The effect of the interaction between intrinsic capacity and social support on the trajectories of activities of daily living in older adults.

OBJECTIVES: This study explored the effect of the interaction between intrinsic capacity and social support on the activities of daily living in the older adults. METHODS: A total of 3,124 older adults participated in the study. Data on the assessment of intrinsic capacity as well as activities of daily living (ADL) and social support were collected. The latent growth curve model (LGCM) was used to examine the effect of the interaction between social support and intrinsic capacity on the activities of daily living in the older adults. RESULTS: A total of 3,730 older adults were included at baseline, and 3,124 older adults completed the 4-year follow-up. The ADL score of the older adults showed a significant downward trend with time over 4 years (ß=-0.115, P<0.05). In the elderly population with high intrinsic capacity, the ADL of individuals with low levels of social participation decreased significantly over time (ß=-0.114, P=0.012). In the elderly group with low intrinsic capacity, the ADL of individuals with low levels of social participation (ß=-0.245, P=0.005) and high levels of life care (ß=-0.167, P=0.001) decreased significantly over time. CONCLUSION: This is the first longitudinal study to explore the effects of interactions among intrinsic capacity, social participation and family support on the trajectory of ADL in the older adults from the perspective of the life course. Social participation can effectively improve functional ability of older adults with low intrinsic capacity. Life care is beneficial for maintaining the functional ability of older adults with intact intrinsic capacity, but it accelerates the deterioration of the functional ability of older adults with low intrinsic capacity.

Developing and Validating a Nomogram for Non-Adherence to Inhaler Therapy Among Elderly Chronic Obstructive Pulmonary Disease Patients Based on the Social Ecological Model.

Purpose: This study aimed to identify the risk predictors of non-adherence to inhaler therapy and construct a nomogram prediction model for use in Chinese elderly patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: A cross-sectional study was conducted with 305 participants recruited from a tertiary care hospital in Anhui, China. Adherence was analyzed using the Test of Adherence to Inhalers. Potential predictive factors were incorporated based on the social ecological model, and data were collected through a questionnaire method. R version 4.3.3 was utilized to perform the least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis to identify risk factors and establish a nomogram prediction model. Results: The results of the multivariable analysis revealed that medication beliefs, illness perception, the COPD Assessment Test score, smoking status, and education level were significant risk factors for non-adherence to inhaler therapy in elderly COPD patients (all P < 0.05). The nomogram prediction model for non-adherence to inhaler therapy in elderly COPD patients demonstrated a good discriminative ability, with an area under the receiver operating characteristic curve of 0.912. The C-index was 0.922 (95% CI: 0.879 to 0.965), and the Brier value was 0.070, indicating good consistency and calibration. Decision curve analysis indicated that the use of the nomogram would be more beneficial in clinical practice when the threshold probability of non-adherence exceeds 17%. Conclusion: This study identified predictive factors regarding non-adherence among elderly patients with COPD and constructed a predictive nomogram. By utilizing the nomogram model healthcare professionals could swiftly calculate and comprehend the non-compliance level of COPD patients, thus guiding the development of personalized interventions in clinical practice.

A study on the reasonable dietary trajectory of elderly people in the community and its correlation with body mass index.

Objective: To explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits. Methods: The data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community. Results: The LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the "persistently unreasonable diet group" (p < 0.05). The logistic regression results showed that the "continuous reasonable diet group" and the "dietary behavior improvement group" were significantly correlated with the development of obesity to a normal BMI. Conclusion: The dietary behavior of the elderly was significantly correlated with BMI value, and improving the reasonable dietary behavior of the elderly could reduce the high BMI to the normal range, but could not restore the low BMI to the normal range, indicating that reasonable dietary behavior is an important measure to prevent and improve overweight or obesity in the elderly. There is significant heterogeneity in the dietary behavior of the elderly, and community medical staff should identify the risk factors of various dietary behaviors of other groups as soon as possible, and provide corresponding intervention strategies to help them change their poor dietary behaviors and improve their nutritional status.

Reducing Cellular Autolysis of Bacillus subtilis to Improve Keratinase Production.

Bacillus subtilis has been shown to be an excellent expression host for keratinases due to its powerful secretion system. However, cellular autolysis limits its production capacity. Here, we selected seven genes with significantly upregulated transcript levels from 15 genes associated with cellular autolysis as knockout targets by qRT-PCR and constructed a total of 127 strains to reduce cellular autolysis. Among them, the biomass of B. subtilis BSΔXLPC-ker deficient in xpf, lytC, pcfA, and cwlC increased by 57%. This was confirmed by cell staining, green fluorescent protein imaging, and extracellular nucleic acid leakage assay. Keratinase activity was increased by 1.46-fold in the 5 L fermenter. In addition, the activities of nattokinase and subtilisin E were also increased by 1.50-fold and 1.43-fold, respectively, in the modified chassis cells, which further confirms the generalizability of the strategy. Thus, reducing cellular autolysis to increase the ability of B. subtilis to produce subtilisins is promising.

Fusion of Substrate-Binding Domains Enhances the Catalytic Capacity of Keratinases and Promotes Enzymatic Conversion of Feather Waste.

The unique role of keratinases in keratin hydrolysis has garnered huge interest in the recovery of feather waste. However, owing to the high hydrophobicity of feather keratins, the catalytic capacity of keratinases for hydrolyzing feathers is typically low. In this study, we aimed to improve the keratinase feather hydrolysis efficiency by fusing a substrate-binding domain into the enzyme. We screened several carbohydrate-binding modules (CBMs) and linking peptides. We selected the most promising candidates to construct, clone, and express a fusion keratinase enzyme KerZ1/CBM-L8 with a feather hydrolysis efficiency of 7.8 × 10-8 g/U. Compared with those of KerZ1, KerZ1/CBM-L8 has a feather hydrolysis efficiency that is 2.71 times higher, a kcat value that is 179% higher, which translates to higher catalytic efficiency, and Km and binding constant (K) values that are lower, which indicate a higher KerZ1/CBM-L8-keratin binding affinity. Moreover, the number of binding sites to the substrate (N), determined using isothermal titration calorimetry, was 24.1 times higher than that of KerZ1. Thus, the fusion of the substrate-binding domain improved the binding ability of the keratinase enzyme to the hydrophobic substrate, which improved its feather hydrolysis efficiency. Therefore, using the fusion keratinase would significantly improve the recovery of feather waste.

Engineering flexible loops to enhance thermal stability of keratinase for efficient keratin degradation.

Keratinase-catalyzed degradation of keratin waste has been shown to be a promising recycling method. Although the recombinant KerZ1 derived from Bacillus subtilis has shown the highest activity among the keratinases reported so far, the low thermal stability caused by the unstable flexible loops limited its keratin-degrading ability. To this end, the flexible loops of KerZ1 were engineered to be more hydrophobic and rigid through B-factor calculations, molecular dynamics simulations, and ß-turn redesign. We developed several highly thermostable keratinase variants and showed enhanced keratin degradation activity. In particular, the loop regions of the variants KerZ1A128D/L240N, KerZ1T77E/L240N and KerZ1T77C/A128D were designed to be more stable, with Tm values increased by 8 °C, 6 °C and 5 °C, and corresponding t1/2 increased by 2.3, 3.3 and 5.0 times. The keratin degradation activity of the variant KerZ1T77C/A128D at 60 °C was enhanced by 46 % compared with KerZ1WT. The strategy of this research and the obtained keratinase variants will be a significant improvement in the complete degradation of keratin.

Improved acid-stress tolerance of Lactococcus lactis NZ9000 and Escherichia coli BL21 by overexpression of the anti-acid component recT.

Acid accumulation caused by carbon metabolism severely affects the fermentation performance of microbial cells. Here, different sources of the recT gene involved in homologous recombination were functionally overexpressed in Lactococcus lactis NZ9000 and Escherichia coli BL21, and their acid-stress tolerances were investigated. Our results showed that L. lactis NZ9000 (ERecT and LRecT) strains showed 1.4- and 10.4-fold higher survival rates against lactic acid (pH 4.0), respectively, and that E. coli BL21 (ERecT) showed 16.7- and 9.4-fold higher survival rates than the control strain against lactic acid (pH 3.8) for 40 and 60 min, respectively. Additionally, we found that recT overexpression in L. lactis NZ9000 improved their growth under acid-stress conditions, as well as increased salt- and ethanol-stress tolerance and intracellular ATP concentrations in L. lactis NZ9000. These findings demonstrated the efficacy of recT overexpression for enhancing acid-stress tolerance and provided a promising strategy for insertion of anti-acid components in different hosts.

Evolutionary engineering of industrial microorganisms-strategies and applications.

Microbial cells have been widely used in the industry to obtain various biochemical products, and evolutionary engineering is a common method in biological research to improve their traits, such as high environmental tolerance and improvement of product yield. To obtain better integrate functions of microbial cells, evolutionary engineering combined with other biotechnologies have attracted more attention in recent years. Classical laboratory evolution has been proven effective to letting more beneficial mutations occur in different genes but also has some inherent limitations such as a long evolutionary period and uncontrolled mutation frequencies. However, recent studies showed that some new strategies may gradually overcome these limitations. In this review, we summarize the evolutionary strategies commonly used in industrial microorganisms and discuss the combination of evolutionary engineering with other biotechnologies such as systems biology and inverse metabolic engineering. Finally, we prospect the importance and application prospect of evolutionary engineering as a powerful tool especially in optimization of industrial microbial cell factories.

[Effect of xiaoke granule on blood glucose, urinary protein and glomerular morphology in rats with diabetic nephropathy].

OBJECTIVE: To observe the changes of blood glucose, urinary protein and renal glomerular morphology in rats with diabetic nephropathy, and the effect of xiaoke granule (XKG) on them. METHODS: The diabetic nephropathy model was established by 3/4 nephrectomy and once intraperitoneal injection of streptozotocin (STZ). The experimental rats were divided into the model group, the XKG group, the positive control group and the sham operation group. Blood was taken from rat's caudal vein to test the fasting blood glucose (FBG) once every week after STZ injection and at the same time, urinary protein in 24 hrs (UP/24h) was investigated. All the rats were sacrificed 2, 6 weeks after STZ injection and morphological examination on their kidney was performed. RESULTS: Six weeks after STZ injection, glomerular sclerosis in various degrees was seen in the model group, but the pathological change was significantly milder in the treated groups. FBG in the model group was higher than that in the sham operation group at all time points respectively (P<0.05), while in the XKG group and the positive control group, the change was improved significantly. UP/24h in the model group was higher than that in the sham operation group at all time points respectively, and that in the XKG group at 1, 2 and 3 weeks after STZ injection was significantly lower than that in the model group. FBG and UP/24h showed a positive correlation. CONCLUSION: A rat model of diabetic nephropathy was duplicated successfully. The elevated blood glucose level in diabetic nephropathy model could induce proteinuria. One of the routes of treatment of diabetic nephropathy by XKG is to reduce the blood glucose, eliminate the proteinuria, and thus to improve the pathological change in renal glomeruli.