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Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.

High-entropy alloys (HEAs) demonstrate superior mechanical properties at room temperature, highlighting potential for engineering applications. With the increasing demand for advanced materials, especially in modern applications facing rigorous conditions, it becomes imperative to gain profound insights into the dynamic behavior of HEAs. In this study, the (FeCoNi)86Al7Ti7 HEA, renowned for exceptional printability and room-temperature mechanical properties, has been fabricated by selective laser melting (SLM), and its tensile and impact behaviors at ambient and cryogenic temperatures are systematically investigated. Experimental results reveal enhanced tensile properties as temperature decreases, achieving a high ultimate strength of 1313.6 MPa and impressive ductility of 24.8 % at 77 K. This improvement is attributed to the synergistic deformation mechanisms, including dislocation slip, stacking faults, Lomer and Lomer-Cottrell locks, which maintain a high strain-hardening rate and thus suppress strain localization. In contrast, impact properties deteriorate due to constrained dislocation mobility at high strain rates and low temperatures, with Charpy impact energy decreasing from 8.1 J at 293 K to 5.1 J at 77 K. Consequently, cracks readily initiate at cellular boundaries or defects, propagating in an intergranular manner and inducing localized deformation. This study provides valuable insights for the future applications of 3D-printed HEAs in extreme operational environments.

ABSTRACT: Since 2012, there has been a noticeable upward trend in the global incidence of inclusion body hepatitis (IBH) cases, leading to substantial economic losses in the poultry industry. In response to this trend, the current study aimed to investigate the phylogenetic information, genetic mutations, and pathogenicity of the highly pathogenic fowl adenovirus (FAdV) strain HN1472, which was isolated from liver samples obtained from a laying flock affected by IBH. This investigation was carried out using 1-day-old specific pathogen-free (SPF) chickens. Recombination and phylogenetic analyses confirmed that HN1472 is a recombinant strain derived from FAdV-8a and FAdV-8b, and exhibited significant genetic divergence in the hexon, fiber, and ORF19 genes. Notably, the phylogenetic analysis identified recombination events in these regions. Furthermore, animal experiments revealed that HN1472 is a highly pathogenic isolate, causing 80% mortality and manifesting clinical signs of IBH in SPF chickens. Furthermore, the recombinant FAdV serotype 8b (FAdV-8b) was found to be widely distributed in various tissues, with a higher concentration in the livers and gizzard tissue at 3 d postchallenge (dpc). Collectively, these findings contribute to our current understanding of the factors influencing the pathogenicity and genetic diversity of FAdV serotype 8b (FAdV-8b) in China.

Background: Patients with ulcerative colitis (UC) often exhibit susceptibilities to multiple autoimmune diseases such as Sjogren's syndrome, primary sclerosing cholangitis, systemic lupus erythematosus, and insulin-dependent diabetes mellitus. This propensity likely stems from common pathogenic mechanisms underlying immune-mediated conditions. This report highlights the occurrence of autoimmune thyroid disease during UC exacerbations. Notably, the patient displayed petrified auricles.Case Summary.A 57-year-old male complained of sustained abdominal pain, diarrhea, hematochezia, and mucus for a duration of 20 days. The diagnosis of UC was confirmed via colonoscopy, histopathological examination, and small bowel MRE. Clinical evaluations revealed bilateral ectopic ossification in his ears, which appeared to develop over an unspecified timeframe. Imaging and histological evaluations substantiated the ectopic ossification diagnosis while eliminating the possibility of adrenal insufficiency. The presented case offers a unique instance of bilateral auricular ossification, which is hypothesized to result from hyperthyroidism. Conclusion: Our case report underscores the necessity of enhancing awareness of the rare complications associated with UC. Medical practitioners should recognize the potential overlap of autoimmune thyroid disorders in UC patients. It is imperative to test for thyroid-related antibodies in such individuals, irrespective of overt thyroid dysfunction.

Atherosclerosis (AS) is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease, stroke, and peripheral vascular disease. Despite the current treatments, mortality and disability still remain high. Sonodynamic therapy (SDT), a non-invasive and localized methodology, has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques. Promising progress has been made through cell and animal assays, as well as clinical trials. For example, the effect of SDT on apoptosis and autophagy of cells in AS, especially macrophages, and the concept of non-lethal SDT has also been proposed. In this review, we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS; we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages, T lymphocytes, neovascularization, smooth muscle cells, lipid, extracellular matrix and efferocytosis within plaques; additionally, we discuss the safety of SDT. A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

ObjectiveTo explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).MethodsA child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.ResultsA ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.ConclusionThe diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

BackgroundThere are many problems of psychological burden in patients with tumor implanted in port of intravenous infusion. However, more attention is paid to its complications in the literature, and psychological problems are seldom concerned. The purpose of this study was to explore the psychological state and needs of tumor patients after implantation of an intravenous infusion port and provide valuable references for psychological interventions.MethodA semi-structured interview was conducted with 11 patients with intravenous infusion ports. Colaizzi’s 7-step analysis was used to analyze the interview data.ResultsAccording to the primary information, four themes and nine sub-themes were extracted: (1) lack of self-worth, (2) multiple emotional experiences (guilt, doubt, worry, and gain). (3) Poor self-management and self-maintenance awareness (over-reliance on medical staff, unchanged family roles, lack of related knowledge). (4) Expectations and suggestions for the future (inner expectations, suggestions for infusion ports).ConclusionThe patient’s psychological state should be carefully monitored during tube implantation, to relieve the patient’s tension and anxiety and improve nursing satisfaction and patient outcomes.

This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 μV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.

Abstract Mild‐heat photothermal antibacterial therapy avoids heat‐induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo‐conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co‐assemble with DSPE‐mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc+NIR‐II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR‐II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR‐II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR‐II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR‐II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics‐alternative anti‐infective measure.

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

Purpose: We aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases. Methods: HAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 μg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR；the apoptosis rate of the cells was detected by flow cytometry. Results: ① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 μg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 μg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 μg/mL groups was significantly lower than the normal control group at 24 h (P

ABSTRACT: To develop effective antibiotics alternatives is getting more and more important to poultry healthy production. The study investigated the effects of a microencapsulated essential oils and organic acids preparation (EOA) on growth performance, slaughter performance, nutrient digestibility and intestinal microenvironment of broilers. A total of 624 1-day-old male Arbor Acres broilers were randomly divided into 6 groups including the control group (T1) fed with basal diet, the antibiotic group (T2) supplemented with basal diet with 45 mg/kg bacitracin methylene disalicylate (BMD), and 4 inclusion levels of EOA-treated groups (T3, T4, T5, T6 groups) chickens given basal diet with 200, 400, 600, and 800 mg EOA/kg of diet, respectively. Results showed that compared with the control, the 200 mg/kg EOA group increased average daily gain (ADG) and average body weight (ABW) during the early stage (P < 0.05). EOA addition decreased crypt depth of the ileum (P < 0.05), but villus height to crypt depth ratio was increased by EOA addition at 200 and 400 mg/kg at d 21 (P < 0.05). Compared with the control, dietary addition EOA at 200, 400 and 600 mg/kg increased the lipase activity in the duodenum at d 21 (P < 0.05). Increased lactic acid bacteria population was found in cecal digesta of the 400 mg/kg EOA group at d 21 (P < 0.05), and higher concentration of butyric acid level was observed in cecal digesta at d 21 and d 42 in the 200 mg/kg EOA group compared with the control (P < 0.05). RT-PCR analysis found that dietary EOA addition decreased the gene expression of IL-1β, COX-2 and TGF-β4 in the ileum at d 21 (P < 0.05), while only the 200 mg/kg EOA increased the gene expression of IL-10, TGF-β4, Claudin-1, ZO-1, CATH-1, CATH-3, AvBD-1, AvBD-9 and AvBD-12 in the ileum at d 42 (P < 0.05) compared with the control. In summary, adding 200 mg/kg and 400 mg/kg of the EOA to the diet could improve the growth performance and intestinal microenvironment through improving intestinal morphology, increasing digestive enzymes activity and cecal lactic acid bacteria abundance and butyric acid content, improving intestinal barrier function as well as maintaining intestinal immune homeostasis. The improving effect induced by EOA addition in the early growth stage was better than that in the later growth stage. Overall, the EOA product might be an effective antibiotic alternative for broiler industry.

Multi-source sensor information fusion technology plays an important role in many application fields in the era of “Industry 4.0”. Generally, in practical engineering applications, the obtained information is inevitably uncertain due to the degradation of sensor performance, environmental interference, abnormal communication transmission process, etc. Compared with the strict requirements of probability density function for data quantity, the use of interval numbers to characterize the uncertainty of information has obvious advantages. Classical Dempster-Shafer(D-S) evidence theory can effectively deal with uncertain information, whereas its evidence structure is single-valued, making it difficult to fuse interval uncertainty information. Therefore, it is necessary to adopt an interval-valued evidence structure to carry out interval uncertainty information fusion. Current researches on interval-valued belief structure mainly focus on the modification of evidence combination rules but neglect the key problem of how to generate interval-valued evidence structure from original data obtained from sensors. Aiming at the problem of classification and discrimination based on multi-source interval-valued sensor information fusion, this paper adopts the theory of interval-valued evidence and focuses on the problem of generating a reasonable belief structure based on original interval-valued sensor information by using a multistage correction framework. Firstly, an interval-valued Lance and Williams Distance(ILWD) is proposed, and an initial belief structure is generated based on the proposed ILWD using the original sensor information. Secondly, by considering the interval length effect and based on Jaccard similarity coefficient, the initial interval-valued belief structure is corrected by a two-stage process. Then, in order to alleviate the impact of evidence conflict on the combination results, the weight of each evidence is assigned by an optimization method (the third stage of the belief structure modification). Further, the evidence is combined based on the method proposed by Wang et al. (2007). Finally, a practical case study is carried out to verify the rationality and effectiveness of the proposed method.

Developing eco-friendly, degradable, and flexible electronic devices using renewable cellulose, such as waste agricultural straw, is increasingly vital. This approach tackles the growing issue of nondegradable electronic waste. In this study, flexible transparent electrodes (FTEs) were created using cellulose from waste corn straw, embedding silver nanowires (AgNWs) networks within the surface layer. This method is suitable for reel-to-reel processing. These sustainable FTEs had high transparency and conductivity, with a film resistance of 45.4 Ω/sq and light transmittance of 86.2% at 550 nm. The "dissolution–regeneration" self-assembly process harnesses cellulose's hydrogen bond network to stabilize the AgNWs network, providing the FTEs with excellent electromechanical stability. Resistance changes were less than 3% during bending, folding, and 1,000-time cyclic bending tests. Furthermore, these electrodes showed remarkable environmental stability, with only a 2.5% resistance increase after 16 days at room temperature. This research demonstrates a new application for agricultural straw cellulose in flexible electronics, offering a sustainable alternative in electronic materials.

Foundation models have reshaped the landscape of remote sensing (RS) by enhancing various image interpretation tasks. Pretraining is an active research topic, encompassing supervised and self-supervised learning methods to initialize model weights effectively. However, transferring the pretrained models to downstream tasks may encounter task discrepancy due to their formulation of pretraining as image classification or object discrimination tasks. In this study, we explore the multitask pretraining (MTP) paradigm for RS foundation models to address this issue. Using a shared encoder and task-specific decoder architecture, we conduct multitask supervised pretraining on the segment anything model annotated remote sensing segmentation dataset, encompassing semantic segmentation, instance segmentation, and rotated object detection. MTP supports both convolutional neural networks and vision transformer foundation models with over 300 million parameters. The pretrained models are finetuned on various RS downstream tasks, such as scene classification, horizontal, and rotated object detection, semantic segmentation, and change detection. Extensive experiments across 14 datasets demonstrate the superiority of our models over existing ones of similar size and their competitive performance compared to larger state-of-the-art models, thus validating the effectiveness of MTP.

Abstract Background In the American population, the relationship between the triglyceride-glucose (TyG) index and TYG combined with indicators of obesity and cardiovascular disease (CVD) and its mortality has been less well studied. Methods This cross-sectional study included 11,937 adults from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Cox proportional hazards model, binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were used to analyze the relationship between TyG and its combined obesity-related indicators and CVD and its mortality. Mediation analysis explored the mediating role of glycated hemoglobin and insulin in the above relationships. Results In this study, except for no significant association between TyG and CVD mortality, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly and positively associated with CVD and CVD mortality. TyG-WHtR is the strongest predictor of CVD mortality (HR 1.66, 95% CI 1.21–2.29). The TyG index correlated better with the risk of coronary heart disease (OR 2.52, 95% CI 1.66–3.83). TyG-WC correlated best with total CVD (OR 2.37, 95% CI 1.77–3.17), congestive heart failure (OR 2.14, 95% CI 1.31–3.51), and angina pectoris (OR 2.38, 95% CI 1.43–3.97). TyG-WHtR correlated best with myocardial infarction (OR 2.24, 95% CI 1.45–3.44). RCS analyses showed that most of the above relationships were linear (P-overall 0.05). Otherwise, ROC curves showed that TyG-WHtR and TyG-WC had more robust diagnostic efficacy than TyG. In mediation analyses, glycated hemoglobin mediated in all the above relationships and insulin-mediated in partial relationships. Conclusions TyG-WC and TyG-WtHR enhance CVD mortality prediction, diagnostic efficacy of CVD and its mortality, and correlation with some CVD over and above the current hottest TyG. TyG-WC and TyG-WtHR are expected to become more effective metrics for identifying populations at early risk of cardiovascular disease and improve risk stratification.

Abstract Background Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. Methods The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3−), NK (NK1.1−CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. Results Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P

Abstract Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.

Abstract Background Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. Methods We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. Results Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. Conclusion Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.

Technological innovation represents the core driving force for the green development of resource-based enterprises. How to effectively promote enterprises’ technological innovation has received considerable attention in academia and practice. However, most of existing studies have been focused on the influence of industrial level or organizational level, the impact of leadership has received little attention. Therefore, this study explores the impact of environmental leadership, which focuses on environmental protection and sustainable development, on technological innovation. Using Stata 18 software, this study analyzes 170 resource-based enterprises listed on the Shenzhen and Shanghai A-share stock markets, for the time periods spanning from 2013 to 2022. The results indicate a positive impact of environmental leadership on technological innovation, with green investment mediating the relationship between environmental leadership and technological innovation. However, the moderating effect of government subsidies between environmental leadership and green investment is not significant. Our findings offer a better understanding of technological innovation in resource-based enterprises by considering the influence factors from both internal and external pespectives, especially the critical role of leader. Therefore, this study contributes to the literature on leadership theory and technological innovation theory.

Abstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of immunoinflammatory diseases. However, the role of NKG2D in neonatal HIBD is seldomly investigated. In this study, a neonatal mice model of HIBD was induced, and the role of the NKG2D in neuroinflammation and brain injury was explored by intracerebroventricular injection of lentivirus to knockdown NKG2D in neonatal mice with HIBD. The results showed that a significant increase in NKG2D protein level in the brain of neonatal mice with HIBD. The NKG2D knockdown in the brain significantly alleviated cerebral infarction, neurobehavioral deficits, and neuronal loss in neuronal HIBD. Moreover, the neuroprotective effect of NKG2D knockdown was associated with inhibition of the activation of microglia and astrocytes, expression of NKG2D ligands (NKG2DLs) and DAP10, and the nuclear translocation of NF-κB p65. Our findings reveal NKG2D knockdown may exert anti-inflammatory and neuroprotective effects in the neonatal mice with HIBD through downregulation of NKG2D/NKG2DLs/DAP10/NF-κB pathway. These results suggest that NKG2D may be a potential target for the treatment of neonatal HIBD.

Abstract Introduction The purpose of this study was to explore the effects of repeated low-level red-light (RLRL) therapy on the structure and vasculature of the choroid and retina in Chinese children with premyopia. Methods This study was a single-center randomized clinical trial. A total of 94 children with premyopia (− 0.50 D 0.05). Notably, RLRL therapy achieved a notable reduction in SE shift by 73.8%, a substantial decrease in AL change by 67.9%, and a significant reduction in myopia incidence by 45.1% within 1 year. Conclusion Our study demonstrated a significant increase in CT and flow in the RLRL-treated eyes throughout the 12-months of the study. Combined with its reduction in spherical equivalent progression and axial elongation, RLRL could be used as an effective therapy for preventing progression in premyopes. Trial Registration ChiCTR2200062028.

Ship detection in synthetic aperture radar (SAR) images using deep neural networks often relies on horizontal bounding box, which fail to capture ship orientation and aspect ratio accurately. To address this limitation, oriented ship detection methods based on oriented bounding box (OBB) are gaining attention. However, most available existing OBB methods suffer from boundary discontinuity problem, leading to convergence problems and unsatisfied orientation detection performance. In this article, we propose an innovative oriented SAR ship detection method using ellipse polar encoding (EPE). By representing the ship detection box as an ellipse and employing a set of vectors from the center to the boundary as encoded parameters, our method exhibits smooth variations, enhances convergence, and efficiently decodes into OBB. We further develop a lightweight and effective oriented SAR ship detection network based on this methodology. To account for SAR image characteristics, such as speckle and deformation causing deviations from true ellipses, we introduce an intersection over union weighted EPE loss. The experimental results on the rotated ship detection dataset in SAR images demonstrate the effectiveness of our proposed method in significantly improving detection performance compared with other oriented target detection methods.

The wear resistance of the part surface has become an important factor affecting its own service life. Laser cladding (LC), as a surface modification technology, can prepare a coating with good metallurgical bonding with the substrate, which can significantly improve the wear resistance of the material surface. High entropy alloys (HEAs) are an emerging coating material with excellent wear resistance. Therefore, this paper reviews the latest development status in wear resistance of laser cladding-high-entropy alloy coatings (LC-HEACs) in terms of the HEAs material system, LC process parameters, strengthening phase, amorphous phase strengthening, assisted cladding, and post-treatment. At the same time, this paper also expounds on the mechanism of LC-HEACs enhancing the surface wear resistance of materials, and the current research status of LC-HEACs in different engineering materials and application environments. Finally, the current research deficiencies, challenges, and future development trends of LC-HEACs in the field of wear resistance are also elaborated, and it is expected to provide some references for their future development and applications.

Using l-histidine and cerium nitrate hexahydrate as raw materials, a green and effective carbon dots (Ce,N-CDs) was prepared using hydrothermal synthesis and their structures were confirmed by professional equipment. The anti-bacterial and anti-corrosive behaviors of Ce,N-CDs were systemically evaluated using plate counting method and electrochemical method, respectively. By analysis, the Ce,N-CDs showed a high bacterial inhibition efficiency for Escherichia coli (E. coli), which was up to 94.27 %. Compared with N-doping carbon dots (N-CDs), the Ce,N-CDs exhibited an excellent anti-corrosive ability. At 200 mg/l, its corrosion inhibition efficiency (IE) for Cu was higher than 90 % at different environment temperatures (308, 318, 323 K), and the corrosion rate (WL) was sharply reduced. This was attributed to the presence of N–Cu bond and the formation of Ce-containing passive film. The Ce-containing passive film could block the erosion of aggressive ions. The N–Cu bond could facilitated the chemical adsorption on Cu surface, which was confirmed by quantum chemistry (QC) and molecular dynamics (MD).

Abstract Dianhong Black Tea, a fermented tea containing various bioactive ingredients, has been found to have a significant role in alleviating alcoholic liver injury (ALI). One of its main unique components, Dianhong Black Tea volatile substances (DBTVS), may have potential anti‐ALI effects. However, its effects and underlying molecular mechanisms are still unknown. In this study, we aimed to investigate the potential of DBTVS as an anti‐ALI agent using alcohol‐fed rats. We assessed the effect of DBTVS on ALI by analyzing serum transaminase and lipid levels, as well as conducting hematoxylin–eosin and oil red O staining. Additionally, GC‐MS was used to detect the components of DBTVS, while transcriptome, proteomics analysis, Western blot, and molecular docking were employed to uncover the underlying mechanisms. Our results demonstrated that DBTVS significantly reduced serum ALT and AST levels and improved lipid metabolism disorders. Moreover, we identified 14 components in DBTVS, with five of them exhibiting strong binding affinity with key proteins. These findings suggested that DBTVS could be a promising agent for the prevention and treatment of ALI. Its potential therapeutic effects may be attributed to its ability to regulate lipid metabolism through the PPAR signaling pathway.

Background and Aims: There are limited contemporary population-based data on Helicobacter pylori epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with H pylori testing or treatment using Veterans Health Administration data. Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for H pylori infection (3 algorithms) and treatment status (1 algorithm). During the development phase, we iteratively modified each algorithm based on a manual review of random sets of electronic health records (reference standard). The a priori validation goal was to achieve a one-sided 95% confidence lower bound (LB) for positive predictive value (PPV) and/or negative predictive value (NPV) >90%. We applied the Bonferroni correction when both PPV and NPV were relevant. Results: For H pylori infection, we achieved 99.0% PPV (LB = 94.6%) and 100% NPV (LB = 96.4%) for discriminating H pylori positive vs negative status using structured (ie, laboratory tests) and 95% PPV (LB = 90.3%) and 97.9% NPV (LB = 93.9%) using unstructured (ie, histopathology reports) data. Diagnostic codes achieved 98% PPV (LB = 93.0%) for H pylori diagnosis. The treatment algorithm was composed of multiple antimicrobial combinations and overall achieved ≥98% PPV (LB = 93.0%) for H pylori treatment, except for amoxicillin/levofloxacin (PPV

Abstract Background Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections (RTIs) have become the primary cause of death for T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa RTI in T2DM individuals and elucidate its underlying mechanism. Methods High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a RTI model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa RTI were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. Results We found that P. aeruginosa RTI was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa RTI in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa RTI by acarbose in nondiabetic mice. Conclusions This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.

Abstract Background Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries. Methods Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes. Results Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility. Conclusions The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes.

Abstract Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.

Abstract Investigating the influencing factors of new‐onset hypertension in the elderly with obstructive sleep apnea (OSA). 450 Chinese older patients with OSA who were non‐hypertensive at baseline were enrolled. All patients had undergone polysomnography monitoring in the multicenter study. The primary endpoint was incident hypertension. Kaplan–Meier survival analysis was performed, and multivariate Cox proportional hazards models were generated to determine the factors influencing new‐onset hypertension. A total of 176 (39.1%) patients developed hypertension. The hypertension group had older age, higher hemoglobin (Hb) level and apnea‐hypopnea index (AHI) values than the non‐hypertension group (all p

Angiotensin-converting enzyme 2 (ACE2) and several proteins have been identified as entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether long noncoding RNAs are involved in SARS-CoV-2 entry remains unknown. In this study, we investigated the role of small nucleolar RNA host gene 15 (SNHG15) in SARS-CoV-2 entry using a SARS-CoV-2 spike pseudotyped lentivirus with a luciferase reporter. Overexpression of SNHG15 promoted but SNHG15 knockdown limited SARS-CoV-2 entry in a dose- and time-dependent manner. SNHG15 interacted with Rab-like protein 2A (RABL2A). Overexpression and knockdown of RABL2A produced similar effects on SARS-CoV-2 entry as those of SNHG15. Furthermore, RABL2A knockdown abolished the SNHG15-mediated increase in SARS-CoV-2 entry. In conclusion, SNHG15 is a critical regulatory factor that aids SARS-CoV-2 entry through RABL2A.

AIM: To investigate the effect of morroniside (Mor) on lipopolysaccharide (LPS)-treated iris pigment epithelial cells (IPE). METHODS: IPE cells were induced by LPS and treated with Mor. Cell proliferation was detected by cell counting kit (CCK) -8, apoptosis was detected by flow cytometry, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) kits, and the protein expression of TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 was analyzed by Western blotting. In addition, overexpression of TLR4 and Mor treatment of LPS-stimulated IPE cells were also tested for the above indices. RESULTS: Mor effectively promoted the proliferation and inhibited the apoptosis of LPS-treated IPE cells. In addition, Mor significantly reduced the levels of TNF-α, IL-6, and IL-8 and significantly inhibited the expression of TLR4, p-JAK2, and p-STAT3 in LPS-treated IPE cells. The effect of Mor on LPS-treated IPE cells was markedly attenuated after overexpression of TLR4. CONCLUSION: These findings suggest that Mor may ameliorate LPS-induced inflammatory damage and apoptosis in IPE through inhibition of TLR4/JAK2/STAT3 pathway.

The surface water in the Qinghai–Tibet Plateau (QTP) region has undergone dramatic changes in recent decades. To capture dynamic surface water information, many satellite imagery-based methods have been proposed. However, these methods are still limited in terms of automation and accuracy and thus prevent surface water dynamic studies in large-scale QTP regions. In this study, we developed a new fully automatic method for accurate surface water mapping by using Sentinel-1 synthetic aperture radar (SAR) imagery and convolutional networks (ConvNets). Specifically, we built a new multiscale ConvNet structure to improve the model capability in surface water body extraction. Moreover, a gating mechanism is introduced to promote the efficient use of multiscale information. According to the accuracy assessment, the proposed gated multiscale ConvNet (GMNet) achieved the highest overall accuracy of 98.07%. We applied our GMNet for monthly surface water mapping on the QTP; accordingly, we found that the QTP region experienced significant surface water fluctuations over one year. The surface water also showed distinct spatial heterogeneity on the QTP; that is, the surface water fraction of the Inner Tibetan Basin was significantly higher than that of the Mekong Basin in both the wet and dry seasons.

AbstractHelicobacter pylori (H. pylori) is recognized as a pathogen associated with several gastrointestinal diseases. The current treatments exhibit numerous drawbacks, including antibiotic resistance. H. pylori can adhere to and colonize the gastric mucosa through H. pylori adhesin A (HpaA), and antibodies against HpaA may be an effective therapeutic approach. The variable domain of immunoglobulin new antigen receptor (VNAR) is a novel type of single-domain antibody with a small size, good stability, and easy manufacturability. This study isolated VNARs against HpaA from an immune shark VNAR phage display library. The VNARs can bind both recombinant and native HpaA proteins. The VNARs, 2A2 and 3D6, showed high binding affinities to HpaA with different epitopes. Furthermore, homodimeric bivalent VNARs, biNb-2A2 and biNb-3D6, were constructed to enhance the binding affinity. The biNb-2A2 and biNb-3D6 had excellent stability at gastrointestinal pH conditions. Finally, a sandwich ELISA assay was developed to quantify the HpaA protein using BiNb-2A2 as the capture antibody and BiNb-3D6 as the detection antibody. This study provides a potential foundation for novel alternative approaches to treatment or diagnostics applications of H. pylori infection.

Abstract Background The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. Methods This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). Results A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131–3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. Conclusions The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

Compared to the middle and shallow strata, the engineering geological characteristics of Weirong deep shale gas are more complex, with the four characteristics of high ground stress, high horizontal stress difference, high plasticity, and high formation pressure. The complex engineering geological characteristics bring three major challenges: difficulty in forming complex fracture networks, difficulty in supporting and maintaining artificial fractures, and frequent occurrence of abnormal situations such as casing deformation. The specific performance result is the low single well EUR after gas well fracturing. Through unremitting exploration and practice, the fracturing technology has been continuously improved in the process of discovering and solving problems, and a series of measures of "fine optimization, real-time warning, operating pace control, and W-shaped well network" for preventing casing deformation and increasing post fracturing output has been formed based on the concept of balanced fracturing. The technology has been promoted and applied in 39 wells, and the fracturing effect has been continuously improved, with an average EUR increase of 500×104 m3 per well, and a decrease of casing deformation rate from 42.4% in 2022 to 16.67% at present. Due to the impact of the production of adjacent old wells on the production of newly fractured production wells, the output of new wells after fracturing is lower than the previous stage. With the existing well spacing of 400 m (Phase Ⅰ)/300 m (Phase Ⅱ), there is room for reduction and optimization in fracturing scale. Subsequent new wells should be differentiated and optimized based on remaining reserves, and research on fracturing technology shall be carried out continuously, achieving the beneficial development of Weirong deep shale gas.

Abstract Introduction This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). Methods This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73–34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or

Abstract This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

Abstract Objective Prior research has revealed a heightened prevalence of neoplasms in individuals diagnosed with rheumatoid arthritis (RA). The primary objective of this study is to delve into the causal association between RA and two distinct types of neoplasms: benign neoplasm of bone and articular cartilage (BNBAC) and malignant neoplasm of bone and articular cartilage (MNBAC). Methods We employed summary data from genome-wide association analyses (GWAS) to investigate the causal relationship between RA and two neoplasms, BNBAC and MNBAC, using a two-sample bidirectional Mendelian randomization (MR) study design. The IEU OpenGWAS database provided the GWAS summary data for RA, while the Finnish consortium supplied the GWAS summary data for BNBAC and MNBAC. Our analysis involved the utilization of eight distinct MR methods, namely random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed effects IVW. Subsequently, we conducted assessments to evaluate heterogeneity, horizontal pleiotropy, outliers, the impact of a single-nucleotide polymorphism (SNP), and adherence to the assumption of normal distribution in the MR analysis. Results The results from the MR analysis revealed that there was no significant genetic association between RA and BNBAC (P = 0.427, odds ratio [OR] 95% confidence interval [CI] = 0.971 [0.904–1.044]). However, a positive genetic association was observed between RA and MNBAC (P = 0.001, OR 95% CI = 1.413 [1.144–1.745]). Conducting a reverse MR analysis, we found no evidence to support a genetic causality between BNBAC (P = 0.088, OR 95% CI = 1.041 [0.994–1.091]) or MNBAC (P = 0.168, OR 95% CI = 1.013 [0.995–1.031]) and RA. Our MR analysis demonstrated the absence of heterogeneity, horizontal pleiotropy, and outliers and confirmed that the effect was not driven by a single SNP. Additionally, the data exhibited a normal distribution. Conclusion The findings of this study demonstrate that RA constitutes a significant risk factor for MNBAC. In the context of clinical application, it is advisable to conduct MNBAC screening in RA patients and remain vigilant regarding its potential manifestation. Importantly, the outcomes of this investigation introduce a fresh vantage point into the understanding of the tumorigenesis associated with RA.

Abstract Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial–mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3′-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC. Graphical Abstract

Tea is one of the most popular non-alcoholic beverages in the world, and free amino acids, especially theanine, make a major contribution to the umami taste of tea. However, the genetic basis of the variation in amino acid content in tea plants remains largely unknown. Here, we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing. Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids. A total of 69 quantitative trait loci (–log10(P-value)>5) were identified. Functional annotation revealed that branched-chain amino acid aminotransferase, glutamine synthetase, nitrate transporter, and glutamate decarboxylase might be important for amino acid metabolism. Two significant loci, glutamine synthetase (Glu1, P=3.71×10−4; Arg1, P=4.61×10−5) and branched-chain amino acid aminotransferase (Val1, P=4.67×10−5; I_Leu1, P=3.56×10−6), were identified, respectively. Based on the genotyping result, two alleles of CsGS (CsGS-L and CsGS-H) and CsBCAT (CsBCAT-L and CsBCAT-H) were selected to perform function verification. Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants, and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine, isoleucine and leucine. Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine. Furthermore, CsGS-L and CsGS-H differentially regulated the accumulation of glutamine, and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids. In summary, the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.

Anisotropic microstructure and mechanical properties are vital considerations in the practical applications of 3D-printed metallic materials; however, limited attention has been given to the anisotropy in 3D-printed high entropy alloys (HEAs). This study systematically explores the structural and mechanical anisotropy of (FeCoNi)86Al7Ti7 HEA with low porosity, fabricated via selective laser melting (SLM). The SLM process, characterized by directional and repeated thermal dissipation, creates an anisotropic structure consisting of epitaxial columnar grains aligned parallel to the building direction, subsequently influencing mechanical anisotropy. Tensile testing unveils slight anisotropy in strength but significant differences in ductility for the SLMed HEA. The 0° sample demonstrates the optimal combination of strength and plasticity, boasting a tensile elongation of 31.5 %, approximately 2.6 times higher than that of the 45° and 90° samples. The post-mortem microscopic analysis indicates that this ductility anisotropy primarily originates from the crack propagation behavior. In the 0° sample, crack propagation occurs through both intergranular and transgranular modes, with the robust interactions between the two modes providing an obstruction to crack propagation. On the contrary, crack widening occurs essentially along the continuous melting pool boundaries (MPBs) in 45° and 90° samples, leading to the straight crack propagation path along the MPBs and therefore reduced ductility.

In electromagnetic launching systems, arc erosion of rail material, such as Al2O3 dispersion-strengthened copper (ODS-Cu), remains a critical unresolved issue. Here, we report a cold-sprayed CuCrZr–W coating on ODS-Cu exhibiting enhanced arc erosion resistance. The coating was fabricated using a bimodal powder mixture comprising coarse CuCrZr and fine W particles, resulting in a dense structure with an embedded networks of fine W particles along intersplat boundaries. Compared to the ODS-Cu substrate, the CuCrZr–W coating displays superior arc erosion resistance, as evidenced by the reduced arc erosion area and depth, shorter arc duration, lower wielding force, and limited molten Al adhesion during arcing tests. The enhanced performance is attributed to a high density of W/CuCrZr interfaces that effectively disperse arcs, the W particle network that alters the flow path of molten Cu, lowering splashing and evaporation. This work provides valuable insights into developing high-performance, arc erosion-resistant coatings for applications where safeguarding against arc erosion is paramount.

In this paper, the process of solid-state metalized reduction and magnetic separation was investigated for preparation of nickel–iron concentrate from a low-grade laterite nickel ore. The effects of reduction temperature, reduction time, amount of dosages, and magnetic field strength on grades and recoveries of nickel and iron were studied. The results showed that nickel–iron concentrate with a nickel grade of 7.32%, nickel recovery of 81.84%, iron grade of 78.74%, and iron recovery of 69.78% were obtained under the conditions of a reduction temperature of 1200 °C, reduction time of 120 min, calcium fluoride addition of 12%, ferric oxide addition of 10%, coal addition of 12%, and magnetic field strength of 170 kA/m.

Molecular dynamics (MD) simulations were first employed to achieve the optimal sintering temperature of carboxyl-functionalized graphene (GNS-COOH)-modified polyether ether ketone (PEEK)/polytetrafluoroethylene (PTFE) composites. A model of GNS-COOH/PEEK/PTFE composites was constructed to simulate the effects of different sintering temperatures on the mechanical and tribological properties, as well as their underlying atomic mechanisms. Samples of PTFE composites were prepared and characterized through experimental methods. Results revealed that the sintering temperature significantly affects the intermolecular forces, mechanical properties, and tribological characteristics of the composites. The agglomeration of the PEEK/PTFE composite matrix was effectively mitigated by introducing GNS-COOH. When the sintering temperature was controlled at 360 °C, the compressive strength of GNS-COOH/PEEK/PTFE composites was improved compared to GNS/PEEK/PTFE composites, albeit with a slight reduction in wear resistance. This study provides a theoretical reference for the preparation process and performance evaluation of new materials.

There is a growing trend in incorporating biomass-based engineered nanomaterials into food products to enhance their quality and functionality. The zeta potential, droplet size, microstructure, and content of free fatty acid (FFA) release were determined to investigate the influence of a plant-derived particle stabilizer, i.e., lignin-containing cellulose nanofibrils (LCNFs). Remarkable differences were observed during digestion stages, which were found to be correlated with the concentrations of LCNFs. The gradual FFA release in the small intestine stage from LCNF-coated lipid droplets was monitored over time, with a final lowest release of FFAs amounting to 26.3% in the emulsion containing 20.0% (v/v) of the dispersed phase stabilized by 3 mg/mL of LCNFs. This release can be attributed to the physical barrier at lipid droplet surfaces and the network effect created by the free LCNFs in the continuous phase. This work provides a foundation for the potential application of nature-derived LCNF materials in reducing fat absorbance.

Based on an in-depth analysis of the factors influencing the compressive strength of ultra-high-performance concrete (UHPC), this study examined the impact of both single factorsand combined factors on UHPC performance using experimental data. The correlation analysis indicates that cement content, water content, steel fiber, and fly ash significantly affect the strength of UHPC, whereas silica fume, superplasticizers, and slag powder have a relatively smaller influence. This analysis provides a scientific basis for model development. Furthermore, the support vector regression (SVR) model was optimized using the arithmetic optimization algorithm (AOA). The superior performance and computational efficiency of the AOA–SVR model in predicting UHPC compressive strength were validated. Compared to SVR, support vector machine (SVM), and other single models, the AOA–SVR model achieves the highest R2 value and the lowest error rates. The results demonstrate that the optimized AOA–SVR model possesses excellent generalization ability and can more accurately predict the compressive strength of UHPC.