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Background: Cardiovascular illness and gallstones are closely related. Our goal was to determine whether gallstones and the updated LE8 score, which measures cardiovascular health among US adults, are related. Methods: 3,570 adults participated in the 2017–2018 National Health and Nutrition Examination Survey, which provided the data for our study. Based on the criterion provided by the American Association for Cardiovascular Health (AHA), LE8 score (range 0–100) was calculated and classified as low (0–49), moderate (50–79), and high (80–100) cardiovascular health. Gallstones were derived from the questionnaire. Multivariate logistic modeling explored the independent relationship between LE8 score and gallstones. Results: There was a negative correlation between LE8 score and gallstones. Specifically, the odds of gallstones dropped by 15% for each 10-unit increase in LE8 score (OR = 0.85; 95% CI, 0.77–0.94). Smooth curve fitting detected a saturation effect between LE8 score and gallstones, with a minimum threshold of 66.25 points associated with both. There was a noticeably stronger inverse relationship between gallstones and LE8 score in those under 60 years of age and not taking antihypertensive or lipid-lowering drugs. Conclusions: Lower LE8 scores may be a potential risk factor for the development of gallstones and could also be a target for risk assessment and intervention. [ABSTRACT FROM AUTHOR]

Objective: To establish experimental models of radical hysterectomy based on Querleu-Morrow classification, and clarify the quantitative evaluation of pelvic neural injuries and acute voiding changes postoperatively. Methods: Female Sprague Dawley rats were randomized and received sham operation, type A, B1, C1 and C2 radical hysterectomies (as the injury gradually increased), respectively. The excised specimens were collected for hematoxylin and eosin staining and Pgp9.5 (pan-neuronal marker) immunohistochemistry to evaluate the facial and neural resection of paracervix. At 21 days after operation, 5 rats in each group were used for urine spot test, awake cystometry and leak point pressure test, and the other 5 ones were used for hematoxylin and eosin staining of bladder and pelvic neural plane, and Masson's trichrome staining of bladder. Results: Paracervical Pgp9.5 immunohistochemistry revealed that the resected neural area in C2 group was significantly larger than that in type A, B1, and C1 groups. Compared with type A and B1 groups, the excised paracervical facial area was significant higher in type C1 and C2 groups. The occurrence of urinary retention was 0%, 10%, 40% and 100% in type A, B1, C1 and C2 groups, respectively, which was further confirmed by average residual volume. The incidence of neurogenic bladder and its severity gradually increased from type A to type C2 groups, consistent with the findings of leakage point pressure, bladder size, bladder weight, pathological changes and collagen deposition. Neuropathological evaluation revealed neural injuries involved the main components of pelvic neural plane. Conclusion: The novel rat models of radical hysterectomy based on Querleu-Morrow classification revealed the structural and functional changes of voiding after operation, which reflected the situation in humans. [ABSTRACT FROM AUTHOR]

Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1) and metazoan (type 2) opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs), of which metazoan type 2 opsins are a light-specific sub-clade.

Fine particulate matter (PM2.5) and near-surface ozone (O3) are the main atmospheric pollutants in China. Long-term exposure to high ozone concentrations adversely affects human health. It is of great significance to systematically analyze the spatiotemporal evolution mechanism and health effects of ozone pollution. Based on the ozone data of 91 monitoring stations in the Central Plains Urban Agglomeration from 2017 to 2020, the research used Kriging method and spatial autocorrelation analysis to investigate the spatiotemporal variations of ozone concentration. Additionally, the study assessed the health effects of ozone on the population using the population exposure risk model and exposure-response relationship model. The results indicated that: (1) The number of premature deaths caused by ozone pollution in the warm season were 37,053 at 95% confidence interval (95% CI: 28,190–45,930) in 2017, 37,685 (95% CI: 28,669–46,713) in 2018, and 37,655 (95% CI: 28,647–46,676) in 2019. (2) The ozone concentration of the Central Plains urban agglomeration showed a decreasing trend throughout the year and during the warm season from 2017 to 2020, there are two peaks monthly, one is June, and the other is September. (3) In the warm season, the high-risk areas of population exposure to ozone in the Central Plains Urban Agglomeration were mainly concentrated in urban areas. In general, the population exposure risk of the south is lower than that of the north. The number of premature deaths attributed to ozone concentration during the warm season has decreased, but some southern cities such as Xinyang and Zhumadian have also seen an increase in premature deaths. China has achieved significant results in air pollution control, but in areas with high ozone concentrations and high population density, the health burden caused by air pollution remains heavy, and stricter air pollution control policies need to be implemented. [ABSTRACT FROM AUTHOR]

In bacteriorhodopsin, the order of molecular events that control the cytoplasmic or extracellular accessibility of the Schiff bases (SB) are not well understood. We use molecular dynamics simulations to study a process involved in the second accessibility switch of SB that occurs after its reprotonation in the N intermediate of the photocycle. We find that once protonated, the SB C15 = NZ bond switches from a cytoplasmic facing (13-cis, 15-anti) configuration to an extracellular facing (13-cis, 15-syn) configuration on the pico to nanosecond timescale. Significantly, rotation about the retinal's C13 = C14 double bond is not observed. The dynamics of the isomeric state transitions of the protonated SB are strongly influenced by the surrounding charges and dielectric effects of other buried ions, particularly D96 and D212. Our simulations indicate that the thermal isomerization of retinal from 13-cis back to all-trans likely occurs independently from and after the SB C15 = NZ rotation in the N-to-O transition.

Chronic low-grade inflammation is regarded to an important signature of atherosclerosis (AS). Macrophage (Mψ) and related polarization have been demonstrated to play a crucial role in the occurrence and development of AS inflammation. Butyrate, a bioactive molecule produced by the intestinal flora, has been increasingly demonstrated to exhibit a vital role for regulating the inflammation in chronic metabolic diseases. However, the effectiveness and multiple anti-inflammation mechanisms of butyrate on AS still need to be further understood. ApoE−/− mice fed with high-fat diet as AS model were administered with sodium butyrate (NaB) for 14 weeks of treatment. Our results showed that the atherosclerotic lesion in the AS group was dramatically reduced after NaB intervention. Moreover, deteriorated routine parameters of AS including body weights (BWs), low-density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC) were significantly reversed by NaB administration. Abnormal elevated plasma and aorta pro-inflammatory indicators including interleukin (IL)-1β, IL-6, IL-17A, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), as well as reduced anti-inflammatory IL-10 in plasma were respectively rectified after NaB administration. Consistently, accumulated Mψ and associated imbalance of polarization in the arota were attenuated with NaB treatment. Importantly, we demonstrated that the suppression of Mψ and associated polarization of NaB was dependent on binding G-protein coupled receptor (GPR) and inhibiting histone deacetylase HDAC3. Moreover, we found that intestinal butyrate-producing bacteria, anti-inflammatory bacteria and intestinal tight junction protein zonula occludens-1 (ZO)-1 may contribute to this effectiveness. Intriguingly, according to transcriptome sequencing of atherosclerotic aorta, 29 elevated and 24 reduced miRNAs were found after NaB treatment, especially miR-7a-5p, suggesting that non-coding RNA may possess a potential role in the protection of NaB against AS. Correlation analysis showed that there were close complicated interactions among gut microbiota, inflammation and differential miRNAs. Collectively, this study revealed that dietary NaB may ameliorate atherosclerotic inflammation by regulating Mψ polarization via GPR43/HDAC-miRNAs axis in ApoE−/− mice. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is closely associated with chronic low-grade inflammation and gut dysbiosis. Metformin (MET) presents pleiotropic benefits in the control of chronic metabolic diseases, but the impacts of MET intervention on gut microbiota and inflammation in AS remain largely unclear. In this study, ApoE-/- mice with a high-fat diet (HFD) were adopted to assess the MET treatment. After 12 weeks of MET intervention (100mg·kg-1·d-1), relevant indications were investigated. As indicated by the pathological measurements, the atherosclerotic lesion was alleviated with MET intervention. Moreover, parameters in AS including body weights (BWs), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and malondialdehyde (MDA) were elevated; whereas high-density lipoprotein (HDL) and total superoxide dismutase (T-SOD) levels were decreased, which could be reversed by MET intervention. Elevated pro-inflammatory interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccaride (LPS) in AS were decreased after MET administration. However, anti-inflammatory IL-10 showed no significant difference between AS group and AS+MET group. Consistently, accumulated macrophages in the aorta of AS were conversely lowered with MET treatment. The results of 16S rRNA sequencing and analysis displayed that the overall community of gut microbiota in AS was notably changed with MET treatment mainly through decreasing Firmicutes, Proteobacteria, Romboutsia, Firmicutes/Bacteroidetes, as well as increasing Akkermansia, Bacteroidetes, Bifidobacterium. Additionally, we found that microbiota-derived short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and valeric acid in AS were decreased, which were significantly up-regulated with MET intervention. Consistent with the attenuation of MET on gut dysbiosis, decreased intestinal tight junction protein zonula occludens-1 (ZO)-1 in AS was restored after MET supplementation. Correlation analysis showed close relationships among gut bacteria, microbial metabolites SCFAs and inflammation. Collectively, MET intervention ameliorates AS in ApoE-/- mice through restoring gut dysbiosis and anti-inflammation, thus can potentially serve as an inexpensive and effective intervention for the control of the atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]