The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.

Background: Mild cognitive impairment (MCI) is a critical stage of dementia. Previous reviews have suggested that physical exercise combined with non-invasive brain stimulation is more beneficial for improving cognitive function. However, no targeted studies have confirmed the effect of Tai Chi combined with transcranial direct current stimulation (tDCS) on the improvement of cognitive function in patients with MCI. Thus, this randomized trial was conducted to assess the effect of Tai Chi combined with tDCS on the cognitive performance of patients with MCI.Methods: From April 2018 to February 2020, a randomized, single-blind clinical trial was conducted, involving 180 participants with MCI who were divided into four intervention groups: Tai Chi combined with tDCS (TCT), Tai Chi combined with sham tDCS (TCS), walking combined with tDCS (WAT), and walking combined with sham tDCS (WAS). All participants were assessed at baseline and 12 weeks for global cognitive function, memory, attention, and executive function.Results: At baseline, there were no significant differences in age, gender, education duration, body mass index, or the Baker Depression Inventory among the four groups (P ≥ 0.05). After 12 weeks of intervention, the TCT group showed greater improvements in MOCA scores, memory quotient scores, and digit-symbol coding task reaction time compared to the TCS, WAS, and WAT groups (P < 0.05). The TCT group also had a shorter Stroop test color reaction time compared to the WAS and WAT groups (P < 0.05), a higher increase in Auditory Verbal Learning Test-immediate recall than the TCS and WAT groups (P < 0.05), a shorter visual reaction time than the TCS group (P < 0.05), and a shorter sustained attention time compared to the WAT group (P < 0.05).Conclusion: Tai Chi combined with tDCS effectively improves global cognitive performance, memory, execution function, and attention in patients with MCI. These findings suggest the potential clinical use of Tai Chi combined with tDCS as a physical exercise combined with a non-invasive brain stimulation intervention to improve cognitive function in older adults with MCI.Clinical trial registration: ChiCTR1800015629.

Background: Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. Methods: After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. Results: The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia). Conclusions: The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).

Severe pneumonia (SP) is a respiratory tract disease that seriously threatens human health. The herpesvirus detected in patients, especially with severe and immunodeficient diseases, is gradually attracting the attention of clinical doctors. However, little is known about the effect of herpesvirus on the prognosis of SP patients and the pulmonary microbial community. Here, we retrospectively analyzed respiratory samples from 45 SP patients detected by metagenomic next-generation sequencing (mNGS). A total of five types of herpesviruses were detected, with Human alphaherpesvirus 1 (HHV-1) in 19 patients, Human betaherpesvirus 5 (CMV) in 7 patients, Human betaherpesvirus 7 (HHV-7) in 6 patients, Human alphaherpesvirus 2 (HHV-2) in 5 patients, and Human gammaherpesvirus 4 (EBV) in 4 patients. Further analysis showed that the mortality of the herpesvirus-positive group was significantly higher than that of the negative group. The results also showed that HHV-1 was significantly associated with the prognosis of SP patients, while the other herpesviruses did not have a significant difference in patient mortality. A comparison of the microbial community characteristics of SP patients showed a significant difference in beta-diversity between herpesvirus-positive and negative groups. Species difference analysis showed that the herpesvirus-positive group was related to more conditional pathogens, such as Pneumocystis jirovecii and Burkholderia cepacia. In summary, our results suggest that the presence of herpesvirus is associated with the mortality of SP patients. Furthermore, enrichment of conditional pathogens in the respiratory tract of herpesvirus-positive SP patients may be a potential reason for the increased mortality.

Although epidemiological evidence has established a link between physical exercise and reduced risk and recurrence of multiple cancers, the association between physical exercise and cancer risk varies depending on the cancer site. Therefore, there is an urgent need to explore the molecular mechanisms underlying the antitumor effects of exercise to identify which types of cancers can benefit the most from physical exercise. Recent studies have shown that amino acids and exercise-induced lactate can be used by Carnosine Dipeptidase 2 (CNDP2) to synthesize lactoyl amino acids (Lac-AAs), which are then immediately secreted. Thus, we propose that lactate can deplete intracellular amino acids in a CNDP2-dependent manner, thereby exerting antitumor effects. Further bioinformatics analysis revealed that clear cell renal cell carcinoma (ccRCC) has the highest CNDP2 expression level among the 33 types of cancer tissues. Therefore, we focused on the inhibitory effects of lactate in this type of cancer and indeed confirmed its inhibitory roles in both cell and animal models. This study not only provides compelling evidence for the anti-cancer effects of physical exercise in ccRCC, but also provides novel insights into the biological role of lactate in the tumor microenvironment and offers potential therapeutic opportunities for mechanism-based treatment of ccRCC.