The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

High-Yield Synthesis of Lacto-N-Neotetraose from Glycerol and Glucose in Engineered Escherichia coli.

Lacto-N-neotetraose (LNnT) is a neutral human milk oligosaccharide with important biological functions. However, the low LNnT productivity and the incomplete conversion of the intermediate lacto-N-tetraose II (LNT II) currently limited the sustainable biosynthesis of LNnT. First, the LNnT biosynthetic module was integrated in Escherichia coli. Next, the LNnT export system was optimized to alleviate the inhibition of intracellular LNnT synthesis. Furthermore, by utilizing rate-limiting enzyme diagnosis, the expressions of LNnT synthesis pathway genes were finely regulated to further enhance the production yield of LNnT. Subsequently, a strategy of cofermentation using a glucose/glycerol (4:6, g/g) mixed feed was employed to regulate carbon flux distribution. Finally, by overexpressing key transferases, LNnT and LNT II titers reached 112.47 and 7.42 g/L, respectively, in a 5 L fermenter, and 107.4 and 2.08 g/L, respectively, in a 1000 L fermenter. These are the highest reported titers of LNnT to date, indicating its significant potential for industrial production.

Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population.

Background: The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening. Methods: A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell's C index change were used to validate the clinical importance of the thresholds. Results: Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49-2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001). Conclusion: On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.

Metabolic Engineering of Escherichia coli for High-Level Production of Lacto-N-neotetraose and Lacto-N-tetraose.

Lacto-N-neotetraose (LNnT) and lacto-N-tetraose (LNT) are important oligosaccharides found in breast milk and are commonly used as nutritional supplements in infant formula. We used metabolic engineering techniques to optimize the modified Escherichia coli BL21 star (DE3) strain for efficient synthesis of LNnT and LNT using ß-1,4-galactosyltransferase (HpgalT) from Helicobacter pylori and ß-1,3-galactosyltransferase (SewbdO) from Salmonella enterica subsp. salamae serovar, respectively. Further, we optimized the expression of three key genes, lgtA, galE, and HpgalT (SewbdO), to synthesize LNnT or LNT and deleted several genes (ugd, ushA, agp, wcaJ, otsA, and wcaC) to block competition in the UDP-galactose synthesis pathway. The optimized strain produced LNnT or LNT with a titer of 22.07 or 48.41 g/L, respectively, in a supplemented batch culture, producing 0.41 or 0.73 g/L/h, respectively. The strategies used in this study contribute to the development of cell factories for high-level LNnT and LNT and their derivatives.

Usefulness of the Duke Activity Status Index to Assess Exercise Capacity and Predict Risk Stratification in Patients with Pulmonary Arterial Hypertension.

Exercise capacity is an important component of risk assessment for pulmonary arterial hypertension (PAH). We investigated the association of the Duke Activity Status Index (DASI) with peak oxygen consumption (peakVO2) and explored whether the DASI can discriminate the high-risk individuals in patients with PAH, according to peakVO2 < 11 mL/min/kg. A total of 89 patients were evaluated using cardiopulmonary exercise testing (CPET) and DASI. The correlation between the DASI and peakVO2 was measured by univariate analysis, and a receiver operating characteristic (ROC) curve analysis was conducted. The DASI was correlated with peakVO2 in the univariate analysis. The ROC curve analysis revealed that the DASI had a discriminative value for identifying the individuals with a high risk in PAH patients (p < 0.001), with an area under ROC curve (AUC) of 0.79 (95% CI: 0.67-0.92). Similar results were observed in patients with PAH associated with congenital heart disease (CHD-PAH), (p = 0.001), with an AUC of 0.80 (95% CI: 0.658-0.947). Therefore, DASI reflects exercise capacity in patients with PAH and has good ability to discriminate patients with a low risk and a high risk, and it may be included in the risk assessment of PAH.

Temporal Trends and Differences in Sexuality among Depressed and Non-Depressed Adults in the United States.

This study aimed to examine temporal trends and differences in sexuality between depressed and non-depressed adults aged 18-59 in the United States from 2005 to 2016. A total of 21,437 people (5432 with depression) were enrolled in this cross-sectional study. From 2005-2008 to 2013-2016, the average age at first sexual intercourse decreased, while the proportion of normal frequency of sexual activity and heterosexual sexual orientation increased among all the participants. Some differences in sexuality were found between the depressed and non-depressed groups. The average age at first sexual intercourse (p < 0.001), the proportion of normal frequency of sexual activity (p < 0.001), and heterosexual sexual orientation (p < 0.001) were lower in depressed participants, and the differences did not change over time (pfor trend = 0.926 of average age at first sexual intercourse, pfor trend = 0.823 of normal frequency of sexual activity, pfor trend = 0.926 of heterosexual sexual orientation). Moreover, these differences were associated with marital status (pfor interaction < 0.001 by average age at first sexual intercourse), employment status (pfor interaction < 0.001 by average age at first sexual intercourse), education status (pfor interaction = 0.023 by heterosexual sexual orientation) and family income status (pfor interaction = 0.013 by average age at first sexual intercourse and pfor interaction = 0.017 by normal frequency of sexual activity). In conclusion, the study found that the age at first sexual intercourse decreased and the frequency of sexual intercourse increased in all the participants, and differences in sexuality between depressed and non-depressed participants were present; however, these differences had no further increase or decrease during the 12-year period. These differences were associated with marital status, employment status, education status, and family income status. These findings show differences in sexuality between depressed and non-depressed patients but are somewhat different from previous studies; the results may provide directions for future research and social work.

Multi-Path Optimization for Efficient Production of 2'-Fucosyllactose in an Engineered Escherichia coli C41 (DE3) Derivative.

2'-fucosyllactose (2'-FL), one of the simplest but most abundant oligosaccharides in human milk, has been demonstrated to have many positive benefits for the healthy development of newborns. However, the high-cost production and limited availability restrict its widespread use in infant nutrition and further research on its potential functions. In this study, on the basis of previous achievements, we developed a powerful cell factory by using a lacZ-mutant Escherichia coli C41 (DE3)ΔZ to ulteriorly increase 2'-FL production by feeding inexpensive glycerol. Initially, we co-expressed the genes for GDP-L-fucose biosynthesis and heterologous α-1,2-fucosyltransferase in C41(DE3)ΔZ through different plasmid-based expression combinations, functionally constructing a preferred route for 2'-FL biosynthesis. To further boost the carbon flux from GDP-L-fucose toward 2'-FL synthesis, deletion of chromosomal genes (wcaJ, nudD, and nudK) involved in the degradation of the precursors GDP-L-fucose and GDP-mannose were performed. Notably, the co-introduction of two heterologous positive regulators, RcsA and RcsB, was confirmed to be more conducive to GDP-L-fucose formation and thus 2'-FL production. Further a genomic integration of an individual copy of α-1,2-fucosyltransferase gene, as well as the preliminary optimization of fermentation conditions enabled the resulting engineered strain to achieve a high titer and yield. By collectively taking into account the intracellular lactose utilization, GDP-L-fucose availability, and fucosylation activity for 2'-FL production, ultimately a highest titer of 2'-FL in our optimized conditions reached 6.86 g/L with a yield of 0.92 mol/mol from lactose in the batch fermentation. Moreover, the feasibility of mass production was demonstrated in a 50-L fed-batch fermentation system in which a maximum titer of 66.80 g/L 2'-FL was achieved with a yield of 0.89 mol 2'-FL/mol lactose and a productivity of approximately 0.95 g/L/h 2'-FL. As a proof of concept, our preliminary 2'-FL production demonstrated a superior production performance, which will provide a promising candidate process for further industrial production.