DNA damage strength modulates a bimodal switch of p53 dynamics for cell-fate control

Background: The p53 pathway is differentially activated in response to distinct DNA damage, leading to alternative phenotypic outcomes in mammalian cells. Recent evidence suggests that p53 expression dynamics play an important role in the differential regulation of cell fate, but questions remain as to how p53 dynamics and the subsequent cellular response are modulated by variable DNA damage. Results: We identified a novel, bimodal switch of p53 dynamics modulated by DNA-damage strength that is crucial for cell-fate control. After low DNA damage, p53 underwent periodic pulsing and cells entered cell-cycle arrest. After high DNA damage, p53 underwent a strong monotonic increase and cells activated apoptosis. We found that the damage dose-dependent bimodal switch was due to differential Mdm2 upregulation, which controlled the alternative cell fates mainly by modulating the induction level and pro-apoptotic activities of p53. Conclusions: Our findings not only uncover a new mode of regulation for p53 dynamics and cell fate, but also suggest that p53 oscillation may function as a suppressor, maintaining a low level of p53 induction and pro-apoptotic activities so as to render cell-cycle arrest that allows damage repair.BiologySCI(E)10ARTICLEnull1

Study on the Dynamics of Differential Metabolites of Pu-erh Tea Fermented by Exogenous Added Bacteria

In order to explore the role of exogenous bacteria in the fermentation process of Pu-erh tea and its impact on tea quality, the present study aimed to explore the differences in metabolite changes during fermentation of Pu-erh tea treated with different bacterial strains. To achieve this, non-targeted metabolomics technology was employed, which was combined with multivariate statistical analysis and differential heat maps. The study analyzed the flavonoids, alkaloids, and terpenoids present in the tea samples. The H group was found to have a fruity and sweet aroma, a bright red soup color, and a strong and sweet taste. The A group had a strong floral and honey aroma, a bright red soup color, and a strong and sweet aftertaste. The R group had a fruity and milky aroma, a bright yellow soup color, and a strong but astringent and bitter taste. These differences in quality were found to be related to the levels of metabolites such as malvidin, genkwanin, catechins, caffeine, and lactucin. The study provided preliminary insights into the differences in metabolite content during the fermentation of Pu-erh tea with different bacterial strains, which can have varying effects on the taste, aroma, and soup color of the tea. The findings of this study could provide theoretical assistance for future Pu-erh tea fermentation

Isolation and extraction of glansreginin A from walnut meal and its effect on the proliferation of 3T3-L1 cells

Abstract Glansreginin A is an indicative component in walnut and is abundant in walnut meal. The aim of this study was to isolate and purify glansreginin A from the walnut meal, and to investigate the weight loss and lipid-lowering potential of glansreginin A by studying the effect of glansregin A on the proliferation of 3T3-L1 preadipocytes. Firstly, the response surface methodology was used to effectively improve the extraction yield of glansreginin A. The maximum extraction rate of glansreginin A was 0.363%, and the optimal extraction process conditions were determined. In addition, the lipid-lowering activity of glansreginin A was investigated by cell experiments. The results showed that glansreginin A could inhibit the proliferation of 3T3-L1 preadipocytes in a dose-dependent manner. And cell cycle of different groups of cells treated with glansreginin A was also measured using flow cytometry. The results showed most of the cells were blocked in G0/G1 phase and significantly decreased in S phase. These results suggest that glansreginin A could inhibit the proliferation of 3T3-L1 preadipocytes by causing cell cycle arrest. These findings provided a theoretical basis for the future research of glansreginin A and the development of slimming and fat-reducing foods

Expression and characterization of a protease-resistant β-d-fructofuranosidase BbFFase9 gene suitable for preparing invert sugars from soybean meal

A novel gene (BbFFase9), with an ORF of 1557 bp that encodes β-d-fructofuranosidase from Bifidobacteriaceae bacterium, was cloned and expressed in Escherichia coli. The recombinant protein (BbFFase9) was successfully purified and showed a single band with a molecular mass of 66.2 kDa. This was confirmed as a β-d-fructofuranosidase and exhibited a high specific activity of 209.2 U/mg. Although BbFFase9 was a soluble protein, it exhibited excellent tolerance to proteases such as pepsin, trypsin, acidic protease, neutral protease and Flavourzyme®, indicating its potential applicability in different fields. BbFFase9 exhibited typical invertase activity, and highly catalyzed the hydrolysis of the α1↔2β glycosidic linkage in molecules containing fructosyl moieties but with no detectable fructosyltransferase activity. It was optimally active at pH 6.5 and 50 °C and stable between pH 6.0 and 9.0 at a temperature of up to 45 °C for 30 min BbFFase9 could also effectively hydrolyze galacto-oligosaccharides, which are a flatulence factor in soybean meal, thus releasing new types of product such as melibiose and mannotriose, or degrading them into invert sugars, the sweeter fructose and glucose. This study is the first to report the application of this type of β-d-fructofuranosidase

Summary of Best Evidence for Self-Management of Patients with Motor Dysfunction after Stroke

Background Self-management meets the long-term rehabilitation needs of stroke patients and their families. However, there is a lack of relevant evidence, and there is no scientific and standardized self-management program in clinical practice. Objective To evaluate and summarize the best evidence of self-management in patients with motor dysfunction after stroke. Methods PubMed, Cochrane Library, Web of Science, Embase, CINAHL, CNKI, Wanfang Data, VIP, Chinese Biomedical Literature Database (CBM), American Heart Association/American Stroke Association (AHA/ASA), World Stroke Organization (WSO), Chinese Stroke Association (CSA), Guidelines International Network (GIN), Scottish Intercollegiate Guidelines Network (SIGN), National Guideline Clearinghouse (NGC), and Yimaitong were searched for relevant research evidence on self-management of patients with motor dysfunction after stroke from inception to July 2022, including guidelines, expert consensuses, systematic reviews, quasi-experimental studies, and randomized controlled studies. Two researchers independently evaluated the quality of the retrieved literature by using the 2017 version of the Appraisal of Guidelines for Research and Evaluation (AGREE Ⅱ) and the 2016 version of the literature evaluation criteria developed by the Joanna Briggs Institute (JBI) Evidence-based Health Care Center, extracted evidence and graded the quality of the evidence to summarize the best evidence of self-management in patients with motor dysfunction after stroke. Results A total of 36 studies were involved, including 9 guidelines, 4 expert consensuses, 5 systematic reviews, 5 quasi-experimental studies, and 13 randomized controlled studies, which were summarized in 6 aspects of organization and management, assessment, exercise instruction, health education, psychological support, monitoring and follow-up, and 34 pieces of best evidence. Conclusion The evidence of self-management in patients with motor dysfunction after stroke summarized in this study contains 6 aspects: organization and management, assessment, exercise instruction, health education, psychological support, monitoring and follow-up. Healthcare workers should select the best evidence based on the individual situation and needs of patients in the context of clinical practice, and provide personalized self-management interventions for patients, so as to improve their motor function and self-management ability, promoting the recovery of disease

A hybrid adaptive-prediction maximum power point tracking method for the smart city with massive photovoltaic

The partial shadow condition seriously affects the efficiency of the photovoltaic system in the modern city with dense built and other occlusions. From this, the characteristic curve of the photovoltage system shows multi-peak, which further increases the difficulty of getting photovoltaic systems to operate at maximum efficiency. As an efficient technique, the intelligent optimized maximum power point tracking method relies on initialization information and is difficult to balance the tracking performance. Therefore, a hybrid adaptive-prediction maximum power tracking method is proposed in this paper. Firstly, the neighborhood range of the maximum power points is located by the fuzzy predicted mechanism at the upper layer. Secondly, on the bottom layer, based on improving the Cuckoo search algorithm, the proposed method uses an interpolation function fitting curve to guide the particles to converge accurately on the bottom layer. At the same time, the output voltage of the system under an open loop is directly controlled by the duty cycle of the control signal, which improves the universality of the method. Finally, the simulation results show that the proposed method is superior to other advanced methods in tracking speed and with smaller power oscillations and comparable tracking accuracy, for which the proposed method is suitable for the city with complex environments and dense buildings

Antibacterial Regularity Mining Beneath the Systematic Activity Database of Lipopeptides Brevilaterins: An Instructive Activity Handbook for Its Food Application

Bacterial contamination is a primary threat to food safety. Therefore, the persistent development of natural antibacterial agents has become essential work. The present essay attempts to establish a systematic antibacterial activity database to instruct the food application of brevilaterins, promising antibacterial lipopeptides from Brevibacillus laterosporus S62-9. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were systematically collected from 43 species of standard bacteria and 140 strains of isolated bacteria (food spoilage bacteria and antibiotic-resistant bacteria) using a broth dilution method. The results showed that brevilaterins performed a broad-spectrum inhibitory (0.5~128 μg/mL) and bactericidal activity (1~256 μg/mL), especially efficient against Gram-positive bacteria and spoilage bacteria from grain products. Moreover, brevilaterins not only inhibit and kill multiple antibiotic-resistant bacteria but do not readily develop resistance, with a small specific value of MBC/MIC (1~8). Furthermore, brevilaterins would interact with negatively charged sodium dodecyl sulfate and bind amphipathic soybean phospholipid with an affinity constant of KD = 4.70 × 10−4 M. No significant activity difference was found between brevilaterin B and brevilaterin C. Collectively, this work contributed rich antibacterial data of brevilaterins and revealed the antibacterial regularity beneath these data, which can be used as an activity handbook to instruct their application in food safety

Conventional dendritic cell 2 links the genetic causal association from allergic asthma to COVID-19: a Mendelian randomization and transcriptomic study

Abstract Recent evidence suggests that allergic asthma (AA) decreases the risk of Coronavirus Disease 2019 (COVID-19). However, the reasons remain unclear. Here, we systematically explored data from GWAS (18 cohorts with 11,071,744 samples), bulk transcriptomes (3 cohorts with 601 samples), and single-cell transcriptomes (2 cohorts with 29 samples) to reveal the immune mechanisms that connect AA and COVID-19. Two-sample Mendelian randomization (MR) analysis identified a negative causal correlation from AA to COVID-19 hospitalization (OR = 0.968, 95% CI 0.940–0.997, P = 0.031). This correlation was bridged through white cell count. Furthermore, machine learning identified dendritic cells (DCs) as the most discriminative immunocytes in AA and COVID-19. Among five DC subtypes, only conventional dendritic cell 2 (cDC2) exhibited differential expression between AA/COVID-19 and controls (P < 0.05). Subsequently, energy metabolism, intercellular communication, cellular stemness and differentiation, and molecular docking analyses were performed. cDC2s exhibited more differentiation, increased numbers, and enhanced activation in AA exacerbation, while they showed less differentiation, reduced number, and enhanced activation in severe COVID-19. The capacity of cDC2 for differentiation and SARS-CoV-2 antigen presentation may be enhanced through ZBTB46, EXOC4, TLR1, and TNFSF4 gene mutations in AA. Taken together, cDC2 links the genetic causality from AA to COVID-19. Future strategies for COVID-19 prevention, intervention, and treatment could be stratified according to AA and guided with DC-based therapies. Graphical Abstrac

Flavonoids, gut microbiota, and host lipid metabolism

Abstract Flavonoids are widely distributed in nature and have a variety of beneficial biological effects, including antioxidant, anti‐inflammatory, and anti‐obesity effects. All of these are related to gut microbiota, and flavonoids also serve as a bridge between the host and gut microbiota. Flavonoids are commonly used to modify the composition of the gut microbiota by promoting or inhibiting specific microbial species within the gut, as well as modifying their metabolites. In turn, the gut microbiota extensively metabolizes flavonoids. Hence, this reciprocal relationship between flavonoids and the gut microbiota may play a crucial role in maintaining the balance and functionality of the metabolism system. In this review, we mainly highlighted the biological effects of antioxidant, anti‐inflammatory and antiobesity, and discussed the interaction between flavonoids, gut microbiota and lipid metabolism, and elaborated the potential mechanisms on host lipid metabolism