Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia.

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate (AMP) to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse (GEM) model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery three days/week at 10mg/kg, beginning when the mice were two months old and lasting three months. We euthanized the mice at five months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single Cell RNA sequencing (scRNA-seq) of pancreata of AB-680 treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment.

Exploring factors influencing awareness and knowledge of human papillomavirus in Chinese college students: A cross-sectional study.

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV's transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV's association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22-24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.

Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease.

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis- regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.

Solid-State Electrolytes: Probing Interface Regulation from Multiple Perspectives.

Solid-state electrolytes (SSEs), as the heart of all-solid-state batteries (ASSBs), are recognized as the next-generation energy storage solution, offering high safety, extended cycle life, and superior energy density. SSEs play a pivotal role in ion transport and electron separation. Nonetheless, interface compatibility and stability issues pose significant obstacles to further enhancing ASSB performance. Extensive research has demonstrated that interface control methods can effectively elevate ASSB performance. This review delves into the advancements and recent progress of SSEs in interfacial engineering over the past years. We discuss the detailed effects of various regulation strategies and directions on performance, encompassing enhancing Li+ mobility, reducing energy barriers, immobilizing anions, introducing interlayers, and constructing unique structures. This review offers fresh perspectives on the development of high-performance lithium-metal ASSBs.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

Regional quality analysis of the hydrological environment with an improved random forest model based on the chimpanzee algorithm.

High-precision evaluations of water environment quality are highly important for improving the accuracy of early warning systems of regional water pollution risk and improving the regional water environment. This paper employs the chimp optimization algorithm (ChOA) to enhance the traditional random forest model, resulting in the chimp optimization algorithm-random forest (ChOA-RF) water quality assessment model for evaluating the Jiansanjiang area in Heilongjiang Province, China. The results show that the overall water environment in Jiansanjiang has the following characteristics: "The water quality of farms in the northwest is poor, and the quality of groundwater is better than that of surface water." Total nitrogen (TN) and total phosphorus (TP) in surface water and ammonium nitrogen (NH3-N), ferrum (Fe), and manganese (Mn) in groundwater are the main pollutants. The TP and TN in surface water and the NH3-N in groundwater exceeded the relevant standards, likely due to the excessive application of chemical fertilizers, especially nitrogen fertilizers. Additionally, Fe and Mn are harmful native substances. According to these findings, targeted improvement strategies, such as reducing nitrogen fertilizer application, plugging well, and increasing the surface water utilization rate, are proposed. Moreover, the ChOA-RF model is compared with the traditional empirical value model and the particle swarm optimization-random forest (PSO-RF) model. The results show that the ChOA-RF model can effectively reduce the root mean square error and mean absolute percentage error and improve the coefficient of determination. The running time and convergence ability are also better than those of the PSO-RF model, which is a more accurate and efficient machine learning model. The model can be used not only for high-precision evaluation of regional water environment quality but also for other machine learning fields.

Isoproterenol induced cardiac hypertrophy: A comparison of three doses and two delivery methods in C57BL/6J mice.

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective ß-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

Spin-coated and vacuum-processed hole-extracting self-assembled multilayers with H-aggregation for high-performance inverted perovskite solar cells.

We report a highly crystalline self-assembled multilayer (SAMUL) that is fundamentally different from the conventional monolayer or disordered bilayer used for hole-extraction in inverted perovskite solar cells (PSCs). The SAMUL can be easily formed on ITO substrate to form better surface coverage for enhancing the performance and stability of PSCs. A detailed structure-property-performance relationship of molecules used for SAMUL is established through a systematic study of their crystallinity, molecular packing, and hole-transporting properties. These SAMULs are rationally optimized by varying their molecular structures and deposition through thermal evaporation or spin-coating for fabricating PSCs. The CbzNaphPPA-based SAMUL was chosen for fabricating inverted PSCs due to its highest crystallinity and hole mobility derived from the ordered H-aggregation, which resulted in a remarkably high fill factor of 86.45%. This enables a very impressive power conversion efficiency (PCE) of 26.07% to be achieved along with excellent device stability (94% of its initial PCE retained after continuous operation for 1200 h under 1-sun irradiation at maximum power point at 65°C). Additionally, a record-high PCE of 23.50% could be achieved by adopting a thermally evaporated SAMUL. This greatly simplifies and broadens the scope for SAM to be used for large-area devices on diverse substrates.

LncRNA Nostrill promotes interferon-γ-stimulated gene transcription and facilitates intestinal epithelial cell-intrinsic anti-Cryptosporidium defense.

Intestinal epithelial cells possess the requisite molecular machinery to initiate cell-intrinsic defensive responses against intracellular pathogens, including intracellular parasites. Interferons(IFNs) have been identified as cornerstones of epithelial cell-intrinsic defense against such pathogens in the gastrointestinal tract. Long non-coding RNAs (lncRNAs) are RNA transcripts (>200 nt) not translated into protein and represent a critical regulatory component of mucosal defense. We report here that lncRNA Nostrill facilitates IFN-γ-stimulated intestinal epithelial cell-intrinsic defense against infection by Cryptosporidium, an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children. Nostrill promotes transcription of a panel of genes controlled by IFN-γ through facilitating Stat1 chromatin recruitment and thus, enhances expression of several genes associated with cell-intrinsic defense in intestinal epithelial cells in response to IFN-γ stimulation, including Igtp, iNos, and Gadd45g. Induction of Nostrill enhances IFN-γ-stimulated intestinal epithelial defense against Cryptosporidium infection, which is associated with an enhanced autophagy in intestinal epithelial cells. Our findings reveal that Nostrill enhances the transcription of a set of genes regulated by IFN-γ in intestinal epithelial cells. Moreover, induction of Nostrill facilitates the IFN-γ-mediated epithelial cell-intrinsic defense against cryptosporidial infections.

Bibliometric analysis of T-cells immunity in pulmonary hypertension from 1992 to 2022.

BACKGROUND: Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T-cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T-cells research in PH pathogenesis and to lay a solid foundation for further studies. METHODS: The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords. RESULTS: Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that "Pulmonary hypertension" was the most usually appeared keyword in the relevant literature, and included "T-cells", "Regulatory T cells", and "Activated T cell." "miRNA" of reference co-citation clustering analysis demonstrated the possible T-cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is "gene expression" and terms such as "vascular remodeling," "growth," "proliferation," and "fibrosis" are among the list, indicating that T-cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is "Galie N, 2016." CONCLUSIONS: T-cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T-cell immunity activation mechanisms in PH need to be investigated further.

Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease.

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis- regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.

Simulating Two-Phase Seepage in Undisturbed Soil Based on Lattice Boltzmann Method and X-ray Computed Tomography Images.

The two-phase seepage fluid (i.e., air and water) behaviors in undisturbed granite residual soil (U-GRS) have not been comprehensively studied due to a lack of accurate and representative models of its internal pore structure. By leveraging X-ray computed tomography (CT) along with the lattice Boltzmann method (LBM) enhanced by the Shan-Chen model, this study simulates the impact of internal pore characteristics of U-GRS on the water-gas two-phase seepage flow behaviors. Our findings reveal that the fluid demonstrates a preference for larger and straighter channels for seepage, and as seepage progresses, the volume fraction of the water/gas phases exhibits an initial increase/decrease trend, eventually stabilizing. The results show the dependence of two-phase seepage velocity on porosity, while the local seepage velocity is influenced by the distribution and complexity of the pore structure. This emphasizes the need to consider pore distribution and connectivity when studying two-phase flow in undisturbed soil. It is observed that the residual gas phase persists within the pore space, primarily localized at the pore margins and dead spaces. Furthermore, the study identifies that hydrophobic walls repel adjacent fluids, thereby accelerating fluid movement, whereas hydrophilic walls attract fluids, inducing a viscous effect that decelerates fluid flow. Consequently, the two-phase flow rate is found to increase with then-enhanced hydrophobicity. The apex of the water-phase volume fraction is observed under hydrophobic wall conditions, reaching up to 96.40%, with the residual gas-phase constituting 3.60%. The hydrophilic wall retains more residual gas-phase volume fraction than the neutral wall, followed by the hydrophobic wall. Conclusively, the investigations using X-ray CT and LBM demonstrate that the pore structure characteristics and the wettability of the pore walls significantly influence the two-phase seepage process.

Conjugation-Broken Dimer Acceptors Enable High-Efficiency, Stable, and Flexibility-Robust Organic Solar Cells.

Dimer acceptors in organic solar cells (OSCs) offer distinct advantages, including a well-defined molecular structure and excellent batch-to-batch reproducibility. Their high glass transition temperature (Tg) aids in achieving an optimal kinetic morphology, thereby enhancing device stability. Currently, most of dimer acceptor materials are linked with conjugated units in order to obtain high power conversion efficiencies (PCEs). In this study, different from previous works on conjugation-linked dimer acceptors, a novel series of dimer acceptors are synthesized (named T1, T4, T6, and T12), each linked with different flexible alkyl linkers, and investigated their PCEs, device stability, and flexibility robustness. When blended with PM6, the T6-based device achieves a PCE of 17.09%, comparable to the fully conjugated T0-based device's PCE of 17.12%. The molecular dynamics simulations and density functional theory calculations suggested that flexible conjugation-broken linkers (FCBLs) promote intermolecular electronic couplings, thereby maintaining good electron mobilities of dimer acceptors. Notably, the T6-based device exhibits impressive long-term stability with a T80 lifetime of 1427 h, while in the T0-based device, T80 is only 350 h. The present work has thus established the relationship between the length of flexible alkyl linkers in such dimer acceptors and the performance and stability of OSCs, which is important to further designing new materials for the fabrication of efficient and stable OSCs.

Mixture Theory-Based Finite Element Approach for Analyzing the Edematous Condition of Biological Soft Tissues.

In hydrated soft biological tissues experiencing edema, which is typically associated with various disorders, excessive fluid accumulates and is encapsulated by impermeable membranes. In certain cases of edema, an indentation induced by pressure persists even after the load is removed. The depth and duration of this indentation are used to assess the treatment response. This study presents a mixture theory-based approach to analyzing the edematous condition. The finite element analysis formulation was grounded in mixture theory, with the solid displacement, pore water pressure, and fluid relative velocity as the unknown variables. To ensure tangential fluid flow at the surface of tissues with complex shapes, we transformed the coordinates of the fluid velocity vector at each time step and node, allowing for the incorporation of the transmembrane component of fluid flow as a Dirichlet boundary condition. Using this proposed method, we successfully replicated the distinct behavior of pitting edema, which is characterized by a prolonged recovery time from indentation. Consequently, the proposed method offers valuable insights into the finite element analysis of the edematous condition in biological tissues.

Frenkel and Charge-Transfer Excitonic Couplings Strengthened by Thiophene-Type Solvent Enables Binary Organic Solar Cells with 19.8% Efficiency.

Overcoming the trade-off between short-circuited current (Jsc) and open-circuited voltage (Voc) is important to achieving high-efficiency organic solar cells (OSCs). Previous works modulated energy gap between Frenkel local exciton (LE) and charge-transfer (CT) exciton, which is served as driving force of exciton splitting. Differently, our current work focuses on modulation of LE-CT excitonic coupling (tLE-CT) via a simple but effective strategy that the 2-chlorothiophene (2Cl-Th) solvent is utilized in treatment of OSC active-layer films. The results of our experimental measurements and theoretical simulations demonstrated that 2Cl-Th solvent initiates the tighter intermolecular interactions with non-fullerene acceptor in comparison with that of traditional chlorobenzene solvent, thus suppressing the acceptor's over-aggregation and retarding the acceptor crystallization with reduced trap. Importantly, the resulted shorter distances between donor and acceptor molecules in the 2Cl-Th treated blend efficiently strengthen tLE-CT, which not only promotes the exciton splitting but also reduces non-radiative recombination. The champion efficiencies of 19.8% (small-area) with a superior operational reliability (T80: 586 hours) and 17.0% (large-area) were yielded in 2Cl-Th treated cells. This work provided a new insight into modulating the exciton dynamics to overcome the trade-off between Jsc and Voc, which can productively promote the development of OSC field.

Global burden and cross-country inequalities in stroke and subtypes attributable to diet from 1990 to 2019.

DATA SOURCES: The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. BACKGROUND: To describe burden, and to explore cross-country inequalities according to socio-demographic index (SDI) for stroke and subtypes attributable to diet. METHODS: Death and years lived with disability (YLDs) data and corresponding estimated annual percentage changes (EAPCs) were estimated by year, age, gender, location and SDI. Pearson correlation analysis was performed to evaluate the connections between age-standardized rates (ASRs) of death, YLDs, their EAPCs and SDI. We used ARIMA model to predict the trend. Slope index of inequality (SII) and relative concentration index (RCI) were utilized to quantify the distributive inequalities in the burden of stroke. RESULTS: A total of 1.74 million deaths (56.17% male) and 5.52 million YLDs (55.27% female) attributable to diet were included in the analysis in 2019.Between 1990 and 2019, the number of global stroke deaths and YLDs related to poor diet increased by 25.96% and 74.76% while ASRs for death and YLDs decreased by 42.29% and 11.34% respectively. The disease burden generally increased with age. The trends varied among stroke subtypes, with ischemic stroke (IS) being the primary cause of YLDs and intracerebral hemorrhage (ICH) being the leading cause of death. Mortality is inversely proportional to SDI (R = -0.45, p < 0.001). In terms of YLDs, countries with different SDIs exhibited no significant difference (p = 0.15), but the SII changed from 38.35 in 1990 to 45.18 in 2019 and the RCI showed 18.27 in 1990 and 24.98 in 2019 for stroke. The highest ASRs for death and YLDs appeared in Mongolia and Vanuatu while the lowest of them appeared in Israel and Belize, respectively. High sodium diets, high red meat consumption, and low fruit diets were the top three contributors to stroke YLDs in 2019. DISCUSSION: The burden of diet-related stroke and subtypes varied significantly concerning year, age, gender, location and SDI. Countries with higher SDIs exhibited a disproportionately greater burden of stroke and its subtypes in terms of YLDs, and these disparities were found to intensify over time. To reduce disease burden, it is critical to enforce improved dietary practices, with a special emphasis on mortality drop in lower SDI countries and incidence decline in higher SDI countries.

Tension Induced Photoluminescence Enhancement in an Organic Single Crystal.

Organic single crystals possess distinct advantages due to their highly ordered molecular structures, resulting in improved stability, enhanced carrier mobility, and superior optical characteristics. However, their mechanical rigidity and brittleness impede the applications in flexible and wearable optoelectronic devices. Here, photoluminescence (PL) emission from 2,6-diphenylanthracene (DPA) single crystals is studied under tensile strain, which shows PL enhancement by more than two times with a strain of ≈1.42%. Such a tension induced PL enhancement is reversible, exhibiting no clear optical degradations during 100 cycles of bending and recovery processes. Theoretical calculations reveal that the deformation of molecular structure under strain induces a decrease of the dihedral between anthracene and benzene moieties in DPA molecules. Further, the increased molecular conjugation enhances the molecular oscillator strength, leading to the brightened PL emission. Meanwhile, with the decreased dihedral, the molecular vibrations in DPA crystals are suppressed, which can reduce the non-radiative decay rate. In contrast, no tension induced PL enhancement is observed in polycrystalline DPA thin films as the strain can be released via the grain boundaries. This study highlights the superior optical performance of DPA single crystals under strain field, which will provide new possibilities for DPA-based flexible devices.

Electrochemical Behaviors and Doping Rules of NaRhO2 Cathode Materials for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have great advantages for energy storage and conversion due to their low cost and large storage capacity. Currently, NaRhO2 is used as an electrode material for sodium-ion batteries. Doping first- and second-row transition metals has been carried out to comprehensively assess NaRhO2 as a cathode material. The geometric and electronic structures and electrochemical and doping behaviors of NaRhO2 cathode materials for SIBs have been investigated using density functional theory calculations. The results show that the bond lengths of Rh-O in NaRhO2 decrease during sodium deintercalation. The band gap of NaRhO2 with sodium extraction gradually reduces. The density of states of NaxRhO2 shows that the interaction between the Rh-4d and O-2p orbitals increases and the orbitals shift toward the right. The average intercalation voltage of NaxRhO2 cathode material increased from 2.7 to 3.9 eV. After doping with first- and second-row transition metal elements from Sc to Zn and Y to Cd, the changes in the band gaps of the doped NaRhO2 materials exhibit a W-type rule. In contrast, their magnetic moments show a reverse W-type rule. These findings on the pristine and doped NaRhO2 can provide theoretical guidance for the preparation of novel electrode materials suitable for sodium-ion batteries.

Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process. METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice. RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet. CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.