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Proper membrane physiology requires maintenance of biophysical properties, which must be buffered from external perturbations. While homeostatic adaptation of membrane fluidity to temperature variation is a ubiquitous feature of ectothermic organisms, such responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we report that challenging mammalian membranes by dietary lipids leads to robust lipidomic remodeling to preserve membrane physical properties. Specifically, exogenous polyunsaturated fatty acids are rapidly incorporated into membrane lipids, inducing a reduction in membrane packing. These effects are rapidly compensated both in culture and in vivo by lipidome-wide remodeling, most notably upregulation of saturated lipids and cholesterol, resulting in recovery of membrane packing and permeability. Abrogation of this response results in cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential mammalian mechanism for membrane homeostasis wherein lipidome remodeling in response to dietary lipid inputs preserves functional membrane phenotypes. Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.

Background Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis and treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current theorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still largely unknown. Recently, biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we summarized the latest progress of biliatresone research in BA and tried to answer the question of whether it could provide further clues to the etiology of human BA. Data sources We conducted a PubMed search for any published articles related to the topic using search terms including “biliary atresia”, “biliatresone”, “GSH”, and “HSP90”. Relevant data were extracted from the original text or supplementary materials of the corresponding articles. Results Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors involved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epidemiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occurrence of biliary atresia is partly due to biliatresone or its structure-like compounds depositing in human body via vegetables or/and the altered intestinal flora structure can be tentatively established. Conclusions Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA, and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered intestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. However, the evidence from large sample epidemiological research is necessary.

Liuwei Dihuang pills (LW) are widely used as the traditional tonic prescription for the treatment of diabetes and diabetic kidney disease (DKD). This study aimed to investigate the potential mechanism underlying LW-mediated prevention and treatment of DKD from the perspective of host-gut microbiome co-metabolism. A rat model of DKD was established using high-fat diet and streptozotocin. Levels of type IV collagen (Col IV), fibronectin (FN), laminin (Lam), transforming growth factor-β (TGF-β), SMAD family member 7 (SMAD7), and SMAD3 in the kidneys were determined by real time-polymerase chain reaction and Western blot. Fecal metabolites were profiled using ultra-high-performance liquid chromatography-tandem mass spectrometry. Metagenomic sequencing of the feces was performed using high-throughput sequencing. When combined with metformin (MET)-based therapy, LW significantly improved serum creatinine and blood urea nitrogen levels, kidney index, 24-h urine volume, urine protein content and excretion rate, and urinary creatinine and cystatin C levels. It also attenuated morphological changes. Correspondingly, LW intervention reduced the renal expression of TGF-β, SMAD3, Col IV, LAM, FN, interleukin (IL)-6, and IL-1β, while increasing SMAD7 expression. Additionally, it normalized metabolic pathway abnormalities in galactose, butyric acid, fructose, mannose, amino sugar, and nucleotide sugar metabolism. Moreover, LW regulated bacterial imbalances, notably in specific species such as , , , , sp. , , , , , and . The combination of LW and MET ameliorated renal impairment in DKD rats by regulating the TGF-β/SMAD signaling pathway, metabolic disturbances in endogenous metabolites, and gut microbiota dysbiosis.

Background Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context. Methods Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies. Results We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status. Conclusions The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples.

Objective Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. Methods The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. Results We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach’s α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p  < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p  = 0.030, d = 0.125), physical pain (t = 7.880, p  < 0.001,d = 0.436), psychological discomfort (t = 8.993, p  < 0.001, d = 0.514), physical disability (t = 6.343, p  < 0.001, d = 0.358), psychological disability (t = 5.592, p  < 0.001, d = 0.315), social disability (t = 5.301, p  < 0.001,d = 0.304), social handicap (t = 4.452, p  < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p  = 0.002, d = 0.280), psychological discomfort (t = 2.478, p  = 0.014, d = 0.222), and psychological disability (t = 2.067, p  = 0.039, d = 0.188). Conclusion This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

The fatty acid desaturase 1 (FADS1), also known as delta‐5 desaturase (D5D), is one of the rate‐limiting enzymes involved in the desaturation and elongation cascade of polyunsaturated fatty acids (PUFAs) to generate long‐chain PUFAs (LC‐PUFAs). Reduced function of D5D and decreased hepatic FADS1 expression, as well as low levels of LC‐PUFAs, were associated with nonalcoholic fatty liver disease. However, the causal role of D5D in hepatic lipid homeostasis remains unclear. In this study, we hypothesized that down‐regulation of FADS1 increases susceptibility to hepatic lipid accumulation. We used in vitro and in vivo models to test this hypothesis and to delineate the molecular mechanisms mediating the effect of reduced FADS1 function. Our study demonstrated that FADS1 knockdown significantly reduced cellular levels of LC‐PUFAs and increased lipid accumulation and lipid droplet formation in HepG2 cells. The lipid accumulation was associated with significant alterations in multiple pathways involved in lipid homeostasis, especially fatty acid oxidation. These effects were demonstrated to be mediated by the reduced function of the peroxisome proliferator–activated receptor alpha (PPARα)–fibroblast growth factor 21 (FGF21) axis, which can be reversed by treatment with docosahexaenoic acid, PPARα agonist, or FGF21. In vivo, FADS1‐knockout mice fed with high‐fat diet developed increased hepatic steatosis as compared with their wild‐type littermates. Molecular analyses of the mouse liver tissue largely corroborated the observations in vitro, especially along with reduced protein expression of PPARα and FGF21. Conclusion: Collectively, these results suggest that dysregulation in FADS1 alters liver lipid homeostasis in the liver by down‐regulating the PPARα‐FGF21 signaling axis.

Olanzapine is a commonly used drug in the treatment of schizophrenia, but the mechanism of abnormal bone metabolism caused by olanzapine is still unclear. The change of microflora may be an important factor leading to the change of bone metabolism. Therefore, the purpose of this study was to explore a plausible hypothesis that olanzapine may aggravate abnormal bone metabolism and cause bacterial imbalance in patients with schizophrenia. This study intervened in mice by gavage with olanzapine to detect changes in alveolar bone tissue and oral microbiota. The effect of related bacteria on osteogenesis was further examined. The results showed that increased, the bone mass and type I collagen of alveolar bone decreased. lipoteichoic acid (LTA) inhibited osteogenic differentiation and up-regulated gene expression. gene can down-regulate the expression of gene, and the proteins encoded by the two may interact. Olanzapine may increase the relative abundance of oral , whose components are plausibly linked to increased expression of gene and inhibition of bone formation through extracellular matrix-related pathways. These exploratory findings support further exploration of microbiota-based strategies to alleviate skeletal complications and promote oral health. The clinical research presented in this paper has been registered on ClinicalTrials.gov, a platform of the U.S. National Institutes of Health (Registration Number: NCT06123897; URL: https://clinicaltrials.gov/ct2/show/NCT06123897), with the registration date of November 9, 2023.

Background Breast cancer is a leading cause of cancer-related death for women in the USA. Thus, there is an increasing need to investigate novel prognostic markers and therapeutic methods. Inflammation raises challenges in treating and preventing the spread of breast cancer. Specifically, the nuclear factor kappa b (NFκB) pathway contributes to cancer progression by stimulating proliferation and preventing apoptosis. One target gene of this pathway is PTGS2 , which encodes for cyclooxygenase 2 (COX-2) and is upregulated in 40% of human breast carcinomas. COX-2 is an enzyme involved in the production of prostaglandins, which mediate inflammation. Here, we investigate the effect of Singleminded-2s (SIM2s), a transcriptional tumor suppressor that is implicated in inhibition of tumor growth and metastasis, in regulating NFκB signaling and COX-2. Methods For in vitro experiments, reporter luciferase assays were utilized in MCF7 cells to investigate promoter activity of NFκB and SIM2. Real-time PCR, immunoblotting, immunohistochemistry, and chromatin immunoprecipitation assays were performed in SUM159 and MCF7 cells. For in vivo experiments, MCF10DCIS.COM cells stably expressing SIM2s-FLAG or shPTGS2 were injected into SCID mice and subsequent tumors harvested for immunostaining and analysis. Results Our results reveal that SIM2 attenuates the activation of NFκB as measured using NFκB-luciferase reporter assay. Furthermore, immunostaining of lysates from breast cancer cells overexpressing SIM2s showed reduction in various NFκB signaling proteins, as well as pAkt, whereas knockdown of SIM2 revealed increases in NFκB signaling proteins and pAkt. Additionally, we show that NFκB signaling can act in a reciprocal manner to decrease expression of SIM2s . Likewise, suppressing NFκB translocation in DCIS.COM cells increased SIM2s expression . We also found that NFκB / p65 represses SIM2 in a dose-dependent manner, and when NFκB is suppressed, the effect on the SIM2 is negated. Additionally, our ChIP analysis confirms that NFκB/p65 binds directly to SIM2 promoter site and that the NFκB sites in the SIM2 promoter are required for NFκB-mediated suppression of SIM2s. Finally, overexpression of SIM2s decreases PTGS2 in vitro, and COX-2 staining in vivo while decreasing PTGS2 and/or COX-2 activity results in re-expression of SIM2. Conclusion Our findings identify a novel role for SIM2s in NFκB signaling and COX-2 expression.

The operation of cascade reservoir systems has altered river hydrology and sediment distribution patterns. In this study, 31 surface water and sediment samples were collected from the Heihe River from July to August in 2019 and 2020 to investigate the spatial distribution and sources of heavy metals and assess their ecological risks. The results revealed that the concentrations of heavy metals in surface water were much lower than the quality standards for surface water in China, and there were no significant differences in the natural reaches, center and tail of the reservoir. Cd in surface sediments was at a heavy contamination and high risk level, and the heavy metal pollution levels in the main streams and tributaries differed greatly, especially in the graded reservoirs with a gradual accumulation trend. This may be related to the fact that there were many fine-grained sediments in the reservoir center near the dam. Factor analysis-multiple linear regression (FA-MLR) revealed that heavy metals mainly come from natural factors and anthropogenic input, with anthropogenic inputs mainly coming from mining activities in the tributaries and industrial and agricultural activities in the main stream.

Background Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo. Result The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11–7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects. Conclusion These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.