Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

[Study on mechanism of Aconitum pendulum in treating rheumatoid arthritis based on toxicity efficacy evaluation and metabonomics].

The study aims to investigate the effects and potential mechanism of raw and processed Aconitum pendulum Busch on rheumatoid arthritis(RA) and analyze their toxicity attenuating and efficacy retaining effects. The bovine type Ⅱ collagen-induced arthritis(CIA) rat model was established. The weight, cardiac index, immune organ index, and arthritis index of the rats were recorded and calculated after administration. ELISA was used to measure the expressions of creatine kinase(CK), cardiac troponin T(cTnT), and multiple factors. The pathological morphological changes in heart tissue and ankle joint tissue were observed by hematoxylin-eosin staining. Connexin 43(Cx43) expression in the hearts of CIA rats was detected via immunohistochemical method. The levels of endogenous metabolites in the serum of CIA rats were detected by UPLC-Q-TOF-MS. Potential biomarkers were screened, and related metabolic pathways were analyzed. The results showed that raw A. pendulum could induce local myocardial fiber degeneration and necrosis, increase the cardiac index, decrease the average positive area of Cx43 expression significantly, and increase the expressions of CK and cTnT in cardiac tissue of rats. Meanwhile, raw A. pendulum could decrease the immune organ index, interleukin-6(IL-6), and other inflammatory cytokine contents in the serum and improve the damaged synovium and joint surface of CIA rats, with toxicity and efficacy coexisting. The Zanba stir-fired A. pendulum could reduce the index of arthritis, immune organ index, and content of IL-6 and inflammatory cytokines in serum and improve damaged synovium and joint surface of CIA rats with no obvious cardiac toxicity, showing significant toxicity attenuating and efficacy retaining effects. A total of 19 potential biomarkers of raw A. pendulum and Zanba stir-fired A. pendulum against RA were screened by serum metabolomics, including glycerophospholipid metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and steroid hormone synthesis. In conclusion, Xizang medicine A. pendulum is preventive and curative for RA. Raw A. pendulum has certain cardiotoxicity, and Zanba stir-fired A. pendulum has significant toxicity attenuating and efficacy retaining effects. The anti-RA mechanism may be related to the regulation of glycerophospholipid and amino acid metabolism.

Temporal and spatial variations in the sub-daily precipitation structure over the Qinghai-Tibet Plateau (QTP).

Precipitation is a vital component of the global atmospheric and hydrological cycles and influencing the distribution of water resources. Even subtle changes in precipitation can significantly impact ecosystems, energy cycles, agricultural production, and food security. Therefore, understanding the changes in the precipitation structure under climate change is essential. The Qinghai-Tibet Plateau (QTP) is a region sensitive to global climate change and profoundly impacts the atmospheric water cycle in Asia and even globally, rendering it a hot topic in climate change research in recent years. Few studies have examined on the sub-daily scale precipitation structure over the QTP. In this paper, the characteristics of sub-daily precipitation on the QTP were systematically investigated from multiple perspectives, including the concentration index, skewness (the third standardized moment of a distribution), and kurtosis (the fourth standardized moment of a distribution). The results indicated that the frequency of moderate-intensity nighttime precipitation on the QTP generally increased, and the analysis of both the concentration index and kurtosis (skewness) suggested that extreme precipitation was more frequent in the southwestern foothills of the QTP. Furthermore, potential high-risk areas for natural disasters were identified on the QTP, and found that the southeastern part of the plateau constituted a potential hotspot area for flood disasters. Given the complexity of climate change, a comprehensive analysis of the spatiotemporal characteristics of diurnal and nighttime precipitation changes on the QTP could help reveal the regularity of precipitation changes. This has significant implications for forecasting, warning, disaster preparedness, and mitigation efforts on the QTP.

[Effect of Film Mulching Age and Organic Fertilizer Application on the Distribution Characteristics of Microplastics in the Soil of a Peanut Field].

The large input of mulch film and organic fertilizer have led to increasingly serious microplastic pollution in farmland soil of China. In this study, the microplastic pollution of peanut farmland in Dezhou City, Shandong Province was investigated. The effects of different mulching years (0, 3, 5, and 8 years) and organic fertilizer application on the abundance, particle size, color, and shape of microplastics in farmland soil were analyzed. The results showed that the average abundances of microplastics in peanut soil were 65.33, 316.00, 1 098.67, and 1 346.34 n·kg-1, respectively, after 0, 3, 5, and 8 years of film mulching. The abundance of microplastics decreased with the increase in soil depth. The abundance of microplastics in 0-10, 10-20, and 20-30 cm topsoil was 1 076.00, 603.5, and 440.25 n·kg-1, respectively, and the abundance of microplastics increased significantly with increasing years of film mulching and organic fertilizer application (P<0.05). The particle size of microplastics in the sample plot <1 mm accounted for 77.30% of the total content, and with the increase in film mulching age, the proportion of microplastics with small particle size (<1 mm) increased significantly (P < 0.05). With the increase in soil depth, the proportion of microplastics with small particle size also gradually increased, whereas the application of organic fertilizer had no significant effect on the particle size of microplastics. The color of microplastics in the plot was mainly transparent (49.77%), followed by black (16.35%) and white (16.27%). The planting age and organic fertilizer application had no significant effect on the color of microplastics in the soil (P > 0.05), but the mulching age significantly increased the proportion of transparent microplastics. The abundance proportion of the five types of microplastics were 49.77%, 25.41%, 19.15%, 3.26%, and 2.41%, respectively. These field soil microplastics were mainly composed of polyethylene (PE), polypropylene (PP), and polystyrene (PS) polymers, accounting for 21.37%, 18.57%, and 19.77% of the total, respectively. Therefore, microplastics were widely present in the soil of the peanut field cultivated layer in Dezhou, Shandong, and the applications of mulch film and organic fertilizer were the main source. This study provides an important basis for the prevention and control of soil microplastic pollution in peanut fields.

Novel metal peroxide nanoboxes restrain Clostridioides difficile infection beyond the bactericidal and sporicidal activity.

Clostridioides difficile spores are considered as the major source responsible for the development of C. difficile infection (CDI), which is associated with an increased risk of death in patients and has become an important issue in infection control of nosocomial infections. Current treatment against CDI still relies on antibiotics, which also damage normal flora and increase the risk of CDI recurrence. Therefore, alternative therapies that are more effective against C. difficile bacteria and spores are urgently needed. Here, we designed an oxidation process using H2O2 containing PBS solution to generate Cl- and peroxide molecules that further process Ag and Au ions to form nanoboxes with Ag-Au peroxide coat covering Au shell and AgCl core (AgAu-based nanoboxes). The AgAu-based nanoboxes efficiently disrupted the membrane structure of bacteria/spores of C. difficile after 30-45 min exposure to the highly reactive Ag/Au peroxide surface of the nano structures. The Au-enclosed AgCl provided sustained suppression of the growth of 2 × 107 pathogenic Escherichia coli for up to 19 days. In a fecal bench ex vivo test and in vivo CDI murine model, biocompatibility and therapeutic efficacy of the AuAg nanoboxes to attenuate CDI was demonstrated by restoring the gut microbiota and colon mucosal structure. The treatment successfully rescued the CDI mice from death and prevented their recurrence mediated by vancomycin treatment. The significant outcomes indicated that the new peroxide-derived AgAu-based nanoboxes possess great potential for future translation into clinical application as a new alternative therapeutic strategy against CDI.

The In Vitro Effect of Psoralen on Glioma Based on Network Pharmacology and Potential Target Research.

Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in vitro glioma treatment experiments. First, we used network pharmacology to preliminarily predict the 21 core genes of psoralen in the treatment of glioma, including PIK3CA, PIK3CB, PIK3CG, and JAK2. The CCK-8 method was used to detect the effect of psoralen on the proliferation of glioma U87 and U251 cells, and the results showed that psoralen could significantly inhibit the proliferation of U87 and U251 cells. The flow cytometry was used to detect the apoptosis and cell cycle changes, and it was found that psoralen could significantly promote the early apoptosis of U87 and U251 cells and had a significant cycle arrest effect on the two cells. The cell scratch test showed that psoralen could significantly inhibit the migration of U87 and U251 cells. The relative expression levels of PIK3CA, PIK3CB, PIK3CG, and JAK2 were analyzed by Real-time Quantitative polymerase chain reaction (QT-PCR), and the results showed that psoralen could inhibit the gene expression of PIK3CA, PIK3CB, PIK3CG, and JAK2. Later, Western blotting (WB) experiments showed that psoralen could inhibit the protein expressions of PI3K and JAK2. This study has preliminarily explored and verified the antiglioma effect of psoralen in the form of inhibiting cell proliferation and migration, promoting cell apoptosis and organizing cell cycle in vitro. And may play a role by inhibiting the expression of PIK3CA, PIK3CB, PIK3CG, JAK2 gene and PI3K, JAK2 protein, psoralen has become a potential antiglioma drug.

Improved intergranular corrosion resistance of Al-Mg-Mn alloys with Sc and Zr additions.

Al-5.8Mg-0.4Mn with minor alloying additions of Sc and Zr was investigated via electrochemical testing and nitric acid mass loss testing (NAMLT) in order to reveal the influence of Sc and Zr upon sensitization and intergranular corrosion. The Al-Mg-Mn alloys were also analysed using an electron probe microanalyzer, indicating that ß-phase (Al3Mg2) was more likely to precipitate around rectangular or cubic Al6Mn particles. Results reveal that the strength and intergranular corrosion resistance of Al-5.8Mg-0.4Mn was improved by the combined addition of Sc and Zr. The Al3(Sc1-xZrx) dispersoids can lead to an alteration of the relative proportion of low angle grain boundaries, and lower volume fraction of ß-phase was observed for Al-5.8Mg-0.4Mn-xSc-yZr relative to the Sc and Zr free alloy.

Effect of pearling on composition, microstructure, water migration and cooking quality of highland barley (Hordeum vulgare var. Coeleste Linnaeus).

Highland barley (HB) has become popular due to its nutritional benefits, and pearling as a necessary process that could broaden its applications. The influence of pearling on the composition, microstructure, water migration and cooking characteristics of HB was investigated. With different degrees of pearling (DOPs), the levels of nutritious components except for starch and ß-glucan, decreased, and the ß-glucan content gradually increased and reached a plateau when the DOP was over 15%. Pearling can significantly shorten the cooking time by removing different tissues, and removal of the pericarp layer had significant influence by reducing the cooking time by 17 min (i.e., HB with DOP 5%). From the result of Peleg model fitting and low-field nuclear magnetic resonance spectroscopy, the saturated water absorption of HB did not differ for a DOP 5% and above, and cooking mainly increased the amount of moderately bound water and added small amount of bound water.

Resorcinol derivatives with α-glucosidase inhibitory activities from Syzygium samarangense.

Nine resorcinol derivatives including two new ones, 5-[(8Z,11Z,14Z)-nonadeca-8,11,14-trienyl] resorcinol (1) and 5-[(8Z,11Z,14E)-heptadeca-8,11,14-trienyl] resorcinol (2), were isolated from the leaves of Syzygium samarangense. The new structures were elucidated by means of extensive spectroscopic techniques including interpretation of 1D and 2D NMR spectra. Among them, compounds 3, 4, 6 and 7 exhibited significant α-glucosidase inhibitory activities with IC50 of 3.16, 3.16, 2.34 and 0.99 µM, respectively. This finding provides evidence that resorcinol derivatives with long aliphatic chain function as new promising antidiabetic alternatives.

Effect of freezing treatment of soybean on soymilk nutritional components, protein digestibility, and functional components.

Soymilk is a popular beverage in many countries owing to its nutrition and health effects. To increase household consumption of soymilk, instant soybeans were developed by freezing and subsequent drying pretreatment, which overcome the time-consuming need of soaking during soymilk preparation for home making. However, compared with the traditional soymilk making, the nutritional quality and functional properties of this soymilk made from the soybean by direct grinding in water without soaking are not clear yet. Soymilk made from untreated soybeans, soaked soybeans, and soaking, freezing, and air-drying soybeans (FADTS) were compared on their properties including nutritional components, in vitro protein digestibility, and functional components. It was found that FADTS was the best at extracting lipid and Ca, good at extracting of protein, carbohydrate, oligosaccharides, Fe, phytic acids, and tannins, and in producing soymilks with highest in vitro protein digestibility. The soluble protein and protein digestibility of FADTS (4 day) increased significantly from 44.4% and 78.5% of control to 56.2% and 85.0%, respectively. Soymilk from 4 days FADTS contained similar protein content and higher Fe content (4.40 mg/kg) compared to soaked sample (3.82 mg/kg). The results revealed that FADTS performed better at producing soymilk than untreated and soaked soybeans.

Vancomycin-Loaded Nanoparticles Enhance Sporicidal and Antibacterial Efficacy for Clostridium difficile Infection.

Current antibiotic treatments fail to eliminate the Clostridium difficile (C. difficile) spores and induce dysbiosis and intestinal inflammation via off-target effect, which causes refractory C. difficile infection raise an unmet need for a spore-specific antimicrobial treatment. We developed a sporicidal and antimicrobial vancomycin-loaded spore-targeting iron oxide nanoparticle (van-IONP) that selectively binds to C. difficile spores. Cryo-electron microscopy showed that vancomycin-loaded nanoparticles can target and completely cover spore surfaces. They not only successfully delayed the germination of the spores but also inhibited ∼50% of vegetative cell outgrowth after 48 h of incubation. The van-IONPs also inhibited the interaction of spores with HT-29 intestinal mucosal cells in vitro. In a murine model of C. difficile infection, the van-IONP significantly protected the mice from infected by C. difficile infection, reducing intestinal inflammation, and facilitated superior mucosal viability compared with equal doses of free vancomycin. This dual-function targeted delivery therapy showed advantages over traditional therapeutics in treating C. difficile infection.

New phloroglucinol derivatives with protein tyrosine phosphatase 1B (PTP1B) inhibitory activities from Syzygium austroyunnanense.

Five new phloroglucinol derivatives (1-5) together with one known analogue (6) were isolated from the leaves of Syzygium austroyunnanense which is an edible folk medicine used for the treatment of diabetes. The new structures were elucidated as austroyunones A - E (1-5) by means of the extensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR). Compounds 4-6 showed obvious protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. This discovery of new phloroglucinols and their bioactivities provided a scientific basis for the application of S. austroyunnanense as an edible and medicinal plant.

Non-high-density lipoprotein cholesterol: High-density lipoprotein cholesterol ratio is an independent risk factor for diabetes mellitus: Results from a population-based cohort study.

BACKGROUND: Dyslipidemia predicts the development and progression of diabetes. A higher non-high-density lipoprotein cholesterol (HDL-C): HDL-C ratio is reportedly associated with metabolic syndrome and insulin resistance, but its relationship with glycemic levels and diabetes remains unclear. METHODS: In all, 4882 subjects aged ≥40 years without diabetes and not using lipid-lowering drugs were enrolled in the study. The non-HDL-C: HDL-C ratio was log10 transformed to achieve normal distribution. Multivariate logistic regression was used to investigate the association between the log10 -transformed non-HDL-C: HDL-C ratio and diabetes. Stratified analyses of the association by age, gender, and body mass index (BMI) were also performed. RESULTS: After 3 years of follow-up, 704 participants developed diabetes. After adjustment for age, gender, current smoking, current drinking, physical activity, BMI, systolic blood pressure, and family history of diabetes, each 1-SD increase in the log(non-HDL-C: HDL-C ratio) was associated with higher fasting blood glucose (FPG) levels (ß = 0.1; 95% confidence interval [CI] 0.1-0.1), 2-h postload plasma glucose levels (2-h glucose; ß = 0.2; 95% CI 0.1-0.2), and risk of diabetes (odds ratio [OR] 1.1; 95% CI 1.0-1.2). In a multivariate model, subjects in the top quartile of non-HDL-C: HDL-C ratio had higher FPG (ß = 0.2; 95% CI 0.2-0.3), 2-h glucose (ß = 0.5; 95% CI 0.3-0.7) and HbA1c (ß = 0.1; 95% CI 0.1-0.2) levels, and a 40% increased risk of diabetes (OR 1.4; 95% CI 1.1-1.8) than participants in the bottom quartile. CONCLUSIONS: The non-HDL-C: HDL-C ratio was found to be an independent risk factor for diabetes.