Separating water isotopologues using diffusion-regulatory porous materials.

The discovery of a method to separate isotopologues, molecular entities that differ in only isotopic composition1, is fundamentally and technologically essential but remains challenging2,3. Water isotopologues, which are very important in biological processes, industry, medical care, etc. are among the most difficult isotopologue pairs to separate because of their very similar physicochemical properties and chemical exchange equilibrium. Herein, we report efficient separation of water isotopologues at room temperature by constructing two porous coordination polymers (PCPs, or metal-organic frameworks) in which flip-flop molecular motions within the frameworks provide diffusion-regulatory functionality. Guest traffic is regulated by the local motions of dynamic gates on contracted pore apertures, thereby amplifying the slight differences in the diffusion rates of water isotopologues. Significant temperature-responsive adsorption occurs on both PCPs: H2O vapour is preferentially adsorbed into the PCPs, with substantially increased uptake compared to that of D2O vapour, facilitating kinetics-based vapour separation of H2O/HDO/D2O ternary mixtures with high H2O separation factors of around 210 at room temperature.

PredLLPS_PSSM: a novel predictor for liquid-liquid protein separation identification based on evolutionary information and a deep neural network.

The formation of biomolecular condensates by liquid-liquid phase separation (LLPS) has become a universal mechanism for spatiotemporal coordination of biological activities in cells and has been widely observed to directly regulate the key cellular processes involved in cancer cell pathology. However, the complexity of protein sequences and the diversity of conformations are inherently disordered, which poses great challenges for LLPS protein calculations and experimental research. Herein, we proposed a novel predictor named PredLLPS_PSSM for LLPS protein identification based only on sequence evolution information. Because finding real and reliable samples is the cornerstone of building predictors, we collected anew and collated the LLPS proteins from the latest versions of three databases. By comparing the performance of the position-specific score matrix (PSSM) and word embedding, PredLLPS_PSSM combined PSSM-based information and two deep learning frameworks. Independent tests using three existing independent test datasets and two newly constructed independent test datasets demonstrated the superiority of PredLLPS_PSSM compared with state-of-the-art methods. Furthermore, we tested PredLLPS_PSSM on nine experimentally identified LLPS proteins from three insects that were not included in any of the databases. In addition, the powerful Shapley Additive exPlanation algorithm and heatmap were applied to find the most critical amino acids relevant to LLPS.

N-GlycoPred: A hybrid deep learning model for accurate identification of N-glycosylation sites.

Studies have shown that protein glycosylation in cells reflects the real-time dynamics of biological processes, and the occurrence and development of many diseases are closely related to protein glycosylation. Abnormal protein glycosylation can be used as a potential diagnostic and prognostic marker of a disease, as well as a therapeutic target and a new breakthrough point for exploring pathogenesis. To address the issue of significant differences in the prediction results of previous models for different species, we constructed a hybrid deep learning model N-GlycoPred on the basis of dual-layer convolution, a paired attention mechanism and BiLSTM for accurate identification of N-glycosylation sites. By adopting one-hot encoding or the AAindex, we specifically selected the optimum combination of features and deep learning frameworks for human and mouse to refine the models. Based on six independent test datasets, our N-GlycoPred model achieved an average AUC of 0.9553, which is 0.23% higher than MusiteDeep. The comparison results indicate that our model can serve as a powerful tool for N-glycosylation site prescreening for biological researchers.

Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons with HIV Receiving Tenofovir Alafenamide and Emtricitabine-based Antiretroviral Therapy (QUANTI-TAF).

BACKGROUND: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). METHODS: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. RESULTS: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). CONCLUSIONS: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

Enzyme-Driven LC-HRMS Approach for Specific Recognition of 12α-Hydroxy Bile Acids.

The synthesis of 12α-hydroxylated bile acids (12HBAs) and non-12α-hydroxylated bile acids (non-12HBAs) occurs via classical and alternative pathways, respectively. The composition of these BAs is a crucial index for pathophysiologic assessment. However, accurately differentiating 12HBAs and non-12HBAs is highly challenging due to the limited standard substances. Here, we innovatively introduce 12α-hydroxysteroid dehydrogenase (12α-HSDH) as an enzymatic probe synthesized by heterologous expression in Escherichia coli, which can specifically and efficiently convert 12HBAs in vitro under mild conditions. Coupled to the conversion rate determined by liquid chromatography-high resolution mass spectrometry (LC-HRMS), this enzymatic probe allows for the straightforward distinguishing of 210 12HBAs and 312 non-12HBAs from complex biological matrices, resulting in a BAs profile with a well-defined hydroxyl feature at the C12 site. Notably, this enzyme-driven LC-HRMS approach can be extended to any molecule with explicit knowledge of enzymatic transformation. We demonstrate the practicality of this BAs profile in terms of both revealing cross-species BAs heterogeneity and monitoring the alterations of 12HBAs and non-12HBAs under asthma disease. We envisage that this work will provide a novel pattern to recognize the shift of BA metabolism from classical to alternative synthesis pathways in different pathophysiological states, thereby offering valuable insights into the management of related diseases.

Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

Arbitrary fabrication of complex lithium niobate three-dimensional microstructures for second harmonic generation enhancement.

Lithium niobate (LN) crystal plays important roles in future integrated photonics, but it is still a great challenge to efficiently fabricate three-dimensional micro-/nanostructures on it. Here, a femtosecond laser direct writing-assisted liquid back-etching technology (FsLDW-LBE) is proposed to achieve the three-dimensional (3D) microfabrication of lithium niobate (LN) with high surface quality (Ra = 0.422 nm). Various 3D structures, such as snowflakes, graphic arrays, criss-cross arrays, and helix arrays, have been successfully fabricated on the surface of LN crystals. As an example, a microcone array was fabricated on LN crystals, which showed a strong second harmonic signal enhancement with up to 12 times bigger than the flat lithium niobate. The results indicate that the method provides a new approach for the microfabrication of lithium niobate crystals for nonlinear optics.

The Effect of Conformational Freedom vs Restriction on the Rate in Asymmetric Hydrogenation: Iridium-Catalyzed Regio- and Enantioselective Monohydrogenation of Dienones.

Transition metal-catalyzed asymmetric hydrogenation constitutes an efficient strategy for the preparation of chiral molecules. When dienes are subjected to hydrogenation, control over regioselectivity still presents a large challenge and the fully saturated alkane is often yielded. A few successful monohydrogenations of dienes have been reported, but hitherto these are only efficient for dienes comprised of two distinctly different olefins. Herein, the reactivity of a conjugated carbonyl compound as a function of their conformational freedom is studied, based on a combined experimental and theoretical approach. It was found that alkenes in the (s)-cis conformation experience a large rate acceleration while (s)-trans restrained alkenes undergo hydrogenation slowly. Ultimately, this reactivity aspect was exploited in a novel method for the monohydrogenation of dienes based on conformational restriction ((s)-cis vs (s)-trans). This mode of discrimination conceptually differs from existing monohydrogenations and dienones constructed of two olefins similar in nature could efficiently be hydrogenated to the chiral alkene (up to 99 % ee). The extent of regioselection is even powerful enough to overcome the conventional reactivity order of substituted olefins (di>tri>tetra). This high yielding and atom-economical protocol provides an interesting opportunity to instal a stereogenic center on a carbocycle, while leaving a synthetically useful alkene untouched.

Identification of antimicrobial peptide genes from transcriptomes in Mandarin fish (Siniperca chuatsi) and their response to infection with Aeromonas hydrophila.

Mandarin fish (Siniperca chuatsi) is a valuable freshwater fish species widely cultured in China. Its aquaculture production is challenged by bacterial septicaemia, which is one of the most common bacterial diseases. Antimicrobial peptides (AMPs) play a critical role in the innate immune system of fish, exhibiting defensive and inhibitory effects against a wide range of pathogens. This study aimed to identify the antimicrobial peptide genes in mandarin fish using transcriptomes data obtained from 17 tissue in our laboratory. Through nucleotide sequence alignment and protein structural domain analysis, 15 antimicrobial peptide genes (moronecidin, pleurocidin, lysozyme g, thymosin ß12, hepcidin, leap 2, ß-defensin, galectin 8, galectin 9, apoB, apoD, apoE, apoF, apoM, and nk-lysin) were identified, of which 9 antimicrobial peptide genes were identified for the first time. In addition, 15 AMPs were subjected to sequence characterization and protein structure analysis. After injection with Aeromonas hydrophila, the number of red blood cells, hemoglobin concentration, and platelet counts in mandarin fish showed a decreasing trend, indicating partial hemolysis. The expression change patterns of 15 AMP genes in the intestine after A. hydrophila infection were examined by using qRT-PCR. The results revealed, marked up-regulation (approximately 116.04) of the hepcidin gene, down-regulation of the piscidin family genes expression. Moreover, most AMP genes were responded in the early stages after A. hydrophila challenge. This study provides fundamental information for investigating the role of the different antimicrobial peptide genes in mandarin fish in defense against A. hydrophila infection.

AMPpred-MFA: An Interpretable Antimicrobial Peptide Predictor with a Stacking Architecture, Multiple Features, and Multihead Attention.

Antimicrobial peptides (AMPs) are small molecular polypeptides that can be widely used in the prevention and treatment of microbial infections. Although many computational models have been proposed to help identify AMPs, a high-performance and interpretable model is still lacking. In this study, new benchmark data sets are collected and processed, and a stacking deep architecture named AMPpred-MFA is carefully designed to discover and identify AMPs. Multiple features and a multihead attention mechanism are utilized on the basis of a bidirectional long short-term memory (LSTM) network and a convolutional neural network (CNN). The effectiveness of AMPpred-MFA is verified through five independent tests conducted in batches. Experimental results show that AMPpred-MFA achieves a state-of-the-art performance. The visualization interpretability analyses and ablation experiments offer a further understanding of the model behavior and performance, validating the importance of our feature representation and stacking architecture, especially the multihead attention mechanism. Therefore, AMPpred-MFA can be considered a reliable and efficient approach to understanding and predicting AMPs.

Zbtb46 Controls Dendritic Cell Activation by Reprogramming Epigenetic Regulation of cd80/86 and cd40 Costimulatory Signals in a Zebrafish Model.

The establishment of an appropriate costimulatory phenotype is crucial for dendritic cells (DCs) to maintain a homeostatic state with optimal immune surveillance and immunogenic activities. The upregulation of CD80/86 and CD40 is a hallmark costimulatory phenotypic switch of DCs from a steady state to an activated one for T cell activation. However, knowledge of the regulatory mechanisms underlying this process remains limited. In this study, we identified a Zbtb46 homolog from a zebrafish model. Zbtb46 deficiency resulted in upregulated cd80/86 and cd40 expression in kidney marrow-derived DCs (KMDCs) of zebrafish, which was accompanied with a remarkable expansion of CD4+/CD8+ T cells and accumulation of KMDCs in spleen of naive fish. Zbtb46 -/- splenic KMDCs exhibited strong stimulatory activity for CD4+ T cell activation. Chromatin immunoprecipitation-quantitative PCR and mass spectrometry assays showed that Zbtb46 was associated with promoters of cd80/86 and cd40 genes by binding to a 5'-TGACGT-3' motif in resting KMDCs, wherein it helped establish a repressive histone epigenetic modification pattern (H3K4me0/H3K9me3/H3K27me3) by organizing Mdb3/organizing nucleosome remodeling and deacetylase and Hdac3/nuclear receptor corepressor 1 corepressor complexes through the recruitment of Hdac1/2 and Hdac3. On stimulation with infection signs, Zbtb46 disassociated from the promoters via E3 ubiquitin ligase Cullin1/Fbxw11-mediated degradation, and this reaction can be triggered by the TLR9 signaling pathway. Thereafter, cd80/86 and cd40 promoters underwent epigenetic reprogramming from the repressed histone modification pattern to an activated pattern (H3K4me3/H3K9ac/H3K27ac), leading to cd80/86 and cd40 expression and DC activation. These findings revealed the essential role of Zbtb46 in maintaining DC homeostasis by suppressing cd80/86 and cd40 expression through epigenetic mechanisms.

Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium.

AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

The role of TRPV ion channels in adipocyte differentiation: What is the evidence?

Obesity is a complex disorder, and the incidence of obesity continues to rise at an alarming rate worldwide. In particular, the growing incidence of overweight and obesity in children is a major health concern. However, the underlying mechanisms of obesity remain unclear and the efficacy of several approaches for weight loss is limited. As an important calcium-permeable temperature-sensitive cation channel, transient receptor potential vanilloid (TRPV) ion channels directly participate in thermo-, mechano-, and chemosensory responses. Modulation of TRPV ion channel activity can alter the physiological function of the ion channel, leading to neurodegenerative diseases, chronic pain, cancer, and skin disorders. In recent years, increasing studies have demonstrated that TRPV ion channels are abundantly expressed in metabolic organs, including the liver, adipose tissue, skeletal muscle, pancreas, and central nervous system, which has been implicated in various metabolic diseases, including obesity and diabetes mellitus. In addition, as an important process for the pathophysiology of adipocyte metabolism, adipocyte differentiation plays a critical role in obesity. In this review, we focus on the role of TRPV ion channels in adipocyte differentiation to broaden the ideas for prevention and control strategies for obesity.

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.

Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis-angiogenesis coupling of BMSCs via the Wnt/ß-catenin pathway.

Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy-induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up-regulated the expression of angiogenic-related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/ß-catenin pathway. Subsequently, using ovariectomy-induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis-angiogenesis coupling of BMSCs via the Wnt/ß-catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.

"Adjacent Bed Effect" of Total Knee Arthroplasty Patients During the Perioperative Period.

BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.

Role of CCRL2 in the Pathogenesis of Experimental Autoimmune Myocarditis via P21-Activated Kinase 1/NOD-Like Receptor Protein 3 Pathway.

Myocarditis, a severe inflammatory disease, is becoming a worldwide public health concern. This study aims to elucidate the effect of Chemokine (C C motif) receptor-like 2 (CCRL2) in experimental autoimmune myocarditis (EAM) occurrence and its potential regulatory mechanisms.EAM was simulated in a mouse model injected with α-myosin-heavy chain. The changes on EAM were assessed through histological staining of heart tissues, including measuring cardiac troponin I (cTnI), proinflammatory cytokines, transferase-mediated dUTP nick end labeling (TUNEL) assay, and cardiac function. Then, the heart tissues from the EAM mouse model and control groups were analyzed through transcriptome sequencing to identify the differential expressed genes (DEGs) and hub genes related to pyroptosis. Downregulation of CCRL2 further verified the function of CCRL2 on EAM and p21-activated kinase 1/NOD-like receptor protein 3 (PAK/NLRP3) signaling pathways in vivo.The EAM model was constructed successfully, with the heart weight/body weight ratio, serum level of cTnI, and concentrations of proinflammatory cytokines elevation. Moreover, cell apoptosis was also significantly increased. Transcriptome sequencing revealed 696 and 120 upregulated and downregulated DEGs, respectively. After functional enrichment, CCRL2 was selected as a potential target. Then, we verified that CCRL2 knockdown improved cardiac function, alleviated EAM occurrence, and reduced PAK/NLRP3 protein expression.CCRL2 may act as a novel potential treatment target in EAM by regulating the PAK1/NLRP3 pathway.

Wuliangye strong aroma baijiu promotes intestinal homeostasis by improving gut microbiota and regulating intestinal stem cell proliferation and differentiation.

BACKGROUND: Wuliangye strong aroma baijiu (hereafter, Wuliangye baijiu) is a traditional Chinese grain liquor containing short-chain fatty acids, ethyl caproate, ethyl lactate, other trace components, and a large proportion of ethanol. The effects of Wuliangye baijiu on intestinal stem cells and intestinal epithelial development have not been elucidated. Here, the role of Wuliangye baijiu in intestinal epithelial regeneration and gut microbiota modulation was investigated by administering a Lieber-DeCarli chronic ethanol liquid diet in a mouse model to mimic long-term (8 weeks') light/moderate alcohol consumption (1.6 g kg-1 day-1) in healthy human adults. RESULTS: Wuliangye baijiu promoted colonic crypt proliferation in mice. According to immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses, compared with the ethanol-only treatment, Wuliangye baijiu increased the number of intestinal stem cells and goblet cells and the expression of enteroendocrine cell differentiation markers in the mouse colon. Furthermore, gut microbiota analysis showed an increase in the relative abundance of microbiota related to intestinal homeostasis following Wuliangye baijiu administration. Notably, increased abundance of Bacteroidota, Faecalibaculum, Lachnospiraceae, and Blautia may play an essential role in promoting stem-cell-mediated intestinal epithelial development and maintaining intestinal homeostasis. CONCLUSIONS: In summary, these findings suggest that Wuliangye baijiu can be used to regulate intestinal stem cell proliferation and differentiation in mice and to alter gut microbiota distributions, thereby promoting intestinal homeostasis. This research elucidates the mechanism by which Wuliangye baijiu promotes intestinal health. © 2024 Society of Chemical Industry.

Modular Design of Highly Stable Semiconducting Porous Coordination Polymer for Efficient Electrosynthesis of Ammonia.

Developing highly stable porous coordination polymers (PCPs) with integrated electrical conductivity is crucial for advancing our understanding of electrocatalytic mechanisms and the structure-activity relationship of electrocatalysts. However, achieving this goal remains a formidable challenge because of the electrochemical instability observed in most PCPs. Herein, we develop a "modular design" strategy to construct electrochemically stable semiconducting PCP, namely, Fe-pyNDI, which incorporates a chain-type Fe-pyrazole metal cluster and π-stacking column with effective synergistic effects. The three-dimensional electron diffraction (3D ED) technique resolves the precise structure. Both theoretical and experimental investigation confirms that the π-stacking column in Fe-pyNDI can provide an efficient electron transport path and enhance the structural stability of the material. As a result, Fe-pyNDI can serve as an efficient model electrocatalyst for nitrate reduction reaction (NO3RR) to ammonia with a superior ammonia yield of 339.2 µmol h-1 cm-2 (14677 µg h-1 mgcat. -1) and a faradaic efficiency of 87 % at neutral electrolyte, which is comparable to state-of-the-art electrocatalysts. The in-situ X-ray absorption spectroscopy (XAS) reveals that during the reaction, the structure of Fe-pyNDI can be kept, while part of the Fe3+ in Fe-pyNDI was reduced in situ to Fe2+, which serves as the potential active species for NO3RR.

Novel Stereo-Induction Pattern in Pudovik Addition/Phospha-Brook Rearrangement Towards Chiral Trisubstituted Allenes.

Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity of reports on axially chiral allenyl phosphorus compounds. Here, we disclosed an efficient and straightforward cascade reaction between ethynyl ketones and phosphine oxides, resulting in a broad array of trisubstituted allenes incorporating a phosphorus moiety in high yields with excellent stereoselectivities facilitated by peptide-mimic phosphonium salt (PPS) catalysis, Additionally, comprehensive series of mechanistic experiments have been conducted to elucidate that this cascade reaction proceeds via an asymmetric Pudovik addition reaction followed by a subsequent phospha-Brook rearrangement that occurs concomitantly with kinetic resolution, representing a stereospecific rearrangement and protonation process facilitating central-to-axial chirality transfer in a cascade manner. We anticipate that our research will pave the way for a promising exploration of novel stereo-induction pattern in the Pudovik addition/phospha-Brook rearrangement cascade reaction.