Impedance Sliding-Mode Control Based on Stiffness Scheduling for Rehabilitation Robot Systems.

Rehabilitation robots can reproduce the rehabilitation movements of therapists by designed rehabilitation robot control methods to achieve the goal of training the patients' motion abilities. This paper proposes an impedance sliding-mode control method based on stiffness-scheduled law for the rehabilitation robot, which can be applied to rehabilitation training with both active and passive modes. A free-model-based sliding-mode control strategy is developed to avoid model dependence and reduce the system uncertainty caused by limb shaking. Additionally, the stiffness scheduling rule automatically regulates the impedance parameter of the rehabilitation robot based on the force exerted by the patient on the robot such that the rehabilitation training caters to the patient's health condition. The proposed method is compared with the fixed stiffness and variable stiffness impedance methods, and the superiority of the proposed method is proved. Rehabilitation training experiments on an actual rehabilitation robot are provided to demonstrate the feasibility and stability of the proposed method.

KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS.

BACKGROUND: Inflammation is one of the significant consequences of ox-LDL-induced endothelial cell (EC) dysfunction. The senescence-associated secretory phenotype (SASP) is a critical source of inflammation factors. However, the molecular mechanism by which the SASP is regulated in ECs under ox-LDL conditions remains unknown. RESULTS: The level of SASP was increased in ox-LDL-treated ECs, which could be augmented by KLF4 knockdown whereas restored by KLF4 knock-in. Furthermore, we found that KLF4 directly promoted PDGFRA transcription and confirmed the central role of the NAPMT/mitochondrial ROS pathway in KLF4/PDGFRA-mediated inhibition of SASP. Animal experiments showed a higher SASP HFD-fed mice, compared with normal feed (ND)-fed mice, and the endothelium of EC-specific KLF4-/- mice exhibited a higher proportion of SA-ß-gal-positive cells and lower PDGFRA/NAMPT expression. CONCLUSIONS: Our results revealed that KLF4 inhibits the SASP of endothelial cells under ox-LDL conditions through the PDGFRA/NAMPT/mitochondrial ROS. METHODS: Ox-LDL-treated ECs and HFD-fed mice were used as endothelial senescence models in vitro and in vivo. SA-ß-gal stain, detection of SAHF and the expression of inflammatory factors determined SASP and senescence of ECs. The direct interaction of KLF4 and PDGFRA promotor was analyzed by EMSA and fluorescent dual luciferase reporting analysis.

The relationship between glycemic risk and longitudinal changes in total physiological atherosclerotic burden in patients with coronary artery disease.

Background: The effects of glycemic status on coronary physiology have not been well evaluated. This study aimed to investigate changes in coronary physiology by using angiographic quantitative flow ratio (QFR), and their relationships with diabetes mellitus (DM) and glycemic control status. Methods: This retrospective cohort study included 530 patients who underwent serial coronary angiography (CAG) measurements between January 2016 and December 2021 at Tongji Hospital of Tongji University. Based on baseline and follow-up angiograms, 3-vessel QFR (3V-QFR) measurements were performed. Functional progression of coronary artery disease (CAD) was defined as a change in 3V-QFR (Δ3V-QFR = 3V-QFRfollow-up - 3V-QFRbaseline) ≤-0.05. Univariable and multivariable logistic regression analyses were applied to identify the independent predictors of coronary functional progression. Subgroup analysis according to diabetic status was performed. Results: During a median interval of 12.1 (10.6, 14.3) months between the two QFR measurements, functional progression was observed in 169 (31.9%) patients. Follow-up glycosylated hemoglobin (HbA1c) was predictive of coronary functional progression with an area under the curve (AUC) of 0.599 [95% confidence interval (CI): 0.546-0.651; P<0.001] in the entire population. Additionally, the Δ3V-QFR values were significantly lower in diabetic patients with HbA1c ≥7.0% compared to those with well-controlled HbA1c or non-diabetic patients [-0.03 (-0.09, 0) vs. -0.02 (-0.05, 0.01) vs. -0.02 (-0.05, 0.02); P=0.002]. In a fully adjusted multivariable logistics analysis, higher follow-up HbA1c levels were independently associated with progression in 3V-QFR [odds ratio (OR), 1.263; 95% CI: 1.078-1.479; P=0.004]. Furthermore, this association was particularly strong in diabetic patients (OR, 1.353; 95% CI: 1.082-1.693; P=0.008) compared to patients without DM. Conclusions: Among patients with established CAD, on-treatment HbA1c levels were independently associated with progression in physiological atherosclerotic burden, especially in patients with DM.

Toll-like receptors in health and disease.

Toll-like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation-related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR-related diseases.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

The application of autofluorescence system contributes to the preservation of parathyroid function during thyroid surgery.

PURPOSE: The purpose of this study was to investigate the impact of autofluorescence technology on postoperative parathyroid function and short-term outcomes in patients undergoing thyroid surgery. METHODS: A total of 546 patients were included in the study, with 287 in the conventional treatment group and 259 in the autofluorescence group. Both groups underwent central lymph node dissection, which is known to affect parathyroid function. Short-term outcomes, including rates of postoperative hypocalcemia and parathyroid dysfunction, serum calcium and PTH levels on the first postoperative day, as well as the need for calcium supplementation, were analyzed. A multivariable analysis was also conducted to assess the impact of autofluorescence on postoperative parathyroid dysfunction, considering factors such as age, BMI, and preoperative calcium levels. RESULTS: The autofluorescence group demonstrated significantly lower rates of postoperative hypocalcemia and parathyroid dysfunction compared to the conventional treatment group. The autofluorescence group also had better serum calcium and PTH levels on the first postoperative day, and a reduced need for calcium supplementation. Surprisingly, the use of autofluorescence technology did not prolong surgical time; instead, it led to a shorter hospitalization duration. The multivariable analysis showed that autofluorescence significantly reduced the risk of postoperative parathyroid dysfunction, while factors such as age, BMI, and preoperative calcium levels did not show a significant correlation. CONCLUSION: This study provides evidence that autofluorescence technology can improve the preservation of parathyroid function during thyroid surgery, leading to better short-term outcomes and reduced postoperative complications. The findings highlight the potential of autofluorescence as a valuable tool in the management of parathyroid hypofunction. Further research and validation are needed to establish the routine use of autofluorescence technology in the thyroid.

Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of ß-catenin.

BACKGROUND: Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive. METHODS: The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of ß-catenin and active ß-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on ß-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear ß-catenin signaling. RESULTS: CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of ß-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between ß-catenin and ß-TrCP1, consequently impeding the ubiquitination process of ß-catenin and activating the nuclear ß-catenin signaling. CONCLUSIONS: CDH4 induces PTC angiogenesis and metastasis via the inhibition of ß-TrCP1-dependent ubiquitination of ß-Catenin.

Manganese-facilitated dynamic active-site generation on Ni2P with self-termination of surface reconstruction for urea oxidation at high current density.

Electrochemical urea oxidation reaction (UOR) suffers from sluggish reaction kinetics due to its complex 6-electron transfer processes combined with conversion of complicated intermediates, severely retarding the overall energy conversion efficiency. Herein, manganese-doped nickel phosphide nanosheets (Mn-Ni2P) are constructed and employed for driving UOR. Comprehensive analysis deciphers that Mn doping could efficiently accelerate the surface reconstruction of Mn-Ni2P electrode, generating highly reactive NiOOH-MnOOH heterostructure with local nucleophilic and electrophilic regions. Such unique structure could accelerate the targeted adsorption and activation of C and N atoms, promoting fracture of CN bond in urea. In addition, moderate Mn doping could efficiently enhance the adsorption capacities of urea molecules and some key intermediates, and minish the energy barrier for *CO2 desorption, accelerating refreshing of the catalyst. Consequently, the Mn-Ni2P electrode exhibits excellent UOR catalytic activity, achieving an industrial-level current density of 1000 mA cm-2 at 1.46 V (vs. RHE).

A "Mesh Scaffold" that regulates the mechanical properties and restricts the phase transition-induced volume change of the PNIPAM-based hydrogel for wearable sensors.

Poly(N-isopropylacrylamide) (PNIPAM) is capable of improving the reversibility and responsiveness of flexible electronics. However, its phase transition-induced volume variation and poor adhesiveness remain limitations for expending its applications. Herein, a pressure-sensitive adhesive (PSA), which is a type of mesh scaffold, is constructed inside the network of PNIPAM, providing the hydrogel with a constant volume in response to different temperatures, in situ tunable mechanical properties, and superior adhesiveness. The reversible density of the mesh scaffold adjusts the aggregation state of the hydrogel chains, whereupon it is capable of changing its mechanical modulus from 6.7 kPa to 45.3 kPa. This mechanical mechanism contributes to hydrogel-based flexible devices for multiple applications, especially in pressure-related sensors. The mesh scaffold restricts the phase-transition-induced volume variation, which allows the hydrogel sensor to stably monitor the external pressure at various temperatures. The high adhesion enables the effective interfacial interaction with the skin, avoiding the loss of sensing signals during the detection of human body movements. When it is assembled into an electronic device, it can transmit information and recognize sign language via Morse code. Thus, herein, we report a hydrogel sensor that is promising for pressure detection in temperature-unstable environments, especially for managing the health of patients who require emergency medical care through sign language recognition.

Degradation of Nitrobenzene by Mackinawite through a Sequential Two-Step Reduction and Oxidation Process.

Mackinawite (FeS) has gained increasing interest due to its potential application in contaminant removal by either reduction or oxidation processes. This study further demonstrated the efficiency of FeS in degrading nitrobenzene (ArNO2) via a sequential two-step reduction and oxidation process under neutral conditions. In the reduction stage, FeS rapidly reduced ArNO2 to aniline (ArNH2), with nitrosobenzene (ArNO) and phenylhydroxylamine (ArNHOH) serving as the intermediates. X-ray photoelectron spectroscopy (XPS) analysis indicated that both Fe(II) and S(II) in FeS contributed electrons to the reduction of ArNO2. In the subsequent oxidation stage with oxygen, by addition of 0.5 mM tripolyphosphate (TPP), ArNH2 generated in the reduction process could be effectively oxidized to aminophenols by hydroxyl radicals (•OH), which would undergo eventual mineralization via ring-cleavage reactions. TPP exerted a favorable role in enhancing •OH production for ArNH2 degradation by promoting the formation of the dissolved Fe(II)-TPP complex, thus enhancing the homogeneous Fenton reaction. Additionally, TPP adsorption inhibited the surface oxidation reactivity of FeS due to the change of Fe(II) coordination. Finally, the effective degradation of ArNO2 by FeS in actual groundwater was demonstrated by using this sequential reduction and oxidation approach. These research findings provide a theoretical basis for a new FeS-based remediation approach, offering an alternative way for comprehensive removal of ArNO2.

Flexible Strain-Sensitive Sensors Assembled from Mussel-inspired Hydrogel with Tunable Mechanical Properties and Wide Temperature Tolerance in Multiple Application Scenarios.

Conductive hydrogels, exhibiting wide applications in electronic skins and soft wearable sensors, often require maturely regulating of the hydrogel mechanical properties to meet specific demands and work for a long-term or under extreme environment. However, in situ regulation of the mechanical properties of hydrogels is still a challenge, and regular conductive hydrogels will inevitably freeze at subzero temperature and easily dehydrate, which leads to a short service life. Herein, a novel adhesive hydrogel (PAA-Dopa-Zr4+) capable of strain sensing is proposed with antifreezing, nondrying, strong surface adhesion, and tunable mechanical properties. 3,4-Dihydroxyphenyl-l-alanine (l-Dopa)-grafted poly(acrylic acid) (PAA) and Zr4+ ion are introduced into the hydrogel, which broadly alters the mechanical properties via tuning the in situ aggregation state of polymer chains by ions based on the complexation effect. The catechol groups of l-Dopa and viscous glucose endow the hydrogel with high adhesiveness for skin and device interface (including humid and dry environments) and exhibit an outstanding temperature tolerance under extreme wide temperature spectrum (-35 to 65 °C) or long-lasting moisture retention (60 days). Furthermore, this PAA-Dopa-Zr4+ can be assembled as a flexible strain-sensitive sensor to detect human motions based on specific mechanical properties requirements. This work, enabling superior adhesive and temperature tolerance performance and broad mechanical tenability, presents a new paradigm for numerous applications to wearable sensing and personalized healthcare monitoring.

Using machine learning to detect sarcopenia from electronic health records.

Introduction: Sarcopenia (low muscle mass and strength) causes dysmobility and loss of independence. Sarcopenia is often not directly coded or described in electronic health records (EHR). The objective was to improve sarcopenia detection using structured data from EHR. Methods: Adults undergoing musculoskeletal testing (December 2017-March 2020) were classified as meeting sarcopenia thresholds for 0 (controls), ≥1 (Sarcopenia-1), or ≥2 (Sarcopenia-2) tests. Electronic health record diagnoses, medications, and laboratory testing were extracted from the Indiana Network for Patient Care. Five machine learning models were applied to EHR data for predicting sarcopenia. Results: Of 1304 participants, 1055 were controls, 249 met Sarcopenia-1 and 76 met Sarcopenia-2. Sarcopenic participants were older, with higher fat mass, Charlson Comorbidity Index, and more chronic diseases. All models performed better for Sarcopenia-2 than Sarcopenia-1. The top performing models for Sarcopenia-1 were Logistic Regression [area under the curve (AUC) 71.59 (95% confidence interval [CI], 71.51-71.66)] and Multi-Layer Perceptron [AUC 71.48 (95%CI, 71.00-71.97)]. The top performing models for Sarcopenia-2 were Logistic Regression [AUC 91.44 (95%CI, 91.28-91.60)] and Support Vector Machine [AUC 90.81 (95%CI, 88.41-93.20)]. For the best Logistic Regression Model, important sarcopenia predictors included diabetes mellitus, digestive system complaints, signs and symptoms involving the nervous, musculoskeletal and respiratory systems, metabolic disorders, and kidney or urinary tract disorders. Opioids, corticosteroids, and antihyperlipidemic drugs were also more common among sarcopenic participants. Conclusions: Applying machine learning models, sarcopenia can be predicted from structured data in EHR, which may be developed through future studies to facilitate large-scale early detection and intervention in clinical populations.

Causal inference during closed-loop navigation: parsing of self- and object-motion.

A key computation in building adaptive internal models of the external world is to ascribe sensory signals to their likely cause(s), a process of causal inference (CI). CI is well studied within the framework of two-alternative forced-choice tasks, but less well understood within the cadre of naturalistic action-perception loops. Here, we examine the process of disambiguating retinal motion caused by self- and/or object-motion during closed-loop navigation. First, we derive a normative account specifying how observers ought to intercept hidden and moving targets given their belief about (i) whether retinal motion was caused by the target moving, and (ii) if so, with what velocity. Next, in line with the modelling results, we show that humans report targets as stationary and steer towards their initial rather than final position more often when they are themselves moving, suggesting a putative misattribution of object-motion to the self. Further, we predict that observers should misattribute retinal motion more often: (i) during passive rather than active self-motion (given the lack of an efference copy informing self-motion estimates in the former), and (ii) when targets are presented eccentrically rather than centrally (given that lateral self-motion flow vectors are larger at eccentric locations during forward self-motion). Results support both of these predictions. Lastly, analysis of eye movements show that, while initial saccades toward targets were largely accurate regardless of the self-motion condition, subsequent gaze pursuit was modulated by target velocity during object-only motion, but not during concurrent object- and self-motion. These results demonstrate CI within action-perception loops, and suggest a protracted temporal unfolding of the computations characterizing CI. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Dramatically enhanced phenol degradation upon FeS oxygenation by low-molecular-weight organic acids.

Oxidizing potential of FeS for organic contaminants degradation due to hydroxyl radicals (•OH) production has been recently documented, but the oxidizing efficiency was limited. Here, we revealed that low-molecular-weight organic acids (LMWOAs) can immensely enhance phenol degradation during FeS oxygenation due to increased utilization efficiency of FeS electron for •OH production. Upon oxygenation of 0.5 g/L FeS, phenol degradation boosted from 7.1% without LMWOAs to 91.5%, 84.6% and 95.0% with the addition of 1 mM oxalate, citrate and EDTA, respectively. Electron utilization efficiency of Fe(II) for •OH production dramatically rose from 0.3% with FeS alone to respective 2.0%, 2.5% and 2.7% in the LMWOAs systems. An increase in oxalate concentrations benefited •OH formation and phenol degradation. Coexisting oxalate led to an additional •OH production pathway from Fe(II)-oxalate oxidation, which expanded the O2 reduction to H2O2 from a two- to one-electron transfer process. Meanwhile, electron transfer from FeS to dissolved Fe(III)-oxalate promoted the redox cycling of Fe(III)/Fe(II), thus supplying the Fe(II) oxidation for •OH production. Moreover, the presence of oxalate decreased the crystallinity and particles size of lepidocrocite generated from FeS oxidation. Consequently, this study shed lights on the LMWOAs-enhanced contaminant degradation in either natural or engineered FeS oxidation systems.

Activation of NLRP3 Inflammasome via Drp1 Overexpression in Kupffer Cells Aggravates Ischemia-reperfusion Injury in Hepatic Steatosis.

Background and Aims: Donors with fatty livers are considered to address the shortage of livers for transplantation, but those livers are particularly sensitive to ischemia-reperfusion injury (IRI), and an increased incidence of graft failure is observed. Kupffer cells account for 20-35% of liver nonparenchymal cells, and have been shown to participate in the process of IRI and inflammatory reactions of hepatic steatosis. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is an intracellular sensor activated by Kupffer cells to promote generation and participates in IRI. Dynamics-associated protein 1 (Drp1) is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial dynamics. The mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been clarified. Methods: A mouse model of hepatic steatosis was established by feeding the mice with a high-fat diet. In vitro experiments were performed using AML12 normal mouse liver cells and RAW264.7 mononuclear macrophage cells cultured in medium with palmitate and oleic acid. Western blotting and immunohistochemical (IHC) staining were used to detect the expression of NLRPP3 and Drp1 in IRI in the control and high-fat diet groups. The expression of F4/80+ cells during IRI in hepatic steatosis was verified by IHC staining, and the role of NLRPP3 and Drp1 in Kupffer-cell mediated IRI was investigated by targeting Drp-1 inhibition. Results: Drp1 and NLRP3 expression was increased during IRI in hepatic steatosis, and the expression of Drp1 and NLRP3 were decreased after the elimination of Kupffer cells. That indicated Kupffer cells were involved in the process of IRI in hepatic steatosis through the action of Drp1 and NLRP3. After Drp1 inhibition, liver function was restored and NLRP3 expression level was reduced. Conclusions: Kupffer cells aggravated IRI in hepatic steatosis via NLRP3 and Drp1. Drp1 inhibitors might be useful as specific therapeutics to alleviate IRI in hepatic steatosis and may have promise in case of liver donor shortage.

Screening of Potential Circulating Diagnostic Biomarkers and Molecular Mechanisms of Systemic Lupus Erythematosus-Related Myocardial Infarction by Integrative Analysis.

Background: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data. Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE. Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils. Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.

NUDT5-Determines the fate of head and neck squamous cell carcinoma cells under endoplasmic reticulum stress by catalyzing nuclear ATP production to promote DNA repair.

OBJECTIVES: NUDT5 is the only discovered enzyme that catalyses ATP production in cell nuclei. In this study, we investigate the character of NUDT5 in head and neck squamous cell carcinoma (HNSCC) cells under endoplasmic reticulum (ER) stress. METHODS: The formation of ER stress was confirmed in HNSCC cells using Real-time PCR and Western blot techniques. The expression of NUDT5 was modified by transfecting HNSCC cells with siRNA and plasmids, respectively. The effects of NUDT5 manipulation were assessed using various methods including cell counting kit-8 assay, western blotting, RNA sequencing, Immunofluorescence Microscopy analysis, cell cycle analysis and nucleic ATP measurement, and a xenograft mouse model. RESULTS: In this study, we found that the expression of NUDT5 proteins was upregulated under ER stress conditions in HNSCC cells. Knocking down NUDT5 under ER stress could hinder nuclear ATP generation and thus induce more DNA damage and apoptosis of HNSCC cells. Only the wild-type NUDT5 or ATP catalysis active mutant T45A-NUDT5, rather than the ATP catalysis null mutant T45D-NUDT5, could directly rescue nuclear ATP depletion caused by NUDT5 inhibition and protect HNSCC cells from DNA damage and cell apoptosis. Finally, in vivo studies showed that knocking down NUDT5 in ER-stressed conditions could significantly inhibit tumour growth. CONCLUSION: Our study demonstrated for the first time that NUDT5 guaranteed the integrity of DNA under ER stress-triggered DNA damage by catalysing nuclear ATP production. Our findings offer new insights into how the energy supply in cell nuclei fuels cancer cell survival in stressful microenvironment.

Direct Synthesis of Vertical Self-Assembly Oriented Hexagonal Boron Nitride on Gallium Nitride and Ultrahigh Photoresponse Ultraviolet Photodetectors.

The applications of three-dimensional materials combined with two-dimensional materials are attractive for constructing high-performance electronic and photoelectronic devices because of their remarkable electronic and optical properties. However, traditional preparation methods usually involve mechanical transfer, which has a complicated process and cannot avoid contamination. In this work, chemical vapor deposition was proposed to vertically synthesize self-assembly oriented hexagonal boron nitride on gallium nitride directly. The material composition, crystalline quality and orientation were investigated using multiple characterization methods. Thermal conductivity was found to be enhanced twofold in the h-BN incorporated sample by using the optothermal Raman technique. A vertical-ordered (VO)h-BN/GaN heterojunction photodetector was produced based on the synthesis. The photodetector exhibited a high ultraviolet photoresponsivity of up to 1970.7 mA/W, and detectivity up to 2.6 × 1013 Jones, and was stable in harsh high temperature conditions. Our work provides a new synthesis method to prepare h-BN on GaN-based materials directly, and a novel vertically oriented structure of VO-h-BN/GaN heterojunction, which has great application potential in optoelectronic devices.