Abstract
Dimerization of C-type lectin receptors (CLRs) or Toll-like receptors (TLRs) can alter their ligand binding ability, thereby modulating immune responses. However, the possibilities and roles ...of dimerization between CLRs and TLRs remain unclear. Here we show that C-type lectin receptor-2d (CLEC2D) forms homodimers, as well as heterodimers with TLR2. Quantitative ligand binding assays reveal that both CLEC2D homodimers and CLEC2D/TLR2 heterodimers have a higher binding ability to fungi-derived β-glucans than TLR2 homodimers. Moreover, homo- or hetero-dimeric CLEC2D mediates β-glucan-induced ubiquitination and degradation of MyD88 to inhibit the activation of transcription factor IRF5 and subsequent IL-12 production.
Clec2d
-deficient female mice are resistant to infection with
Candida albicans
, a human fungal pathogen, owing to the increase of IL-12 production and subsequent generation of IFN-γ-producing NK cells. Together, these data indicate that CLEC2D forms homodimers or heterodimers with TLR2, which negatively regulate antifungal immunity through suppression of IRF5-mediated IL-12 production. These homo- and hetero-dimers of CLEC2D and TLR2 provide an example of receptor dimerization to regulate host innate immunity against microbial infections.
The triglyceride-glucose (TyG) index has been proposed as a surrogate marker of insulin resistance. However, the relationship between the TyG index and central blood pressure (BP), has not been well ...studied in adults.
A total of 715 Chinese adult participants were enrolled in this study. Anthropometric and BP were assessed. The TyG index was calculated as lnfasting triglycerides(mg/dL) × fasting glucose(mg/dL)/2. Central BP was measured using SphygmoCor system.
The participants were stratified into three groups based on the TyG index, and significant differences were observed in metabolic and cardiovascular parameters and the prevalence of hypertension among the groups. Both brachial (β = 1.38, P = 0.0310; group highest vs. lowest, β = 2.66, P = 0.0084) and aortic (β = 2.38, P = 0.0002; group highest vs. lowest, β = 3.96, P = 0.0001) diastolic BP were significantly and independently associated with the TyG index and increasing TyG index tertile. However, there was no independent association between the TyG index and systolic BP. A one-unit increase in the TyG index was associated with a 46% higher risk of hypertension (P = 0.0121), and compared with the lowest group, participants in the highest group had a 95% higher risk of hypertension (P = 0.0057).
Our study demonstrates a significant and independent association between the TyG index and both brachial and aortic diastolic BP in Chinese adults. Furthermore, the TyG index was found to be an independent predictor of hypertension.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ...ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up‐regulating proliferating cell nuclear antigen (PCNA) and proliferation‐related Ki–67 antigen (Ki–67) to promote proliferation of MCF–7 cells. In addition, 17–β–estradiol (E2) enhances ERα‐induced proliferation of MCF–7 cells by stimulating expression of PCNA and Ki–67. Knockdown of ERα significantly affects PCNA/Ki–67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element‐dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF–7 cells by up‐regulating miR–17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.
Model for how estrogen receptor α (ERα) regulates MCF‐7 cell proliferation by p53‐p21‐PCNA‐E2F1 pathway.
Klotho, an important anti-aging protein, may be related to elevated blood pressure (BP) and arterial stiffness. We aimed to investigate associations between the serum klotho concentration and ...peripheral/central BP and arterial stiffness based on the carotid-femoral pulse wave velocity (cfPWV) in a Chinese population. We invited all inhabitants aged ≥ 18 years in two Dali communities for participation. The SphygmoCor system was used to record radial arterial waveforms. Aortic waveforms were derived using a generalized transfer function. The central BP was assessed by calibrating the brachial BP, which was measured using an oscillometric device. The serum klotho concentration was measured using an enzyme-linked immunosorbent assay and logarithmically transformed. Of the 716 participants (mean age: 51.9 ± 12.6 years), 467 (65.2%) were women. The median serum klotho concentration was 381.8 pg/mL. The serum klotho concentration did not significantly differ between patients with and without hypertension (P > 0.05) and between those with and without arterial stiffness (cfPWV ≥ 10 m/s) (P > 0.05). After adjusting for confounders, the serum klotho concentration was not significantly associated with the peripheral or central BP (P > 0.05) and cfPWV (P > 0.05). Our data indicated that the serum klotho concentration was not associated with BP or cfPWV in the general Chinese population.
Titanium dioxide is considered to be promising anode for sodium-ion batteries due to stable structure during the charge/discharge process. However, its practical application is hindered by the slow ...electron/ion transport. Herein, phosphorus-doped anatase TiO
2
nanoparticles with oxygen vacancies are successfully synthesized and utilized as high-performance sodium-storage materials. The dual strategy of phosphorus-doping and oxygen vacancies can concurrently boost electronic conductivity and adjust ion diffusion kinetics. They significantly contribute to the improved rate performance (167 mAh·g
−1
at 20.0C) and stable cycling (95.9% after 2000 cycles at 20.0C). The proposed dual strategy can be potentially used to improve other oxide anodes for rechargeable batteries.
Phenolic compounds (PCs) could be applied to reduce reactive oxygen species (ROS) levels, and are used to prevent and treat diseases related to oxidative stress. QSAR study was applied to elucidate ...the relationship between the molecular descriptors and physicochemical properties of polyphenol analogues and their DPPH radical scavenging capability, to guide the design and discovery of highly-potent antioxidant substances more efficiently. PubMed database was used to collect 99 PCs with antioxidant activity, whereas, 105 negative PCs were found in ChEMBL database; their molecular descriptors were generated with Python's Rdkit package. While the molecular descriptors significantly related to the antioxidant activity of PCs were filtered by t-test. The prediction QSAR model was then established by discriminant analysis, and the obtained model was verified by the back-substitution and Leave-One-Out cross-validation methods along with heat map. It was revealed that the anti-DPPH radical activity of PCs was correlated with the drug-likeness and molecular fingerprints, physicochemical, topological, constitutional and electronic property. The established QSAR model could explicitly predict the antioxidant activity of polyphenols, thus were applicable to evaluate the potential of candidates as antioxidants.
Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky's disease and economic losses worldwide. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and are critical ...for the control of lipid homeostasis. However, the role of LXR in PRV infection has not been fully established. In this study, we found that PRV infection downregulated the mRNA and protein levels of LXRα and LXRβ in vitro and in vivo. Furthermore, we discovered that LXR activation suppressed PRV proliferation, while LXR inhibition promoted PRV proliferation. We demonstrated that LXR activation-mediated reduction of cellular cholesterol was critical for the dynamics of PRV entry-dependent clathrin-coated pits. Replenishment of cholesterol restored the dynamics of clathrin-coated pits and PRV entry under LXR activation conditions. Interestingly, T0901317, an LXR agonist, prevented PRV infection in mice. Our results support a model that PRV modulates LXR-regulated cholesterol metabolism to facilitate viral proliferation.
Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator; however, the effects of Pb contamination on P. crinitum rhizosphere soil enzymatic activities and microbial composition remain largely ...unexplored. Thus, an indoor experiment was conducted by cultivating P. crinitum seedlings and exposing them to four Pb concentrations (0, 1,000, 2000 and 3000 mg/kg Pb). Protease, urease, acid phosphatase and invertase activities were determined using standard methods while soil bacterial composition was determined by 16 S rDNA sequencing. The results showed that rhizosphere soil acid phosphatase activity significantly increased with increasing Pb concentration, while urease activity was significantly greater in rhizosphere soil contaminated with 1000 and 2000 mg/kg than in the control. There was a clear shift in bacterial composition during phytoremediation by P. crinitum. Compared to the control, Bacteroidetes was more abundant in all Pb-contaminated soils, Actinobacteria was more abundant in 1000 mg/kg Pb-treated soil, and Firmicutes was more abundant in 3000 mg/kg Pb-treated soil. Positive correlations were observed between dominant bacterial phyla and soil enzyme activities. Metabolic pathways, such as ABC transporter, quinine reductase, and ATP-binding protein were significantly increased in rhizosphere soil bacteria with Pb contamination. In conclusion, Pb contamination differentially influenced the activities of rhizosphere soil enzymes, specifically increasing acid phosphatase and urease activities, and alters the dominance of soil bacteria through up-regulation of genes related to some metabolic pathways. The strong correlations between dominant bacterial phyla and enzymatic activities suggest synergetic effects on the growth of P. crinitum during Pb contamination.
•Enzyme activities and bacterial community in rhizosphere soil of P. crinitum contaminated with Pb were studied.•Pb contamination significantly increased soil acid phosphatase and urease activities.•Pb contamination alters bacterial community composition in rhizosphere soil.•Positive correlations were observed between some soil bacteria and enzyme activities.•Pb contamination upregulated ABC transporter, quinine reductase and ATP-binding protein genes.
Ezrin-radixin-moesin (ERM) have been explored in many cancer processes. Moesin, as its component, has also been found to play an important role in the prognosis of cancer patients, tumor metastasis, ...drug resistance, and others. Especially in regulating the immunity, but most results came from direct studies on immune cells, there is no clear conclusion on whether moesin has similar effects in tumor cells. And moesin has certain research results in many cancers in other aspects, but there are few about moesin in lung adenocarcinoma (LUAD).
We detect the expression of moesin in 82 LUAD and matched normal tissue samples by immunohistochemistry. Besides, for the pathological feature, we did a detailed statistical analysis. And with the help of various databases, we have done in-depth exploration of moesin's ability to enhance the extent of immune lymphocyte infiltration.
Moesin is a poor expression in lung cancer tissues than the corresponding normal samples. And this phenomenon had a strongly associated with the prognosis and TNM stage of these LUAD patients. Moesin can enhance the infiltration of multiple immune lymphocytes in lung cancer. And this may be related to the interaction between moesin and various inflammatory molecules.
Moesin is a newly index for the prognosis of LUAD and improves the prognosis of LUAD patients by regulating a variety of inflammation-related molecules to enhance immune lymphocytes infiltration.
Thyroid dysfunction plays a role in blood pressure (BP) regulation. However, the associations between thyroid function and BP and arterial stiffness in the general Chinese population without thyroid ...disease are unknown. This population‐based cross‐sectional study aimed to investigate the association between thyroid function and peripheral and central BP and arterial stiffness in Chinese individuals. After excluding those who had thyroid diseases or incomplete clinical measurements, this study included 691 participants. Of the participants, 444 (64.2%) were women and 215 (31.1%) had hypertension. After adjustment for covariates, serum FT3 was significantly associated with a higher pulse rate in both sexes. In men, each 2.72‐fold increase in serum FT4 levels was associated with higher peripheral systolic BP (+10.82 mmHg, p = .005) and pulse pressure (+5.71 mmHg, p = .03). Each 2.72‐fold increase in serum FT4 levels was associated with higher central systolic BP (+8.03 mmHg, p = .03) and pulse pressure (+3.89 mmHg, p = .05). In women, serum FT4 was only associated with a higher central pulse pressure (+2.96 mmHg, p = .04). After adjustment for covariates, serum FT4 was significantly associated with a faster cfPWV exclusively in men. Our study showed that serum FT4 is associated with higher peripheral and central BP and faster cfPWV in men, whereas serum FT3 is positively associated with a higher pulse rate in both sexes, indicating that the effects of thyroid function on BP and arterial stiffness are more significant in men than in women.
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