DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer.

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .

Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.

Background: Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. Methods: We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study. Results: We found that ubiquitin-specific protease 14 (USP14) was significantly increased in lenvatinib-resistant HCC cells and tumors. Silencing USP14 significantly attenuated lenvatinib resistance in vitro and in vivo. Mechanistically, USP14 directly interacts with and stabilizes calcium- and integrin-binding protein 1 (CIB1) by reversing K48-linked proteolytic ubiquitination at K24, thus facilitating the P21-activated kinase 1 (PAK1)-ERK1/2 signaling axis. Moreover, in vivo adeno-associated virus 9 mediated transduction of CIB1 promoted lenvatinib resistance in PDXs, whereas CIB1 knockdown resensitized the response of PDXs to lenvatinib. Conclusions: These findings provide new insights into the role of CIB1/PAK1-ERK1/2 signaling in lenvatinib resistance in HCC. Targeting CIB1 and its pathways may be a novel pharmaceutical intervention for the treatment of lenvatinib-resistant HCC.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Expression profiling and function analysis identified new genes regulating cumulus expansion and apoptosis.

Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Effectiveness of preoperative and perioperative pulmonary rehabilitation nursing program for the management of patients undergoing thoracic surgery: A systematic review and meta-analysis.

Background & Objective: Several studies have investigated the effectiveness of preoperative or perioperative pulmonary rehabilitation in thoracic surgery patients, but the results are inconsistent and inconclusive. This study attempts to summarize the existing data on the effect of the preoperative and perioperative pulmonary rehabilitation nursing program for the management of patients undergoing thoracic surgery. Methods: Systematic search was done in PubMed Central, SCOPUS, EMBASE, MEDLINE, Google Scholar, and ScienceDirect for papers published until December 2022 and reporting data of postoperative complications and pulmonary health status in patients undergoing thoracic surgery and receiving preoperative or perioperative pulmonary rehabilitation nursing intervention or standard care. Meta-analysis was done by random-effects model and pooled standardised mean differences (SMD) or odds ratios (OR) along with 95% confidence intervals (CIs) were reported. Results: Eighteen studies were included and analysed. Pooled SMD was 0.44 (95%CI: -0.21 to 1.08) for forced expiratory volume (FEV-1), -0.34 (95%CI: -0.94 to 0.26) for peak expiratory flow (PEF), 0.61 (95%CI: -0.60 to 1.81) for forced vital capacity (FVC), 0.42 (95%CI: -0.13 to 0.98) for diffusing capacity of carbon monoxide (DLCO). Pooled SMD for length of hospital stay was -0.64 (95%CI: -1.09 to -0.19). Pooled OR was 0.87 [95%CI: 0.32 to 2.37] for all-cause mortality, 0.35 [95%CI: 0.25 to 0.50] for postoperative pulmonary complications, 0.98 [95%CI: 0.45 to 2.12] for respiratory failure, 0.52 [95%CI: 0.38 to 0.78] for pneumonia and 0.50 [95%CI: 0.33 to 0.76] for atelectasis. Conclusion: Perioperative pulmonary rehabilitation nursing program is effective in reducing the postoperative lung complications and shortening the length of hospital stay in patients undergoing thoracic surgery.

Electrochemical CO2 Reduction to Multicarbon Products on Non-Copper Based Catalysts.

Electrochemical CO2 reduction reaction (eCO2RR) to value-added multicarbon (C2+) products offers a promising approach for achieving carbon neutrality and storing intermittent renewable energy. Copper (Cu)-based electrocatalysts generally play the predominant role in this process. Yet recently, more and more non-Cu materials have demonstrated the capability to convert CO2 into C2+, which provides impressive production efficiency even exceeding those on Cu, and a wider variety of C2+ compounds not achievable with Cu counterparts. This motivates us to organize the present review to make a timely and tutorial summary of recent progresses on developing non-Cu based catalysts for CO2-to-C2+. We begin by elucidating the reaction pathways for C2+ formation, with an emphasis on the unique C-C coupling mechanisms in non-Cu electrocatalysts. Subsequently, we summarize the typical C2+-involved non-Cu catalysts, including ds-, d- and p-block metals, as well as metal-free materials, presenting the state-of-the-art design strategies to enhance C2+ efficiency. The system upgrading to promote C2+ productivity on non-Cu electrodes covering microbial electrosynthesis, electrolyte engineering, regulation of operational conditions, and synergistic co-electrolysis, is highlighted as well. Our review concludes with an exploration of the challenges and future opportunities in this rapidly evolving field.

Compact hard x-ray flash radiography device based on wire-shorted low-impedance rod pinch diode.

A rod pinch diode (RPD) is a feasible load configuration to generate a high-brightness, small-size hard x-ray radiation source. In this paper, the radiography performance of a wire-shorted low-impedance RPD on a compactly designed table-top driver (WRPD-1) is demonstrated for the first time. The driver consists of four high-power discharge branches connected in parallel, with each branch consisting of two metal-film capacitors and one multigap field-distortion switch in series. The four branches are triggered synchronously to generate a fast-rising current pulse: the inductance of the load section at the short circuit is ∼10 nH, and the short-circuit current amplitude is ∼325 kA at ±90 kV charging voltage, with a 10%-90% rise time of 110 ns. With a low-impedance RPD shorted by an 18-µm-diameter aluminum wire, a quasi-spherical x-ray focal spot with diameter <0.6 mm (width of the half-maximum grayscale) and a pulse duration of ∼25 ns (half-width of the radiation pulse) is obtained at ±70 kV charging voltage, and the imaging resolution excels 10 lp/mm under 1.56× magnification. According to the transmission-absorption x-ray spectrum estimation, the average emitted photon energy is ∼30 keV with a distinct peak in the 10-15 keV range that corresponds to the L-lines of tungsten, and the total energy of photons >10 keV reaches ∼1.16 J. The present results show that the device can serve well for the flash radiography diagnosis and potentially as an efficient light source for dynamic x-ray diffraction.

A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris.

Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid ß-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.

Random survival forest for predicting the combined effects of multiple physiological risk factors on all-cause mortality.

Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999-2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated (ECMO-RESCUE): study protocol for a prospective, multicentre, non-randomised cohort study.

INTRODUCTION: Severe septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the impaired cardiac function in patients with septic shock remains controversial. Moreover, no prospective studies have been taken to address whether venoarterial ECMO treatment could improve the outcome of patients with sepsis-induced cardiogenic shock. The objective of this study is to assess whether venoarterial ECMO treatment can improve the 30-day survival rate of patients with sepsis-induced refractory cardiogenic shock. METHODS AND ANALYSIS: ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated is a prospective, multicentre, non-randomised, cohort study on the application of ECMO in SCM. At least 64 patients with SCM and RSS will be enrolled in an estimated ratio of 1:1.5. Participants taking venoarterial ECMO during the period of study are referred to as cohort 1, and patients receiving only conventional therapy without ECMO belong to cohort 2. The primary outcome is survival in a 30-day follow-up period. Other end points include survival to intensive care unit (ICU) discharge, hospital survival, 6-month survival, quality of life for long-term survival (EQ-5D score), successful rate of ECMO weaning, long-term survivors' cardiac function, the number of days alive without continuous renal replacement therapy, mechanical ventilation and vasopressor, ICU and hospital length of stay, the rate of complications potentially related to ECMO treatment. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2020-hs-51). Participants will be screened and enrolled from ICU patients with septic shock by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION NUMBER: NCT05184296.

Microporous Materials in Polymer Electrolytes: The Merit of Order.

Solid-state batteries (SSBs) have garnered significant attention in the critical field of sustainable energy storage due to their potential benefits in safety, energy density, and cycle life. The large-scale, cost-effective production of SSBs necessitates the development of high-performance solid-state electrolytes. However, the manufacturing of SSBs relies heavily on the advancement of suitable solid-state electrolytes. Composite polymer electrolytes (CPEs), which combine the advantages of ordered microporous materials (OMMs) and polymer electrolytes, meet the requirements for high ionic conductivity/transference number, stability with respect to electrodes, compatibility with established manufacturing processes, and cost-effectiveness, making them particularly well-suited for mass production of SSBs. This review delineates how structural ordering dictates the fundamental physicochemical properties of OMMs, including ion transport, thermal transfer, and mechanical stability. The applications of prominent OMMs are critically examined, such as metal-organic frameworks, covalent organic frameworks, and zeolites, in CPEs, highlighting how structural ordering facilitates the fulfillment of property requirements. Finally, an outlook on the field is provided, exploring how the properties of CPEs can be enhanced through the dimensional design of OMMs, and the importance of uncovering the underlying "feature-function" mechanisms of various CPE types is underscored.

Identification of TonB-dependent siderophore receptor inhibitors against Flavobacterium columnare using a structure-based high-throughput virtual screening method.

TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.

Minimally invasive power sources for implantable electronics.

As implantable medical electronics (IMEs) developed for healthcare monitoring and biomedical therapy are extensively explored and deployed clinically, the demand for non-invasive implantable biomedical electronics is rapidly surging. Current rigid and bulky implantable microelectronic power sources are prone to immune rejection and incision, or cannot provide enough energy for long-term use, which greatly limits the development of miniaturized implantable medical devices. Herein, a comprehensive review of the historical development of IMEs and the applicable miniaturized power sources along with their advantages and limitations is given. Despite recent advances in microfabrication techniques, biocompatible materials have facilitated the development of IMEs system toward non-invasive, ultra-flexible, bioresorbable, wireless and multifunctional, progress in the development of minimally invasive power sources in implantable systems has remained limited. Here three promising minimally invasive power sources summarized, including energy storage devices (biodegradable primary batteries, rechargeable batteries and supercapacitors), human body energy harvesters (nanogenerators and biofuel cells) and wireless power transfer (far-field radiofrequency radiation, near-field wireless power transfer, ultrasonic and photovoltaic power transfer). The energy storage and energy harvesting mechanism, configurational design, material selection, output power and in vivo applications are also discussed. It is expected to give a comprehensive understanding of the minimally invasive power sources driven IMEs system for painless health monitoring and biomedical therapy with long-term stable functions.

Regio- and Diaseteroselective Synthesis of Polysubstituted Piperidines Enabled by Boronyl Radical-Catalyzed (4+2) Cycloaddition.

Piperidines are widely present in small molecule drugs and natural products. Despite many methods have been developed for their synthesis, new approaches to polysubstituted piperidines are highly desirable. This work presents a radical (4+2) cycloaddition reaction for synthesis of piperidines featuring dense substituents at 3,4,5-positions that are not readily accessible by known methods. Using commercially available diboron(4) compounds and 4-phenylpyridine as the catalyst precursors, the boronyl radical-catalyzed cycloaddition between 3-aroyl azetidines and various alkenes, including previously unreactive 1,2-di-, tri-, and tetrasubstituted alkenes, has delivered the polysubstituted piperidines in generally high yield and diastereoselectivity. The reaction also features high modularity, atom economy, broad substrate scope, metal-free conditions, simple catalysts and operation. The utilization of the products has been demonstrated by selective transformations. A plausible mechanism, with the ring-opening of azetidine as the rate-limiting step, has been proposed based on the experimental and computational results.

Inferring single-cell spatial gene expression with tissue morphology via explainable deep learning.

The spatial arrangement of cells is vital in developmental processes and organogenesis in multicellular life forms. Deep learning models trained with spatial omics data uncover complex patterns and relationships among cells, genes, and proteins in a high-dimensional space, providing new insights into biological processes and diseases. State-of-the-art in silico spatial multi-cell gene expression methods using histological images of tissue stained with hematoxylin and eosin (H&E) to characterize cellular heterogeneity. These computational techniques offer the advantage of analyzing vast amounts of spatial data in a scalable and automated manner, thereby accelerating scientific discovery and enabling more precise medical diagnostics and treatments. In this work, we developed a vision transformer (ViT) framework to map histological signatures to spatial single-cell transcriptomic signatures, named SPiRiT ( S patial Omics P rediction and R eproducibility integrated T ransformer). Our framework was enhanced by integrating cross validation with model interpretation during hyper-parameter tuning. SPiRiT predicts single-cell spatial gene expression using the matched histopathological image tiles of human breast cancer and whole mouse pup, evaluated by Xenium (10x Genomics) datasets. Furthermore, ViT model interpretation reveals the high-resolution, high attention area (HAR) that the ViT model uses to predict the gene expression, including marker genes for invasive cancer cells ( FASN ), stromal cells ( POSTN ), and lymphocytes ( IL7R ). In an apple-to-apple comparison with the ST-Net Convolutional Neural Network algorithm, SPiRiT improved predictive accuracy by 40% using human breast cancer Visium (10x Genomics) dataset. Cancer biomarker gene prediction and expression level are highly consistent with the tumor region annotation. In summary, our work highlights the feasibility to infer spatial single-cell gene expression using tissue morphology in multiple-species, i.e., human and mouse, and multi-organs, i.e., mouse whole body morphology. Importantly, incorporating model interpretation and vision transformer is expected to serve as a general-purpose framework for spatial transcriptomics.

Highly Sensitive Detection of Hydrogen Peroxide in Cancer Tissue Based on 3D Reduced Graphene Oxide-MXene-Multi-Walled Carbon Nanotubes Electrode.

Hydrogen peroxide (H2O2) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more H2O2 during abnormal tumor growth. There has been a considerable amount of interest in utilizing H2O2 as a biomarker for the diagnosis of cancer tissue. In this study, an electrochemical sensor for H2O2 was constructed based on 3D reduced graphene oxide (rGO), MXene (Ti3C2), and multi-walled carbon nanotubes (MWCNTs) composite. Three-dimensional (3D) rGO-Ti3C2-MWCNTs sensor showed good linearity for H2O2 in the ranges of 1-60 µM and 60 µM-9.77 mM at a working potential of -0.25 V, with sensitivities of 235.2 µA mM-1 cm-2 and 103.8 µA mM-1 cm-2, respectively, and a detection limit of 0.3 µM (S/N = 3). The sensor exhibited long-term stability, good repeatability, and outstanding immunity to interference. In addition, the modified electrode was employed to detect real-time H2O2 release from cancer cells and cancer tissue ex vivo.

Modulation of electronic structure of Ni3S2 via Fe and Mo co-doping to enhance the bifunctional electrocatalytic activities for HER and OER.

Heazlewoodite nickel sulfide (Ni3S2) is advocated as a promising nonnoble catalyst for electrochemical water splitting because of its unique structure configuration and high conductivity. However, the low active sites and strong sulfur-hydrogen bonds (S-Hads) formed on Ni3S2 surface greatly inhibit the desorption of Hads and reduce the hydrogen and oxygen evolution reaction (HER and OER) activity. Doping is a valid strategy to stimulate the intrinsic catalytic activity of pristine Ni3S2 via modifying the active site. Herein, the Ni foam supported Fe and Mo co-doped Ni3S2 electrocatalysts (Fe-MoS2/Ni3S2@NF) have been constructed using Keplerate polyoxomolybdate {Mo72F30} as precursor through a facile hydrothermal process. Experimental results certificate that Fe and Mo co-doping can effectively tune the local electronic structure, facilitate the interfacial electron transfer, and improve the intrinsic activity. Consequently, the Fe-MoS2/Ni3S2@NF display more excellent HER and OER activity than MoS2/Ni3S2@NF and bare Ni3S2@NF by delivering the 10 and 50 mA cm-2 current densities at ultra-low overpotentials of 74/175 and 80/160 mV for HER and OER. Moreover, when coupled in an alkaline electrolyzer, Fe-MoS2/Ni3S2@NF approached the current of 10 mA cm-2 under a cell voltage of 1.60 V and exhibit excellent stability. The strategy to realize tunable catalytic behaviors via foreign metal doping provides a new avenue to optimize the water splitting catalysts.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet ß cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. METHODS: db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein-protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. RESULTS: In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers. CONCLUSIONS: PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.

Limited Revision with a Newly Designed Hinge Device for the Treatment of Mega-Prosthesis Hinge Failure: Two Case Reports.

BACKGROUND: Surgical treatment for hinge failure in mega-prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision. CASE PRESENTATION: We here present two patients who underwent mega-prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega-prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful. CONCLUSIONS: Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old-fashioned mega-prosthesis hinges.