Poria cocos Polysaccharide Ameliorated Antibiotic-Associated Diarrhea in Mice via Regulating the Homeostasis of the Gut Microbiota and Intestinal Mucosal Barrier.

Poria cocos polysaccharides (PCP) have been validated for several biological activities, including antitumor, anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective and modulation on gut microbiota. In this research, we aim to demonstrate the potential prebiotic effects and the therapeutic efficacies of PCP in the treatment of antibiotic-associated diarrhea (AAD), and confirm the beneficial effects of PCP on gut dysbiosis. Antibiotic-associated diarrhea mice models were established by treating them with broad-spectrum antibiotics in drinking water for seven days. Mice in two groups treated with probiotics and polysaccharide were given Bifico capsules (4.2 g/kg/d) and PCP (250 mg/kg/d) for seven days using intragastric gavage, respectively. To observe the regulatory effects of PCP on gut microbiota and intestinal mucosal barrier, we conducted the following experiments: intestinal flora analysis (16S rDNA sequencing), histology (H&E staining) and tight junction proteins (immunofluorescence staining). The levels of mRNA expression of receptors associated with inflammation and gut metabolism were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The study revealed that PCP can comprehensively improve the clinical symptoms of AAD mice, including fecal traits, mental state, hair quality, etc., similar to the effect of probiotics. Based on histology observation, PCP significantly improved the substantial structure of the intestine of AAD mice by increasing the expression levels of colonic tight junction protein zonula-occludens 1 (ZO-1) and its mRNA. Moreover, PCP not only increased the abundance of gut microbiota, but also increased the diversity of gut microbiota in AAD mice, including alpha diversity and beta diversity. Further analysis found that PCP can modulate seven characteristic species of intestinal flora in AAD mice, including Parabacteroides_distasonis, Akkermansia_muciniphila, Clostridium_saccharolyticum, Ruminoc-occus_gnavus, Lactobacillus_salivarius, Salmonella_enterica and Mucispirillum_schaedleri. Finally, enrichment analysis predicted that PCP may affect intestinal mucosal barrier function, host immune response and metabolic function by regulating the microbiota. RT-PCR experiments showed that PCP can participate in immunomodulatory and modulation on metabolic by regulating the mRNA expression of forkhead-box protein 3 (FOXP3) and G protein-coupled receptor 41 (GPR41). These results indicated that Poria cocos polysaccharide may ameliorate antibiotic-associated diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier. In addition, polysaccharide-derived changes in intestinal microbiota were involved in the immunomodulatory activities and modulation of the metabolism.

Engineering a Self-Grown TiO2 /Ti-MOF Heterojunction with Selectively Anchored High-Density Pt Single-Atomic Cocatalysts for Efficient Visible-Light-Driven Hydrogen Evolution.

A photocatalyst TiO2 /Ti-BPDC-Pt is developed with a self-grown TiO2 /Ti-metal-organic framework (MOF) heterojunction, i.e., TiO2 /Ti-BPDC, and selectively anchored high-density Pt single-atomic cocatalysts on Ti-BPDC for photocatalytic hydrogen evolution. This intimate heterojunction, growing from the surface pyrolytic reconstruction of Ti-BPDC, works in a direct Z-scheme, efficiently separating electrons and holes. Pt is selectively anchored on Ti-BPDC by ligands and is found in the form of single atoms with loading up to 1.8 wt %. The selective location of Pt is the electron-enriched domain of the heterojunction, which further enhances the utilization of the separated electrons. This tailored TiO2 /Ti-BPDC-Pt shows a significantly enhanced activity of 12.4 mmol g-1 h-1 compared to other TiO2 - or MOF-based catalysts. The structure-activity relationship further proves the balance of two simultaneously exposed domains of heterojunctions is critical to fulfilling this kind of catalyst.

Operando Elucidation of Electrocatalytic and Redox Mechanisms on a 2D Metal Organic Framework Catalyst for Efficient Electrosynthesis of Hydrogen Peroxide in Neutral Media.

The practical electrosynthesis of hydrogen peroxide (H2O2) is hindered by the lack of inexpensive and efficient catalysts for the two-electron oxygen reduction reaction (2e- ORR) in neutral electrolytes. Here, we show that Ni3HAB2 (HAB = hexaaminobenzene), a two-dimensional metal organic framework (MOF), is a selective and active 2e- ORR catalyst in buffered neutral electrolytes with a linker-based redox feature that dynamically affects the ORR behaviors. Rotating ring-disk electrode measurements reveal that Ni3HAB2 has high selectivity for 2e- ORR (>80% at 0.6 V vs RHE) but lower Faradaic efficiency due to this linker redox process. Operando X-ray absorption spectroscopy measurements reveal that under argon gas the charging of the organic linkers causes a dynamic Ni oxidation state, but in O2-saturated conditions, the electronic and physical structures of Ni3HAB2 change little and oxygen-containing species strongly adsorb at potentials more cathodic than the reduction potential of the organic linker (Eredox ∼ 0.3 V vs RHE). We hypothesize that a primary 2e- ORR mechanism occurs directly on the organic linkers (rather than the Ni) when E > Eredox, but when E < Eredox, H2O2 production can also occur through Ni-mediated linker discharge. By operating the bulk electrosynthesis at a low overpotential (0.4 V vs RHE), up to 662 ppm of H2O2 can be produced in a buffered neutral solution in an H-cell due to minimized strong adsorption of oxygenates. This work demonstrates the potential of conductive MOF catalysts for 2e- ORR and the importance of understanding catalytic active sites under electrochemical operation.

Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex.

Acetylation is correlated with chromatin decondensation and transcriptional activation, but its regulation by histone deacetylase (HDAC)-bearing corepressor complexes is poorly understood. Here, we describe the mechanism of assembly of the mammalian Sin3L/Rpd3L complex facilitated by Sds3, a conserved subunit deemed critical for proper assembly. Sds3 engages a globular, helical region of the HDAC interaction domain (HID) of the scaffolding protein Sin3A through a bipartite motif comprising a helix and an adjacent extended segment. Sds3 dimerizes through not only one of the predicted coiled-coil motifs but also, the segment preceding it, forming an ∼ 150-Å-long antiparallel dimer. Contrary to previous findings in yeast, Sin3A rather than Sds3 functions in recruiting HDAC1 into the complex by engaging the latter through a highly conserved segment adjacent to the helical HID subdomain. In the resulting model for the ternary complex, the two copies of the HDACs are situated distally and dynamically because of a natively unstructured linker connecting the dimerization domain and the Sin3A interaction domain of Sds3; these features contrast with the static organization described previously for the NuRD (nucleosome remodeling and deacetylase) complex. The Sds3 linker features several conserved basic residues that could potentially maintain the complex on chromatin by nonspecific interactions with DNA after initial recruitment by sequence-specific DNA-binding repressors.

Toxic Effects of Bisphenol AF Exposure on the Reproduction and Liver of Female Marine Medaka (Oryzias melastigma).

In recent years, bisphenol AF (BPAF) in aquatic environments has drawn attention to its ecological risks. This study aims to investigate the toxic effects of BPAF (188.33 µg/L) exposure for 30 days on female marine medaka (Oryzias melastigma). On the 10th and 30th day of exposure, the toxicity was evaluated using histological analysis of the liver and ovaries and the transcription levels of genes related to the antioxidant system, immune system, and hypothalamic-pituitary-gonadal (HPG) axis. Findings revealed that (1) BPAF exposure caused vacuolation, karyopyknosis and karyolysis in the liver of marine medaka, and the toxic impact augmented with duration; (2) exposure to BPAF for 10 days facilitated the growth and maturation of primary ova, and this exposure had a comparatively inhibitory effect after 30 days; (3) exposure to BPAF resulted in a biphasic regulation of the transcriptional abundance of genes involved in antioxidant and inflammatory response (e.g., il-8, cat), with an initial up-regulation followed by down-regulation. Additionally, it disrupted the transcriptional pattern of HPG axis-related genes (e.g., 3ßhsd, arα). In conclusion, 188.33 µg/L BPAF can alter the expression levels of functionally related genes, impair the structural integrity of marine organisms, and pose a threat to their overall health.

Spectroscopic Characterization of Mn1+ Low Oxidation State in Prussian Blue-Based Battery Anodes.

Stabilization of ions in exotic oxidation states is beneficial for the development of new materials for green energy technologies. Exotic Mn1+ was proposed to play a role in the function of sodium-based Prussian blue analogues (PBA) batteries, a highly sought-out technology for industrial energy storage. Here, we report the detailed electronic structure characterization of uncharged and charged sodium-based manganese hexacyanomanganate anodes via Mn K-edge X-ray absorption spectroscopy (XAS), Kß nonresonant X-ray emission (XES), and resonant inelastic X-ray scattering (RIXS). The latter allowed us to obtain site-selective XANES information about two distinct Mn centers. The obtained spectroscopic data represent the first electronic structure characterization of low-spin Mn1+ using hard X-ray RIXS and XES and allowed us to confirm its role in anode reduction. Our experimental approach can be expanded to analysis of analogues with other 3d transition metals broadening the application of exotic ionic states in materials engineering.

The role of oxygen in automotive grade lithium-ion battery cathodes: an atomistic survey of ageing.

The rising demand for high-performance lithium-ion batteries, pivotal to electric transportation, hinges on key materials like the Ni-rich layered oxide LiNixCoyAlzO2 (NCA) used in cathodes. The present study investigates the redox mechanisms, with particular focus on the role of oxygen in commercial NCA electrodes, both fresh and aged under various conditions (aged cells have performed >900 cycles until a cathode capacity retention of ∼80%). Our findings reveal that oxygen participates in charge compensation during NCA delithiation, both through changes in transition metal (TM)-O bond hybridization and formation of partially reversible O2, the latter occurs already below 3.8 V vs. Li/Li+. Aged NCA material undergoes more significant changes in TM-O bond hybridization when cycling above 50% SoC, while reversible O2 formation is maintained. Nickel is found to be redox active throughout the entire delithiation and shows a more classical oxidation state change during cycling with smaller changes in the Ni-O hybridization. By contrast, Co redox activity relies on a stronger change in Co-O hybridization, with only smaller Co oxidation state changes. The Ni-O bond displays an almost twice as large change in its bond length on cycling as the Co-O bond. The Ni-O6 octahedra are similar in size to the Co-O6 octahedra in the delithiated state, but are larger in the lithiated state, a size difference that increases with battery ageing. These contrasting redox activities are reflected directly in structural changes. The NCA material exhibits the formation of nanopores upon ageing, and a possible connection to oxygen redox activity is discussed. The difference in interaction of Ni and Co with oxygen provides a key understanding of the mechanism and the electrochemical instability of Ni-rich layered transition metal oxide electrodes. Our research specifically highlights the significance of the role of oxygen in the electrochemical performance of electric-vehicle-grade NCA electrodes, offering important insights for the creation of next-generation long-lived lithium-ion batteries.

Optimal control of the SIR model with constrained policy, with an application to COVID-19.

This article considers the optimal control of the SIR model with both transmission and treatment uncertainty. It follows the model presented in Gatto and Schellhorn (2021). We make four significant improvements on the latter paper. First, we prove the existence of a solution to the model. Second, our interpretation of the control is more realistic: while in Gatto and Schellhorn (2021) the control α is the proportion of the population that takes a basic dose of treatment, so that α>1 occurs only if some patients take more than a basic dose, in our paper, α is constrained between zero and one, and represents thus the proportion of the population undergoing treatment. Third, we provide a complete solution for the moderate infection regime (with constant treatment). Finally, we give a thorough interpretation of the control in the moderate infection regime, while Gatto and Schellhorn (2021) focused on the interpretation of the low infection regime. Finally, we compare the efficiency of our control to curb the COVID-19 epidemic to other types of control.

Who determines United States Healthcare out-of-pocket costs? Factor ranking and selection using ensemble learning.

PURPOSE: Healthcare out-of-pocket (OOP) costs consist of the annual expenses paid by individuals or families that are not reimbursed by insurance. In the U.S, broadening healthcare disparities are caused by the rapid increase in OOP costs. With a precise forecast of the OOP costs, governments can improve the design of healthcare policies to better control the OOP costs. This study designs a purely data-driven ensemble learning procedure to achieve a collection of factors that best predict OOP costs. METHODS: We propose a voting ensemble learning procedure to rank and select factors of OOP costs based on the Medical Expenditure Panel Survey dataset. The method involves utilizing votes from the base learners forward subset selection, backward subset selection, random forest, and LASSO. RESULTS: The top-ranking factors selected by our proposed method are insurance type, age, asthma, family size, race, and number of physician office visits. The predictive models using these factors outperform the models that employ the factors commonly considered by the literature through improving the prediction error (test MSE of the OOP costs' log-odds) from 0.462 to 0.382. CONCLUSION: Our results indicate a set of factors which best explain the OOP costs behavior based on a purely data-driven solution. These findings contribute to the discussions regarding demand-side needs for containing rapidly rising OOP costs. Instead of estimating the impact of a single factor on OOP costs, our proposed method allows for the selection of arbitrary-sized factors to best explain OOP costs.

Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rats [corrected].

The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-Dawley rats each were subjected to ovariectomized (OVX) or sham surgery and treated orally once daily with herbal extracts or vehicle. Body weight was recorded weekly, and blood samples were collected from fasting animals at different time points. Biochemical markers of bone resorption and cartilage degradation were analyzed. Changes in bone mineral density and calcium content were determined in the femoral center and femoral telocentric end of rats. Out of 56 TCM herbs/roots extracts, only kudzu root demonstrated consistent joint protective effects. OVX resulted in a marked increase in bone resorption and cartilage degradation, which could be significantly reversed by kudzu after three weeks of treatment. Compared to vehicle, kudzu induced a significant increase in bone mineral density in the femoral center and femoral telocentric end, and calcium content. The results show that kudzu exerts direct effects on articular cartilage in the OVX rat and can effectively prevent the acceleration of cartilage degradation induced by ovariectomy. Moreover, kudzu has demonstrated positive effects on metabolic health (cause a weight reduction) and may represent a possible treatment for OP and OA with high body mass index. Further studies are needed to investigate the potential effects of kudzu root in postmenopausal women.

Erratum: Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rats.

[This corrects the article on p. 3517 in vol. 9, PMID: 28804568.].

Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells.

4-Demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), a new podophyllotoxin glucoside, was isolated from the rhizomes of Sinopodophyllum emodi (Wall.) Ying and showed cytotoxic effects in human carcinoma cells. Among the target cells (HeLa, A2 and SH-SY5Y), the cytotoxic effects of 4DPG showed dose- and time-dependency. Furthermore, the cervical carcinoma cell line, HeLa, was more sensitive to 4DPG. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at the G1 phase, and a concomitant increase of cell population at the G2/M phase. 4DPG also caused DNA fragmentation in HeLa cells. Treatment with 0.1 microM 4DPG increased p53 expression and Bax/Bcl-2 ratio in HeLa cells, as well as in A2 cells. These results suggested that 4DPG-induced apoptosis might be through a p53-dependent pathway.