrene (BaP), or corn oil vehicle, and levels of CYP1A mRNA were determined. CYP1A was significantly inducible by treatment with BaP in tomcod from the Miramichi River, from laboratory-spawned offspring of Newark Bay origin, and from all Hudson River sites spanning 90 miles of river. In contrast, only tomcod from the Miramichi River displayed significantly induced CYP1A mRNA expression when treated with PCB-77. Our results suggest that the population of tomcod from throughout the Hudson River estuary has developed resistance to CYP1A inducibility and probably other toxicities mediated by the AHR pathway. Tomcod from the Hudson River may represent the most geographically expansive population of vertebrates with resistance to chemical pollutants that has been characterized.
Osteoblasts have the capacity to differentiate into several different cell types, including adipocyte, chondrocyte, and muscle lineages. Therefore, osteoblast can be potentially applied in the treatment of bone diseases. The factors controlling osteoblast differentiation is complex. Recently, it has been reported that some natural products regulate the differentiation in osteoblasts and promote bone formation. Based on these findings, this study demonstrated that Lycium barbarum polysaccharides (LBP) could promote proliferation of osteoblast MC3T3-E1 cells through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Besides, expression of key proteins correlated with cellular proliferation such as proliferating cell nuclear antigen (PCNA) and Ki67 was enhanced in the presence of LBP. We also detected the increased expression of bone-specific matrix proteins such as morphogenetic protein 2 (BMP2), bone Gla protein (BGP), osteopontin (OPN), and α-1 type-I collagen (COL1A1) when treated with LBP. This process was mediated by some signals, such as smad1, smad8, Runt-related transcription factor 2 (RUNX2), and Osterix. Furthermore, RUNX2 silencing inhibited osteoblast differentiation by decreasing expression of bone-specific matrix proteins. Collectively, we proposed a previously unidentified function of LBP in osteoblast differentiation, suggesting its potential clinical role in bone disease treatment.
Since the outbreak of coronavirus disease 2019 (COVID-19) in late 2019, it has evolved into a global pandemic that has become a substantial public health concern. COVID-19 is still causing a large number of deaths in several countries around the world because of the lack of effective treatment.To systematically compare the outcomes of COVID-19 patients treated with integrated Chinese with western (ICW) medicine versus western medicine (WM) alone by pooling the data of published literature, and to determine if ICW treatment of COVID-19 patients has better clinical outcomes.We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China Clinical Trial Registry, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang databases using keywords related to COVID-19, traditional Chinese medicine (TCM) and treatment effect. The search deadline was until 10 February 2021. All randomised controlled (RC) and non-randomised controlled (NRC) clinical trials of the ICW or WM treatment of COVID-19 patients were included. We analysed the effective rate, cure rate, exacerbation rate, turning negative rate of viral nucleic acid, remission rate and remission time of symptoms such as fever, cough, feebleness and chest computed tomography (CT) and the number of white blood cells (WBCs) and lymphocytes (LYM) of the COVID-19 patients. For qualitative and quantitative data, the ratio risk (RR) and weighted mean difference (WMD) were used as the indexes of the statistical analysis, respectively. RevMan 5.4 was used to perform meta-analyses and forest plots with the fixed-effects and random-effects models. Cochrane risk of bias tool (RoB 2.0) was used to assess the risk of bias in the included RC trials, whereas risk of bias in non-randomised studies of interventions was used to assess the risk of bias in NRC trials.This research includes 16 studies with 1645 valid confirmed COVID-19 patients, among which 895 patients of the experimental group received ICW treatment whereas 750 patients of the control group received WM treatment. The outcomes were assessed in three aspects, that is, overall indicator, symptoms indicator and blood indicator, respectively, and the results showed that the ICW group had better treatment outcomes compared with the WM. Among the overall indicators, the ICW group displayed a higher effective rate (RR = 1.24, 95% confidence interval (CI): 1.16-1.33), clinical cure rate (RR = 1.27, 95% CI: 1.03-1.56) and lower exacerbation rate (RR = 0.36, 95% CI: 0.25-0.52), but no statistical difference was observed in the turning negative rate of viral nucleic acid (RR = 1.20, 95% CI: 0.78-1.85). Among the symptom indicators, the ICW group had a higher fever remission rate (RR = 1.24, 95% CI: 1.09-1.42), less fever remission time (WMD = -1.49, 95% CI: -1.85 to -1.12), a higher cough remission rate (RR = 1.38, 95% CI: 1.10-1.73) and a feebleness remission rate (RR = 1.45, 95% CI: 1.18-1.77), less cough remission time (WMD = -1.61, 95% CI: -2.35 to -0.87) and feebleness remission time (WMD = -1.50, 95% CI: -2.38 to -0.61) and better improvement in chest CT (RR = 1.19, 95% CI: 1.11-1.28). For blood indicator, the number of WBCs in the blood of patients of ICW group rebounded significantly (WMD = 0.35, 95% CI: 0.16-0.54), and the recovery of LYM in the blood was more obvious (WMD = 0.23, 95% CI: 0.06-0.40).The results of this study show that the outcomes in COVID-19 patients treated by the ICW is better than those treated by the WM treatment alone, suggesting that WM and TCM can be complementary in the treatment of COVID-19.
This study aimed to evaluate the associations between fruit and vegetable (FV) intake and the risk of prediabetes or type 2 diabetes (T2D). It is a cross-sectional study that involved 6802 participants aged 18–65 years. Dietary intake and other variables were assessed by questionnaires. The prevalence of prediabetes and T2D was ascertained by self-report and analyses of fasting blood samples. In the multiple logistic regression models, FV intake was negatively associated the risk of T2D in women (OR = 0.45, 95% CI: 0.28, 0.71), whereas no such association was observed in men (OR = 0.98, 95% CI: 0.65, 1.47). Furthermore, FV consumption was inversely associated with prediabetes risk in men and women. Results suggested that higher intake of FV was associated with a decreased risk of T2D or prediabetes in Chinese women and a reduced risk of prediabetes in men only.
Hypertension is frequently studied in surveys; however, prehypertension, a new blood pressure status between normotension and hypertension, is rarely reported.All data were derived from the China Health and Nutrition Survey (CHNS) and were analysed by logistic regression for correlation.The prehypertension prevalence was 27.4%, with a hypertension rate of 36.9%. The awareness, treatment, and uncontrolled rates among all hypertension participates were 19.8%, 83.6%, and 55.0%, respectively. The epidemic rate of hypertension increased with increasing age (p < 0.001), and prehypertension appeared to have an epidemic peak in the age group of 38-57 years (p < 0.001). In general, the incidence of hypertension in urban participants was higher than in rural subjects (p < 0.001), and prehypertension in urban subjects was lower than that in rural subjects (p < 0.001). According to the results of logistic regression, hypertension and prehypertension were associated with age, gender, location, body mass index (BMI), body fat rate (BFR), waist circumference (WC), education, and the intake of energy-yielding nutrients<0.05).The current study reveals a high epidemic rate of hypertension and prehypertension in Central China. These results indicate the urgent need to develop strategies to improve the prevention of hypertension and prehypertension in Central China.
Some articles have examined perfluorooctanoic acid (PFOA) exposure in early life in relation to risk of childhood adiposity. Nevertheless, the results from epidemiological studies exploring the associations remain inconsistent and contradictory. We thus conducted an analysis of data currently available to examine the association between PFOA exposure in early life and risk of childhood adiposity. The PubMed, EMBASE, and Web of Science databases were searched to identify studies that examined the impact of PFOA exposure in early life on childhood adiposity. A random-effects meta-analysis model was used to pool the statistical estimates. We identified ten prospective cohort studies comprising 6076 participants with PFOA exposure. The overall effect size (relative risk or odds ratio) for childhood overweight was 1.25 (95% confidence interval (CI): 1.04, 1.50; I2 = 40.5%). In addition, exposure to PFOA in early life increased the z-score of childhood body mass index (β = 0.10, 95% CI: 0.03, 0.17; I2 = 27.9%). Accordingly, exposure to PFOA in early life is associated with an increased risk for childhood adiposity. Further research is needed to verify these findings and to shed light on the molecular mechanism of PFOA in adiposity.
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