Valence band-tunable NiFe electrocatalyst triggered by the dynamic Mo exudation and re-deposition for superior high current density oxygen evolution reaction.

Developing energy- and time-efficient strategies to derive high-performance non-precious electrocatalysts for anodic oxygen evolution reaction (OER), especially stably working at industrial-demanding current density, is still a big challenge. In this work, a concise molten salt erosion scenario was devised to rapidly modulate the smooth surface of the commercial NiMo foam substrate into the rough, electronically coupled, and hierarchically porous Ni/Fe/Mo(oxy)hydroxide catalyst layer assembled by the nanosphere array. This self-supported catalyst is super-hydrophilic for the alkaline electrolyte and distinguished by a balanced Mo leaching/surface-readsorption process to tune the metal d band center and electronic perturbation. The altered electronic environment with the favored OER intermediate adsorption behavior attains the outstanding OER activity in terms of a very small overpotential of 230.21 mV at 10 mA cm-2 and an ultra-long stability for 1179.45 h to sustain the initial commercial-level current density of ca. 1000 mA cm-2. This superb performance transcends most of the edge-cutting transition metal peers reported recently and can satisfy the standards of industrial applications. This industrial-compatible synthesis technology holds profound implications for hydrogen production via water splitting and other electrochemical applications.

Reduced PTPRS expression promotes epithelial-mesenchymal transition of Schwann cells in NF1-related plexiform neurofibromas.

Plexiform neurofibromas (PNFs) are a prevalent and severe phenotype associated with NF1, characterized by a high teratogenic rate and potential for malignant transformation. The growth and recurrence of PNFs are attributed to aberrant proliferation and migration of Nf1-deficient Schwann cells. Protein tyrosine phosphatase receptor S (PTPRS) is believed to modulate cell migration and invasion by inhibiting the EMT process in NF1-derived malignant peripheral nerve sheath tumors. Nevertheless, the specific role of PTPRS in NF1-derived PNFs remains to be elucidated. The study utilized the GEO database and tissue microarray to illustrate a decrease in PTPRS expression in PNF tissues, linked to tumor recurrence. Furthermore, the down- and over-expression of PTPRS in Nf1-deficient Schwann cell lines resulted in the changes of cell migration and EMT processes. Additionally, RTK assay and WB showed that PTPRS knockdown can promote EGFR expression and phosphorylation. The restoration of EMT processes disrupted by alterations in PTPRS levels in Schwann cells can be achieved through EGFR knockdown and EGFR inhibitor. Moreover, high EGFR expression has been significantly correlated with poor prognosis. These findings underscore the potential role of PTPRS as a tumor suppressor in the recurrence of PNF via the regulation of EGFR-mediated EMT processes, suggesting potential targets for future clinical interventions.

Relationship between carotid atherosclerosis and lipoprotein (a) in patients with acute ischemic stroke.

Objective: This study aimed to examine the relationship between lipoprotein (a) (Lp[a]) and other blood lipid indexes and carotid artery atherosclerosis in patients with acute ischemic stroke (AIS). Methods: A total of 2,018 patients were selected from the hospital "acute stroke intervention and secondary prevention registration database" by identifying blood fat indexes (cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Lp[a]). Based on the results of carotid artery ultrasound examinations, the patients were divided into a "no plaque" group, comprising 400 patients, a "plaque and no stenosis" group, comprising 1,122 patients and a "carotid stenosis" group, comprising 496 patients. The relationship between Lp(a) and blood lipid indexes and carotid artery atherosclerosis was then investigated using multi-factor logistics regression analysis. Results: There were 400 patients (19.8%) with no carotid plaque, 1,122 patients (55.6%) with plaque and no carotid stenosis and 496 patients (24.6%) with carotid stenosis. As the degree of carotid artery atherosclerosis increased, the Lp(a) level gradually increased; Lp(a) and cholesterol were identified as independent risk factors for carotid atherosclerosis. Conclusion: Lipoprotein (a) and cholesterol are independent risk factors for patients with AIS with carotid atherosclerosis, and their levels increase with the degree of carotid artery atherosclerosis; therefore, attention should focus on levels of cholesterol and Lp(a) in acute stroke patients to control atherosclerosis effectively.

Cationic conjugated polymer coupled non-conjugated segments for dually enhanced NIR-II fluorescence and lower-temperature photothermal-gas therapy.

The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000-1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo.

Surface display of the COE antigen of porcine epidemic diarrhoea virus on Bacillus subtilis spores.

Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC-Linker-COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO-26 K equivalent (COE) of the epidemic strain PEDV-AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168-CLE, B. subtilis 168, or phosphate-buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL-4, IFN-γ) levels in the B. subtilis 168-CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168-CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.

Amomum villosum Lour.: An insight into ethnopharmacological, phytochemical, and pharmacological overview.

ETHNOPHARMACOLOGICAL RELEVANCE: Amomum villosum Lour. is a widely esteemed species of medicinal plant on a global scale. Its medicinal properties have been documented as early as the Tang Dynasty, particularly the fruit, which holds significant medicinal and culinary value. This plant is extensively found in tropical and subtropical regions across Asia. It possesses the properties of warming the middle and dispelling cold, regulating Qi to invigorate the spleen, harmonizing the stomach to alleviate vomiting, and nourishing deficiencies. In recent years, A. villosum has garnered global attention for its remarkable biological activity. Currently, numerous bioactive compounds have been successfully isolated and identified, showcasing a diverse array of pharmacological activities and medicinal benefits. AIM OF THE WORK: This review aims to provide a comprehensive analysis of the research advancements in the geographical distribution, botany, traditional applications, phytochemistry, pharmacological activity, quality control, clinical applications, and toxicology of A. villosum. Furthermore, a critical summary of the current research and future prospects of this plant is presented. MATERIALS AND METHODS: Obtain information about A. villosum from ancient literature, doctoral and master's theses, and scholarly databases including Google Scholar, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), ScienceDirect, plant directories, and clinical reports. RESULTS: At present, about 500 compounds have been isolated and identified from various organs of A. villosum, including monoterpenoids, sesquiterpenoids, diterpenoids, flavonoids, phenols, polysaccharides, and other components. Modern pharmacological studies have revealed that A. villosum exhibits exceptional biological activities in vitro and in vivo, such as anti-inflammatory, antioxidant, liver protection, anti-tumor, hypoglycemic, anti-microbial, regulating gastrointestinal activity, immune regulation, regulating flora, anti-obesity, estrogen, and more. Some of these activities have found extensive application in clinical practice. CONCLUSION: A. villosum, as a well-established medicinal herb, holds significant therapeutic potential and is also valued for its culinary applications. Currently, the research on the active components or crude extracts of A. villosum and their potential mechanisms of action remains limited. Furthermore, certain pharmacological activities require further elucidation for a comprehensive understanding of its internal mechanisms. Moreover, it is strongly recommended to prioritize research on pharmacokinetics and toxicity studies. These efforts will facilitate a thorough exploration of the potential of A. villosum and establish a robust foundation for its potential clinical applications.

Defect Passivation and Crystallization Regulation for Efficient and Stable Formamidinium Lead Iodide Solar Cells with Multifunctional Amidino Additive.

Amidino-based additives show great potential in high-performance perovskite solar cells (PSCs). However, the role of different functional groups in amidino-based additives have not been well elucidated. Herein, two multifunctional amidino additives 4-amidinobenzoic acid hydrochloride (ABAc) and 4-amidinobenzamide hydrochloride (ABAm) are employed to improve the film quality of formamidinium lead iodide (FAPbI3) perovskites. Compared with ABAc, the amide group imparts ABAm with larger dipole moment and thus stronger interactions with the perovskite components, i.e., the hydrogen bonds between N…H and I- anion and coordination bonds between C = O and Pb2+ cation. It strengthens the passivation effect of iodine vacancy defect and slows down the crystallization process of α-FAPbI3, resulting in the significantly reduced non-radiative recombination, long carrier lifetime of 1.7 µs, uniformly large crystalline grains, and enhances hydrophobicity. Profiting from the improved film quality, the ABAm-treated PSC achieves a high efficiency of 24.60%, and maintains 93% of the initial efficiency after storage in ambient environment for 1200 hours. This work provides new insights for rational design of multifunctional additives regarding of defect passivation and crystallization control toward highly efficient and stable PSCs.

Nanomaterials revolutionize biosensing: 0D-3D designs for ultrasensitive detection of microorganisms and viruses.

Various diseases caused by harmful microorganisms and viruses have caused serious harm and huge economic losses to society. Thus, rapid detection of harmful microorganisms and viruses is necessary for disease prevention and treatment. Nanomaterials have unique properties that other materials do not possess, such as a small size effect and quantum size effect. Introducing nanomaterials into biosensors improves the performance of biosensors for faster and more accurate detection of microorganisms and viruses. This review aims to introduce the different kinds of biosensors and the latest advances in the application of nanomaterials in biosensors. In particular, this review focuses on describing the physicochemical properties of zero-, one-, two-, and three-dimensional nanostructures as well as nanoenzymes. Finally, this review discusses the applications of nanobiosensors in the detection of microorganisms and viruses and the future directions of nanobiosensors.

Berberine ameliorates vascular dysfunction by downregulating TMAO-endoplasmic reticulum stress pathway via gut microbiota in hypertension.

The gut microbial metabolite trimethylamine N-oxide (TMAO) is regarded as a novel risk factor for hypertension. Berberine (BBR) exerts cardiovascular protective effects by regulating the gut microbiota-metabolite production pathway. However, whether and how BBR alleviates TMAO-induced vascular dysfunction in hypertension remains unclear. In the present study, we observed that plasma TMAO and related bacterial abundance were significantly elevated and negatively correlated with vascular function in 86 hypertensive patients compared with 46 normotensive controls. TMAO activated endoplasmic reticulum stress (ERS) signaling pathway to promote endothelial cell dysfunction and apoptosis in vitro. BBR (100, 200 mg ·â€¯kg-1 ·d-1) for 4 weeks ameliorates TMAO-induced vascular dysfunction and ERS activation in a choline-angiotensin II hypertensive mouse model. We found that plasma TMAO levels in 15 hypertensive patients treated with BBR (0.4 g, tid) were reduced by 8.8 % and 16.7 % at months 1 and 3, respectively, compared with pretreatment baseline. The oral BBR treatment also improved vascular function and lowered blood pressure. Faecal 16 S rDNA showed that BBR altered the gut bacterial composition and reduced the abundance of CutC/D bacteria in hypertensive mice and patients. In vitro bacterial cultures and enzyme reaction systems indicated that BBR inhibited the biosynthesis of TMAO precursor in the gut microbiota by binding to and inhibiting the activity of CutC/D enzyme. Our results indicate that BBR improve vascular dysfunction at least partially by decreasing TMAO via regulation of the gut microbiota in hypertension.

Involvement of METTL3-mediated m6A methylation in the early development of porcine cloned embryos.

METTL3-mediated N6-methyladenosine (m6A) modification is critical for gametogenesis and early embryonic development. However, the function of METTL3-mediated m6A modification in the early development of somatic nuclear transfer embryos (SCNT) remains unclear. Here, we found that METTL3 mRNA and protein levels exhibit dynamic changes during the early development of porcine SCNT embryos. The levels of METTL3 mRNA and protein in SCNT embryos at specific developmental stages differ from those in parthenogenetic activation (PA) counterparts. SiRNA injection effectively reduced the levels of METTL3 mRNA and protein in 4-cell embryos and blastocysts. METTL3 knockdown significantly reduced the cleavage and blastocyst rates of SCNT embryos. METTL3 knockdown significantly reduced the number of total cells and trophectoderm (TE) cells in the resulting blastocysts and perturbed cell lineage allocation. In addition, METTL3 knockdown reduced the levels of m6A modification in 4-cell embryos and blastocysts. Importantly, METTL3 knockdown decreased the expression levels of CDX2, GATA3, NANOG and YAP, and increased the expression levels of SOX2 and OCT4. Taken together, these results demonstrate that METTL3-mediated m6A modification regulates early development and lineage differentiation of porcine SCNT embryos.

Restricted health service utilization and subsequent positive self-care behavior during the early COVID-19 pandemic in China.

Background: The reallocation of health resources, epidemic prevention and control measures during the COVID-19 pandemic triggered widespread restricted health service utilization, some residents and patients tried positive self-care behavior to maintain their health, yet the efficacy of this intervention remains unclear. Object: Based on the reasoned action approach (RAA) theory, this study aimed to investigate the correlation between self-care behavior and restricted health service utilization among adults in China, trying to discover the vulnerable groups and external and intrinsic factors that affect self-care behavior among Chinese adults. Methods: Data on demographics, socioeconomic, health status, and self-care behavior were collected in "The Early China COVID-19 Survey," a cross-sectional anonymous online survey of the general population in China. Self-care behavior was measured by four indicators: weight control (WC), physical activity (PA), prevention behavior (PB), and online medical consultation (OMC). The multiple linear models and binary logistic regression were used to examine whether restricted health service utilization (RHSU) is associated with self-care behaviors; also, adjusted multivariate logistic regression was used to analyze subgroup heterogeneity. Results: In total, 8,428 adult participants completed the survey, the mean OMC score was 1.51 (SD 1.34), the mean PB score was 18.17 (SD 3.44), and the proportion of participants who engaged in WC and PA was 42.30 and 62.57%, respectively. According to the multiple regression model, the RHSU was significantly positively correlated with all four indicators of self-care (WC: OR = 1.34, p < 0.001, PA: OR = 1.34, p < 0.05, MC: OR = 1.30, p < 0.001, PB: coef = 0.16, p < 0.05). We also observed some significant differences in the intensity of this relationship by subgroup analysis, precisely, OMC (high vs. moderate vs. low infection-risk level: OR = 1.48; 1.41; 1.19, p < 0.1), PA (male vs. female: OR = 1.27;1.06; p < 0.05, high vs. Moderate and low infection-risk level: OR = 1.51; 1.17; 1.02, p < 0.05), PB (Chronic disease groups vs. no: coef = 0.46; 0.1, p < 0.05). Conclusion: Restricted health service utilization predicts more positive self-care behavior, and the intensity of partial correlation was significantly different in the subgroups of sex, actual infection risk level of the living area, and chronic diseases. These findings highlight the urgent demand for self-care behavior among Chinese adults during the pandemic and provide new insights for developing self-care and reducing the burden on the healthcare system in the long term.

Esculentoside H reduces the PANoptosis and protects the blood-brain barrier after cerebral ischemia/reperfusion through the TLE1/PI3K/AKT signaling pathway.

AIMS: Matrix metalloproteinases 9 (MMP9) plays a role in the destruction of blood-brain barrier (BBB) and cell death after cerebral ischemic/reperfusion (I/R). Esculentoside H (EH) is a saponin found in Phytolacca esculenta. It can block JNK1/2 and NF-κB signal mediated expression of MMP9. In this study, we determined whether EH can protect against cerebral I/R injury by inhibiting MMP9 and elucidated the underlying mechanism. MAIN METHODS: Male SD rats were used to construct middle cerebral artery occlusion (MCAO) models. We determined the effect of EH on MMP9 inhibition, BBB destruction, neuronal death, PANoptosis, infarct volume, and the protective factor TLE1. Adeno-associated virus (AAV) infection was used to establish TLE1 gene overexpression and knockdown rats, which were used to determine the function. LY294002 was used to determine the role of PI3K/AKT signaling in TLE1 function. KEY FINDINGS: After EH treatment, MMP9 expression, BBB destruction, neuronal death, and infarct volume decreased. We found that TLE1 expression decreased obviously after cerebral I/R. TLE1-overexpressing rats revealed distinct protective effects to cerebral I/R injury. After treatment with LY294002, the protective effect was inhibited. The curative effect of EH also decreased when TLE1 was knocked down. SIGNIFICANCE: EH alleviates PANoptosis and protects BBB after cerebral I/R via the TLE1/PI3K/AKT signaling pathway. Our findings reveal a novel strategy and new target for treating cerebral I/R injury.

[Research on Construction of Test Environment for Assessment of RF-Induced Heating Effects of Implants].

In magnetic resonance examination, the interaction between implants and the radio frequency (RF) fields induces heating in human tissue and may cause tissue damage. To assess the RF-induced heating of implants, three steps should be executed, including electromagnetic model construction, electromagnetic model validation, and virtual human body simulations. The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation. In this study, a hardware environment, comprised of a RF generation system, electromagnetic field measurement system, and a robotic arm positioning system, was established. Furthermore, an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment. The results indicate that the electric field generated in this test environment aligns well with the simulated electric field, making it suitable for assessing the RF-induced heating effects of implants.

HOT-GAN: Hilbert Optimal Transport for Generative Adversarial Network.

Generative adversarial network (GAN) has achieved remarkable success in generating high-quality synthetic data by learning the underlying distributions of target data. Recent efforts have been devoted to utilizing optimal transport (OT) to tackle the gradient vanishing and instability issues in GAN. They use the Wasserstein distance as a metric to measure the discrepancy between the generator distribution and the real data distribution. However, most optimal transport GANs define loss functions in Euclidean space, which limits their capability in handling high-order statistics that are of much interest in a variety of practical applications. In this article, we propose a computational framework to alleviate this issue from both theoretical and practical perspectives. Particularly, we generalize the optimal transport-based GAN from Euclidean space to the reproducing kernel Hilbert space (RKHS) and propose Hilbert Optimal Transport GAN (HOT-GAN). First, we design HOT-GAN with a Hilbert embedding that allows the discriminator to tackle more informative and high-order statistics in RKHS. Second, we prove that HOT-GAN has a closed-form kernel reformulation in RKHS that can achieve a tractable objective under the GAN framework. Third, HOT-GAN's objective enjoys the theoretical guarantee of differentiability with respect to generator parameters, which is beneficial to learn powerful generators via adversarial kernel learning. Extensive experiments are conducted, showing that our proposed HOT-GAN consistently outperforms the representative GAN works.

Identification of Immune-Related Gene Signature in Schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a type of psychiatric disorder characterized by multiple symptoms. Our aim is to decipher the relevant mechanisms of immune-related gene signatures in SCZ. METHODS: The SCZ dataset and its associated immunoregulatory genes were retrieved using Gene Expression Omnibus (GEO) and single-sample gene set enrichment analysis (ssGSEA). Co-expressed gene modules were determined through weighted gene correlation network analysis (WGCNA). To elucidate the functional characteristics of these clusters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used. Additionally, gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to identify enriched pathways for the immune subgroups. A protein-protein interaction (PPI) network analysis was performed to identify core genes relevant to SCZ. RESULTS: A significantly higher immune score was observed in SCZ compared to control samples. Seven distinct gene modules were identified, with genes highlighted in green selected for further analysis. Using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, degrees of immune cell adhesion and accumulation related to 22 different immune cell types were calculated. Significantly enriched bioprocesses concerning the immunoregulatory genes with differential expressions included interferon-beta, IgG binding, and response to interferon-gamma, according to GO and KEGG analyses. Eleven hub genes related to immune infiltration emerged as key players among the three top-ranked GO terms. CONCLUSIONS: This study underscores the involvement of immunoregulatory reactions in SCZ development. Eleven immune-related genes (IFITM1 (interferon induced transmembrane protein 1), GBP1 (guanylate binding protein 1), BST2 (bone marrow stromal cell antigen 2), IFITM3 (interferon induced transmembrane protein 3), GBP2 (guanylate binding protein 2), CD44 (CD44 molecule), FCER1G (Fc epsilon receptor Ig), HLA-DRA (major histocompatibility complex, class II, DR alpha), FCGR2A (Fc gamma receptor IIa), IFI16 (interferon gamma inducible protein 16), and FCGR3B (Fc gamma receptor IIIb)) were identified as hub genes, representing potential biomarkers and therapeutic targets associated with the immune response in SCZ patients.

[Response of Relationship Between Microplastic Abundance and Nitrogen Metabolism Function Microorganisms and Genes in Water].

The impact of microplastics (MPs) as a new type of pollutant on water pollution has become a research hotspot. To explore the response relationship between the abundance of MPs and nitrogen metabolism function in a freshwater environment, Lake Ulansuhai was used as the research object; the abundance of MPs in the water was detected using a Zeiss microscope, and the distribution characteristics of nitrogen metabolism functional bacteria and functional genes in the water were analyzed using metagenomics sequencing. The correlation analysis method was used to explore the relationship between the abundance of MPs and nitrogen metabolism functional microorganisms and nitrogen metabolism functional genes. The results showed that the presence of MPs in freshwater environments had a higher impact on Cyanobacteria and Firmicutes as the dominant phyla, and the presence of MPs promoted their enrichment and growth. Among the dominant bacterial genera, MPs promoted the growth of Mycobacterium and inhibited Candidatus_Planktopila more significantly, further indicating that in freshwater environments, MPs affected normal nitrogen metabolism by affecting microbial communities, and pathways such as carbon and nitrogen fixation and denitrification were important pathways for MPs to affect nitrogen metabolism. From the perspective of nitrogen metabolism functional genes, it was found that the abundance of MPs significantly affected some functional genes during nitrification (pmoA-amoA, pmoB-amoB, and pmoC-amoC), denitrification (nirK and napA), and dissimilatory nitrate reduction (nrfA) processes (P < 0.05). Moreover, the influence of MPs abundance on different functional genes in the same pathway of nitrogen metabolism varied, making the impact of MPs on aquatic environments very complex; thus, its harm to the water environment cannot be underestimated.

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

Association between estimated glucose disposal rate and atrial fibrillation recurrence in patients undergoing radiofrequency catheter ablation: a retrospective study.

OBJECTIVE: Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. METHODS: This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 - (0.22 * body mass index) - (3.26 * hypertension) - (0.61 * HbA1c). Cox proportional hazard regression models and exposure-effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p < 0.01). Participants with an eGDR ≥ 8 mg/kg/min had a lower risk of AF recurrence than those with an eGDR < 4 mg/kg/min, with a hazard ratio (HR) of 0.28 [95% confidence interval (CI) 0.18, 0.42]. Additionally, restricted cubic spline analyses demonstrated a linear association between the eGDR and AF recurrence (p nonlinear = 0.70). The area under the curve (AUC) for predicting AF recurrence using the eGDR was 0.75. CONCLUSIONS: The study revealed that a decrease in the eGDR is associated with a greater AF recurrence risk after RFCA. Hence, the eGDR could be used as a novel biomarker for assessing AF recurrence risk.