Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Global transmission of broad-host-range plasmids derived from the human gut microbiome.

Broad-host-range (BHR) plasmids in human gut bacteria are of considerable interest for their ability to mediate horizontal gene transfer (HGT) across large phylogenetic distance. However, the human gut plasmids, especially the BHR plasmids, remain largely unknown. Here, we identified the plasmids in the draft genomes of gut bacterial isolates from Chinese and American donors, resulting in 5372 plasmid-like clusters (PLCs), of which, 820 PLCs (comPLCs) were estimated with > 60% completeness genomes and only 155 (18.9%) were classified to known replicon types (n = 37). We observed that 175 comPLCs had a broad host range across distinct bacterial genera, of which, 71 were detected in at least two human populations of Chinese, American, Spanish, and Danish, and 13 were highly prevalent (>10%) in at least one human population. Haplotype analyses of two widespread PLCs demonstrated their spreading and evolutionary trajectory, suggesting frequent and recent exchanges of the BHR plasmids in environments. In conclusion, we obtained a large collection of plasmid sequences in human gut bacteria and demonstrated that a subset of the BHR plasmids can be transmitted globally, thus facilitating extensive HGT (e.g. antibiotic resistance genes) events. This study highlights the potential implications of the plasmids for global human health.

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

Ultra-Stable Ti Vacancies-Pt Atomic Clusters Structure on Titanium Oxycarbide Supports for High Current Density Hydrogen Evolution Reaction.

Electrocatalysts with low Pt loading mass to achieve high current density (≥1 A cm-2) for hydrogen evolution reaction (HER) are still extremely challenging due to the limited intrinsic activity and weak stability of catalytic sites. The modulation of the electronic microenvironment of the support-Pt structure is crucial to enhance the intrinsic activity and stability of catalytic sites. Herein, an innovative titanium oxycarbide (TiVCO) solid solution with Ti vacancies (TiV) is proposed as support to anchor sub-nanoscale Pt atomic clusters (Pt ACs) and a stable "TiV-Pt ACs" structure is carefully designed. The electronic microenvironment of "TiV-Pt ACs" is indirectly optimized by an unsaturated C/O site near TiV. Thanks to this, novel "TiV-Pt ACs" structure (Pt@TiVCO) with low Pt loading mass (2.44 wt.%) exhibits excellent HER activity in acidic solution and the mass activity is more than ten times that of commercial 20% Pt/C at the overpotentials of 50 and 100 mV. Particularly, Pt@TiVCO shows amazing stability at high and fluctuating current density of 1-2 A cm-2 for 120 h. This work provides a novel and promising method to develop stable and low-loading Pt-based catalysts adapting to high current density.

Carbon Structure Regulation Strategy for the Electrode of Vanadium Redox Flow Battery.

Vanadium redox flow battery (VRFB) is a type of energy storage device known for its large-scale capacity, long-term durability, and high-level safety. It serves as an effective solution to address the instability and intermittency of renewable energy sources. Carbon-based materials are widely used as VRFB electrodes due to cost-effectiveness and well-stability. However, pristine electrodes need proper modification to overcome original poor hydrophilicity and fewer reaction active sites. Adjusting the carbon structure is recognized as a viable method to boost the electrochemical activity of electrodes. This review delves into the advancements in research related to ordered and disordered carbon structure electrodes including the adjusting methods, structural characteristics, and catalytic properties. Ordered carbon structures are categorized into nanoscale and macroscale orderliness based on size, leading to improved conductivity and overall performance of the electrode. Disordered carbon structures encompass methods such as doping atoms, grafting functional groups, and creating engineered holes to enhance active sites and hydrophilicity. Based on the current research findings on carbon electrode structures, this work puts forth some promising prospects for future feasibility.

Sterically Hindered Tetradentate [Pt(O

Described here are sterically hindered tetradentate [Pt(O^N^C^N)] emitters (Pt-1, Pt-2, and Pt-3) developed for stable and high-performance green phosphorescent organic light-emitting diodes (OLEDs). These Pt(II) emitters exhibit strong saturated green phosphorescence (λmax = 517-531 nm) in toluene and mCP thin films with emission quantum yields as high as 0.97, radiative rate constants (kr) as high as 4.4-5.3 × 105 s-1 and reduced excimer emission, and with a preferential horizontally oriented transition dipole ratio of up to 84%. Theoretical calculations show that p-(hetero)arene substituents at the periphery of the ligand scaffolds in Pt-1, Pt-2, and Pt-3 can i) enhance the spin-orbit coupling (SOC) between the lower singlet excited states and the T1 state, and S0→Sn (n = 1 or 2) transition dipole moment, and ii) introducing additional SOC activity and the bright 1ILCT[π(carbazole)→π*(N^C^N)] excited state (Pt-2 and Pt-3), which are the main contributors to the increased kr values. Utilizing these tetradentate Pt(II) emitters, green phosphorescent OLEDs are fabricated with narrow-band electroluminescence (FWHM down to 36 nm), high external quantum efficiency, current efficiency up to 27.6% and 98.7 cd A-1, and an unprecedented device lifetime (LT95) of up to 9270 h at 1000 cd m-2 under laboratory conditions.

Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis.

BACKGROUND: Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. METHODS: Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. RESULTS: Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. CONCLUSIONS: Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics.

A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.

Mesoporous Metal Nanomaterials: Developments and Electrocatalytic Applications.

Mesoporous metal nanomaterials (MPMNs) are pivotal in nanotechnology, especially in electrochemical applications, due to their unique structure. Unlike traditional nanomaterials, MPMNs possess hierarchical and mesoporous characteristics, providing more active sites for improved mass and electron transfer. This distinctive composition offers dual benefits, enhancing activity, stability, and selectivity for specific reactions. The intricate architecture, featuring interconnected pores, amplifies surface area, ensuring efficient use of active sites and boosting reactivity in electrocatalytic processes. Additionally, the mesoporous nature promotes superior diffusion kinetics, facilitating better transport of reactants and products. This intricate interplay of structural elements contributes not only to the increased efficiency of electrochemical reactions but also to the extended durability of MPMNs during prolonged usage. This concept focus on the synthesis and design strategies of MPMNs, aligning with the dynamic requirements of diverse electrocatalytic applications. The synergy resulting from these advancements not only accentuates the intrinsic properties of MPMNs but also broadens their scope for practical implementation in emerging fields of electrochemistry.

Cancer-associated fibroblasts mediate resistance to anti-EGFR therapies in cancer.

Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.

Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.

BACKGROUND: A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear. METHODS: We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs). RESULTS: One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004-1.017, p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005-1.026, p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002-1.011, p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001-1.014, p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010, p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004-1.535, p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028-1.288, p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers. CONCLUSIONS: Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.

A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer.

BACKGROUND: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. METHODS: In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. RESULTS: Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. CONCLUSION: Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor.

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.

Origin differentiation based on volatile constituents of genuine medicinal materials Quisqualis indica L. via HS-GC-MS, response surface methodology, and chemometrics.

INTRODUCTION: Quisqualis indica L. (QIL) has a long history as a traditional Chinese herb in China, but the study of volatile components in QIL from different geographical sources has been relatively rare. OBJECTIVES: To establish an optimal headspace gas chromatography-mass spectrometry (HS-GC-MS) method to comprehensively analyse the volatile component profile and screen quality markers of QIL from different origins. METHODS: Response surface methodology (RSM) was used to optimise the conditions for headspace analysis. The volatile components of QIL from four main origins of southwest China were analysed and identified by HS-GC-MS. The similarity of all samples of QIL was evaluated by fingerprint. The differences of the volatile components in QIL from different origins were distinguished by chemometrics. RESULTS: According to the optimal conditions of RSM, a total of 31 volatile components were identified, including fatty acids, aldehydes, alcohols, alkyl pyrazines, and other volatile components. Similarity evaluation presented that there were 26 common volatile components with different contents in all samples. Principal component analysis (PCA) showed that QIL from four different origins could be roughly divided into four categories. Hierarchical cluster analysis (HCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) indicated that QIL from different origins had obvious regional characteristics. CONCLUSION: The optimised HS-GC-MS method provided a strategy to rapidly, effectively, and accurately elucidate the volatile component profile of QIL from different origins, and seven important differential components were screened for quality evaluation and origin traceability.

p-d Orbital Hybridization in Ag-based Electrocatalysts for Enhanced Nitrate-to-Ammonia Conversion.

Considering the substantial role of ammonia, developing highly efficient electrocatalysts for nitrate-to-ammonia conversion has attracted increasing interest. Herein, we proposed a feasible strategy of p-d orbital hybridization via doping p-block metals in an Ag host, which drastically promotes the performance of nitrate adsorption and disassociation. Typically, a Sn-doped Ag catalyst (SnAg) delivers a maximum Faradaic efficiency (FE) of 95.5 ± 1.85 % for NH3 at -0.4 V vs. RHE and reaches the highest NH3 yield rate to 482.3 ± 14.1 mg h-1 mgcat.-1. In a flow cell, the SnAg catalyst achieves a FE of 90.2 % at an ampere-level current density of 1.1 A cm-2 with an NH3 yield of 78.6 mg h-1 cm-2, during which NH3 can be further extracted to prepare struvite as high-quality fertilizer. A mechanistic study reveals that a strong p-d orbital hybridization effect in SnAg is beneficial for nitrite deoxygenation, a rate-determining step for NH3 synthesis, which as a general principle, can be further extended to Bi- and In-doped Ag catalysts. Moreover, when integrated into a Zn-nitrate battery, such a SnAg cathode contributes to a superior energy density of 639 Wh L-1, high power density of 18.1 mW cm-2, and continuous NH3 production.

ERK/RSK-mediated phosphorylation of Y-box binding protein-1 aggravates diabetic cardiomyopathy by suppressing its interaction with deubiquitinase OTUB1.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes, but its underlying mechanisms still remain unclear. The multifunctional protein Y-box binding protein-1 (YB-1) plays an important role in cardiac pathogenesis by regulating cardiac apoptosis, cardiac fibrosis, and pathological remodeling, whereas its role in chronic DCM requires further investigation. Here, we report that the phosphorylation of YB-1 at serine102 (S102) was markedly elevated in streptozotocin-induced diabetic mouse hearts and in high glucose-treated cardiomyocytes, whereas total YB-1 protein levels were significantly reduced. Coimmunoprecipitation experiments showed that YB-1 interacts with the deubiquitinase otubain-1, but hyperglycemia-induced phosphorylation of YB-1 at S102 diminished this homeostatic interaction, resulting in ubiquitination and degradation of YB-1. Mechanistically, the high glucose-induced phosphorylation of YB-1 at S102 is dependent on the upstream extracellular signal-regulated kinase (ERK)/Ras/mitogen-activated protein kinase (p90 ribosomal S6 kinase [RSK]) signaling pathway. Accordingly, pharmacological inhibition of the ERK pathway using the upstream kinase inhibitor U0126 ameliorated features of DCM compared with vehicle-treated diabetic mice. We demonstrate that ERK inhibition with U0126 also suppressed the phosphorylation of the downstream RSK and YB-1 (S102), which stabilized the interaction between YB-1 and otubain-1 and thereby preserved YB-1 protein expression in diabetic hearts. Taken together, we propose that targeting the ERK/RSK/YB-1 pathway could be a potential therapeutic approach for treating DCM.

Stabilizing Zn Metal Anode Through Regulation of Zn Ion Transfer and Interfacial Behavior with a Fast Ion Conductor Protective Layer.

Aqueous Zn-ion batteries (AZIBs) attract intensive attention owing to their environmental friendliness, cost-effectiveness, innate safety, and high specific capacity. However, the practical applications of AZIBs are hindered by several adverse phenomena, including corrosion, Zn dendrites, and hydrogen evolution. Herein, a Zn anode decorated with a 3D porous-structured Na3 V2 (PO4)3 (NVP@Zn) is obtained, where the NVP reconstruct the electrolyte/anode interface. The resulting NVP@Zn anode can provide a large quantity of fast and stable channels, facilitating enhanced Zn ion deposition kinetics and regulating the Zn ions transport process through the ion confinement effect. The NASICON-type NVP protective layer promote the desolvation process due to its nanopore structure, thus effectively avoiding side reactions. Theoretical calculations indicate that the NVP@Zn electrode has a higher Zn ion binding energy and a higher migration barrier, which demonstrates that NVP protective layer can enhance Zn ion deposition kinetics and prevent the unfettered 2D diffusion of Zn ions. Therefore, the results show that NVP@Zn/MnO2 full cell can maintain a high specific discharge capacity of 168 mAh g-1 and a high-capacity retention rate of 74.6% after cycling. The extraordinary results obtained with this strategy have confirmed the promising applications of NVP in high-performance AZIBs.

Zinc-Bismuth Binary Alloy Enabling High-Performance Aqueous Zinc Ion Batteries.

Reconfiguration of zinc anodes efficiently mitigates dendrite formation and undesirable side reactions, thus favoring the long-term cycling performance of aqueous zinc ion batteries (AZIBs). This study synthesizes a Zn@Bi alloy anode (Zn@Bi) using the fusion method, and find that the anode surfaces synthesized using this method have an extremely high percentage of Zn(002) crystalline surfaces. Experimental results indicate that the addition of bismuth inhibits the hydrogen evolution reaction and corrosion of zinc anodes. The finite-element simulation results indicate that Zn@Bi can effectively achieve a uniform anodic electric field, thereby regulating the homogeneous depositions of zinc ions and reducing the production of Zn dendrite. Theoretical calculations reveal that the incorporation of Bi favors the anode structure stabilization and higher adsorption energy of Zn@Bi corresponds to better Zn deposition kinetics. The Zn@Bi//Zn@Bi symmetric cell demonstrates an extended cycle life of 1000 h. Furthermore, when pairing Zn@Bi with an α-MnO2 cathode to construct a Zn@Bi//MnO2 cell, a specific capacity of 119.3 mAh g-1 is maintained even after 1700 cycles at 1.2 A g-1 . This study sheds light on the development of dendrite-free anodes for advanced AZIBs.

ONX0914 inhibition of immunoproteasome subunit LMP7 ameliorates diabetic cardiomyopathy via restraining endothelial-mesenchymal transition.

Diabetic cardiomyopathy (DCM) is a chronic metabolic disease with few effective therapeutic options. Immunoproteasome is an inducible proteasome that plays an important role in the regulation of many cardiovascular diseases, while its role in DCM remains under discussion. The present study aims to demonstrate whether inhibiting immunoproteasome subunit low molecular weight polypeptide 7 (LMP7) could alleviate DCM. Here, we established a type I diabetes mellitus mouse model by streptozotocin (STZ) in 8-week-old male wild-type C57BL/6J mice. We found that immunoproteasome subunit LMP7 was overexpressed in the heart of diabetic mice, while inhibiting LMP7 with pharmacological inhibitor ONX0914 significantly alleviated myocardial fibrosis and improved cardiac function. Besides, compared with diabetic mice, ONX0914 treatment reduced protein levels of mesenchymal markers (Vimentin, α-smooth muscle actin, and SM22α) and increased endothelial markers (VE-cadherin and CD31). In TGFß1 stimulated HUVECs, we also observed that ONX0914 could inhibit endothelial-mesenchymal transition (EndMT). Mechanistically, we prove that ONX0914 could regulate autophagy activity both in vivo and vitro. Meanwhile, the protective effect of ONX0914 on TGFß1 stimulated HUVECs could be abolished by 3-methyladenine (3MA) or hydroxychloroquine (CQ). All in all, our data highlight that inhibition of LMP7 with ONX0914 could ameliorate EndMT in diabetic mouse hearts at least in part via autophagy activation. Thus, LMP7 may be a potential therapeutic target for the DCM.

Profiling of d-alanine production by the microbial isolates of rat gut microbiota.

d-alanine (d-Ala) and several other d-amino acids (d-AAs) act as hormones and neuromodulators in nervous and endocrine systems. Unlike the endogenously synthesized d-serine in animals, d-Ala may be from exogenous sources, e.g., diet and intestinal microorganisms. However, it is unclear if the capability to produce d-Ala and other d-AAs varies among different microbial strains in the gut. We isolated individual microorganisms of rat gut microbiota and profiled their d-AA production in vitro, focusing on d-Ala. Serial dilutions of intestinal contents from adult male rats were plated on agar to obtain clonal cultures. Using MALDI-TOF MS for rapid strain typing, we identified 38 unique isolates, grouped into 11 species based on 16S rRNA gene sequences. We then used two-tier screening to profile bacterial d-AA production, combining a d-amino acid oxidase-based enzymatic assay for rapid assessment of non-acidic d-AA amount and chiral LC-MS/MS to quantify individual d-AAs, revealing 19 out of the 38 isolated strains as d-AA producers. LC-MS/MS analysis of the eight top d-AA producers showed high levels of d-Ala in all strains tested, with substantial inter- and intra-species variations. Though results from the enzymatic assay and LC-MS/MS analysis aligned well, LC-MS/MS further revealed the existence of d-glutamate and d-aspartate, which are poor substrates for this enzymatic assay. We observed large inter- and intra-species variation of d-AA production profiles from rat gut microbiome species, demonstrating the importance of chemical profiling of gut microbiota in addition to sequencing, furthering the idea that microbial metabolites modulate host physiology.