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Abstract Active and stable electrocatalysts are essential for hydrogen production from alkaline water electrolysis. However, precisely controlling the interaction between electrocatalysts and reaction intermediates (H2O*, H*, and *OH) remains challenging. Here, we demonstrate an yttrium-doped NiMo-MoO2 heterogenous electrocatalyst that efficiently promotes water dissociation and accelerates the intermediate adsorption/desorption dynamics in alkaline electrolytes. Introducing yttrium into the NiMo/MoO2 heterostructure induces lattice expansion and optimizes the d-band center of NiMo alloy component, enhancing water dissociation and H* desorption. Yttrium doping also increases the concentration of oxygen vacancies in MoO2−x, which in turn accelerates the charge kinetics and the swift evacuation of *OH intermediates from the active sites. Consequently, the Y-NiMo/MoO2−x heterostructure exhibits notable performance by requiring only 189 and 220 mV overpotentials to achieve current density of 2.0 A cm−2 in alkaline water and seawater, respectively. This work provides a strategy to modulate heterostructure catalysts for scalable, economically viable hydrogen production from low-quality waters.

Abstract Background Aberrant interplay between epigenetic reprogramming and metabolic rewiring events contributes to bladder cancer progression and metastasis. How the deacetylase Sirtuin-6 (SIRT6) regulates glycolysis and lactate secretion in bladder cancer remains poorly defined. We thus aimed to study the biological functions of SIRT6 in bladder cancer. Methods Bioinformatic analysis was used to study the prognostic significance of SIRT6/UHRF1 in BLCA. Both in vitro and in vivo assays were used to determine the roles of SIRT6/UHRF1 in BLCA. Deacetylation and ubiquitin assays were performed to uncover the regulations of SIRT6-UHRF1. Measurement of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) was used to assess glycolytic abilities. Results Here, we show that protein deacetylase SIRT6 was down-regulated in BLCA, and predicts poor overall survival. SIRT6 deficiency notably enhances BLCA cell proliferation, self-renewal, and migration capacities in vitro and in vivo. Mechanistically, SIRT6 interacts with, deacetylates, and promotes UHRF1 degradation mediated by β-TrCP1. Thus, SIRT6 deficiency leads to stabilized UHRF1 and depends on UHRF1 to accelerate BLCA malignant progression. Furthermore, UHRF1 significantly increased aerobic glycolysis via activating MCT4/HK2 expressions. Down-regulated SIRT6 thus depended on UHRF1 to promote glycolysis and lactate secretion in BLCA. Targeting UHRF1 or MCT4 notably impaired the extracellular lactate accumulations in BLCA. Significantly, a specific small-molecule inhibitor (NSC232003) targeting UHRF1 substantially inhibited SIRT6-deficient BLCA progression. Conclusion Together, our study uncovered an epigenetic mechanism of the SIRT6/UHRF1 axis in driving BLCA glycolysis and lactate secretion, creating a novel vulnerability for BLCA treatment.

Background Pseudomonas aeruginosa (P. aeruginosa) is widely distributed in air, soil, and water, human respiratory tract, intestinal tract, and skin. It can induce bloodstream infection, urinary tract infection, gastrointestinal tract infection, respiratory tract infection, etc. Conventional bacterial isolation, culture, and identification are time-consuming, and many false negative results, which cannot meet the needs of precise clinical diagnosis，and proper treatment. This study aims to develop a rapid isothermal amplification assay of Pseudomonas aeruginosa.Methods Specific primers were designed according to the National Center for Biotechnology Information (NCBI) database based on the highly conserved sequence of Pseudomonas aeruginosa virulence factor gene lecA, and a recombinase polymerase amplification (RPA) detection method was established. The sensitivity and specificity were calculated, as well as the collection and processing of clinical samples.Results The thermostatic amplification technique for Pseudomonas aeruginosa established in this paper allows nucleic acid detection within 10 minutes without cross-amplification with other bacterial strains. 27 P. aeruginosa infections were accurately detected in 300 clinical samples.Conclusion The rapid detection system based on thermostatic amplification had shown high sensitivity and specificity in this study, indicated that this method can effectively assist clinical bacterial detection.

Objective: Discuss the value of Artificial Intelligence (AI) in post-processing head and carotid artery CTA images and diagnosing head and carotid artery stenosis. Methods: The imaging data of 42 patients who all underwent head and neck CTA and digital subtraction angiography (DSA) of head and carotid arteries from November 2022 to October 2023 at our hospital were retrospectively collected. Image post-processing and diagnosis were divided into AI and manual groups to compare the differences in image post-processing time and subjective scores of image quality and identification of head and carotid artery plaque properties (calcified plaque, non-calcified plaque and mixed plaque) between the two groups. To compare the differences in sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two groups in diagnosing head and neck artery stenosis, using DSA results as the gold standard, and to perform the Kappa test for consistency between the two groups’ diagnostic results and DSA results. The diagnostic efficacy of the AI and manual groups on the head and carotid artery stenosis was analyzed by subject operator characteristic curve (ROC) and compared by Z-test. Results: The post-processing and diagnostic time in the AI group was (366.48±18.54) s, which was approximately 71.65% shorter than that in the manual group (1291.63±52.27) s. The difference was statistically significant. The difference between the subjective scores of image quality obtained by the two methods was not statistically significant. A total of 145 head and neck artery plaques were identified in the manual group and 145 in the AI group, of which 141 plaques of different nature were accurately identified in the AI group, with an overall accuracy rate of 97.24% (141/145). There was no statistically significant difference between the AI group and the manual group for identifying calcified plaque, non-calcified plaque and mixed plaque in the head and carotid arteries, and the agreement between the two groups for identifying the nature of plaque was good (Kappa=0.845). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the AI group in diagnosing head and neck artery stenosis were 87.09% (27/31), 81.82% (9/11), 93.10% (27/29), 69.23% (9/13) and 85.71% (36/42), respectively, which were in good agreement with DSA in diagnosing head and neck artery stenosis (Kappa= 0.792). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the manual group in diagnosing head and neck artery stenosis were 90.32% (28/31), 81.82% (9/11), 93.33% (28/30), 75.00% (9/12) and 88.10% (37/42), respectively, which were in good agreement with DSA in diagnosing head and neck artery stenosis (Kappa=0.801), and the difference in diagnostic efficacy was not statistically significant in either group. The results of the ROC curve analysis showed that the area under the curve (AUC) for the diagnosis of head and neck artery stenosis was 0.845 and 0.861 in the AI and manual groups, respectively, with no significant difference. Conclusion: AI technology has high clinical value in time spent on post-processing head and neck CTA images, assessing head and neck artery stenosis and identifying the nature of carotid plaque, and can be used as a useful aid for physicians in analyzing and diagnosing head and neck CTA.

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Abstract Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

Abstract Asthma is a complex chronic respiratory inflammatory disease affected by both genetic and environmental factors. Therefore, our study explored the influence of TRIM11 on asthma and its underlying mechanisms. Our research involved patients diagnosed with asthma and healthy volunteers recruited from our hospital. We observed a reduction in serum TRIM11 expression in asthma patients, which positively correlated with the levels of anti-IgE or IgE. Additionally, both TRIM11 mRNA and protein expression in lung tissue were diminished. The introduction of the TRIM11 gene resulted in a reduction in inflammation in an in vitro asthma model and prevented the development of asthma in a mouse model. Moreover, the TRIM11 gene exhibited a suppressive effect on Ferroptosis and mitigated ROS-induced mitochondrial damage in the asthma model. TRIM11 was found to stimulate UBE2N-TAX1BP1 signaling in the asthma model, with UBE2N being identified as the specific target for TRIM11’s effects on Ferroptosis. Furthermore, TRIM11 protein interacted with UBE2N protein and facilitated the dissociation of UBE2N-UBE2N in the asthma model. In conclusion, TRIM11 plays a vital role in preventing Ferroptosis in the asthma model through UBE2N-TAX1BP1 signaling. This indicates that targeting the TRIM11 mechanism could serve as a promising strategy for anti-Ferroptosis immunotherapy in asthma treatment.

Abstract Background Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9 −/− ) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9 S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. Methods To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. Results The Fgf9 S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. Conclusions Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.

Calcific aortic valve disease (CAVD) is a common cardiovascular condition in the elderly population. The aortic valve, influenced by factors such as endothelial dysfunction, inflammation, oxidative stress, lipid metabolism disorders, calcium deposition, and extracellular matrix remodeling, undergoes fibrosis and calcification, ultimately leading to stenosis. In recent years, long non-coding RNAs (lncRNAs) have emerged as significant regulators of gene expression, playing crucial roles in the occurrence and progression of various diseases. Research has shown that lncRNAs participate in the pathological process underlying CAVD by regulating osteogenic differentiation and inflammatory response of valve interstitial cells. Specifically, lncRNAs, such as H19, MALAT1, and TUG1, are closely associated with CAVD. Some lncRNAs can act as miRNA sponges, form complex regulatory networks, and modulate the expression of calcification-related genes. In brief, this review discusses the mechanisms and potential therapeutic targets of lncRNAs in CAVD.

Gasoline vehicles (GVs) have become one of the main emission sources of NOx and volatile organic compounds (VOCs) in Beijing, and determining the pollutant emission levels of in-use GVs is crucial. In this study, we assessed the emission levels, exceedance rates, and factors influencing primary air pollutants (NO, CO, and hydrocarbons (HCs) from GVs, including 7.46 million GVs in Beijing from 2019 to 2023. We predicted the variation in the exceedance rate after implementing the standard b-limit and assessed the social stability risk. In general, the emissions of GVs in Beijing were relatively low. According to the simple driving mode conditions, the CO, HC and NO concentrations in the top 50% of the cumulative probability distributions of emissions were 0.04%, 10.3 ppm and 77.0 ppm, respectively, which account for only 1/10∼1/8 of the standard a-limit values. However, we found that the pollutant concentrations corresponding to the top 10% and 90% of the cumulative probability distributions significantly differed. For example, the NO concentrations in the top 10% were 220 times greater than those in the top 90%, namely, approximately 36.5% greater than the standard limit. The greater risk of exceeding the standards was related to the occurrence of carbon deposits on the valves and cylinder heads of engines, of which medium-duty trucks (MDTs) exhibited the highest rate of exceeding the standards (34.5%) due to vehicle deterioration under high-intensity use. GVs exhibited the highest exceedance rate among all the vehicle types, at 38.7%, whereas China VI vehicles exhibited an exceedance rate of only 0.2%. If the more stringent standard b-limit were implemented, the number of vehicles exceeding the standard would increase, and the exceedance rate of GVs under the standard b-limit would be slightly greater than that under the a-limit. Overall, the exceedance rate showed a decreasing trend with increasing emission stage, with the proportion of the exceedance rate at the different emission stages also varying.

BackgroundThe roles of preoperative serum carcinoembryonic antigen (sCEA) and postoperative tissue carcinoembryonic antigen (tCEA) have been extensively studied in isolation in colorectal cancer (CRC). However, the combined role of sCEA and tCEA remains inadequately described.MethodsA total of 1,757 retrospective cases of stage 0–IV CRC from January 2006 to January 2016 in our institution were included. Clinicopathological features and follow-up data were collected. Stage 0 was combined with stage I. sCEA levels were classified as normal or high (>10 ng/mL), while tCEA levels were categorised into three grades (+, ++, and +++). This resulted in six combined groups (2 × 3). ANOVA and cross-tabulation were employed to analyse continuous and categorical data, respectively. Univariate and multivariate analyses were conducted using Cox regression. All data were analysed using SPSS 27 and R 4.3.1.ResultsSome clinicopathologic features differed significantly among the combined CEA test groups (all p 0.05) but were significant in stages III–IV (all p

Alfalfa (Medicago sativa L.) establishment is an effective strategy for grassland reconstruction in degraded ecosystems. However, the mechanisms underlying vegetation succession in reconstructed grasslands following alfalfa establishment remain elusive. In this study, we investigated vegetation community, soil quality and rhizosphere microbiota dynamics across a reconstructed grassland chronosequence in the loess region of Northwest China. A space-for-time substitution method was used to evaluate grassland vegetation coverage and alfalfa production performance in nine stands of different ages (1–50 years old). High-throughput sequencing was conducted to characterise rhizosphere microbial communities associated with alfalfa. The plant heights, yields and stem-to-leaf ratios of alfalfa all peaked in the 7-year-old stand and then decreased in older stands, with Stipa bungeana replacing alfalfa as the dominant species in the 50-year-old stand. Soil bulk density and major nutrient contents were highest in the artificial grassland (1–10 years). Soil enzyme activities (e.g., urease and sucrase) were enhanced in the transitional grassland (10–30 years), accompanied by enrichment of potentially beneficial microbial taxa (e.g., Actinobacteria and Mortierella) and functional fungi (e.g., saprotrophs and symbiotrophs) in the rhizosphere. Soil water content, total porosity and rhizosphere microbial diversity reached their maximum levels in the natural grassland (>30 years). The results indicate that alfalfa establishment alters soil structure and nutrient status in the short term, creating an optimal rhizosphere micro-environment. The improved soil conditions and rhizosphere microbiota are favourable for subsequent establishment of native grass species, leading to the formation of a stable semi-natural grasslands.

Palliative therapy utilizing interventional stents, such as vascular stents, biliary stents, esophageal stents, and other stents, has been a prevalent clinical strategy for treating duct narrowing and partial blockage. However, stent restenosis after implantation usually significantly compromises therapeutic efficacy and patient safety. Clinically, vascular stent restenosis is primarily attributed to endothelial hyperplasia and coagulation, while the risk of biliary stent occlusion is heightened by bacterial adhesion and bile sludge accumulation. Similarly, granulation tissue hyperplasia leads to tracheal stent restenosis. To address these issues, surface modifications of stents are extensively adopted as effective strategies to reduce the probability of restenosis and extend their functional lifespan. Applying coatings is one of the technical routes involving a complex selection of materials, drug loading capacities, release rates, and other factors. This paper provides an extensive overview of state of the art drug-coated stents, addressing both challenges and future prospects in this domain. We aim to contribute positively to the ongoing development and potential clinical applications of drug-coated stents in interventional therapy.

Considerable biological decline of continuously cropped alfalfa may be tightly linked to rhizosphere metabolism. However, plant-soil feedbacks and age-related metabolic changes in alfalfa stands remain unexplored. The aim of this study was to identify the linkages of rhizosphere and root metabolites, particularly autotoxins and prebiotics, to alfalfa decline under continuous cropping. We performed liquid chromatography–mass spectrometry for non-targeted metabolomic profiling of rhizosphere soils and alfalfa roots in 2- and 6-year-old stands. Differentially abundant metabolites that responded to stand age and associated metabolic pathways were identified. Compared with bulk soils, rhizosphere soils were enriched with more triterpenoid saponins (e.g., medicagenic acid glycosides), which showed inhibitory effects on seed germination and seedling growth. These autotoxic metabolites were accumulated in the old stand age, and their relative abundances were negatively correlated with plant growth, yield, and quality traits, as well as soil total nitrogen and alkali-hydrolyzable nitrogen concentrations. In contrast, prebiotic metabolites, represented by glycerolipids (e.g., glycerophosphocholine) and fatty acyls (e.g., colnelenic acid), were depleted in rhizosphere soils in the old stand. The relative abundances of glycerolipids and fatty acyls were positively correlated with plant traits and soil available phosphorus and alkali-hydrolyzable nitrogen concentrations. Age-induced changes in the rhizosphere metabolome mirrored the reprogramming patterns of root metabolome. The pathways of terpenoid backbone biosynthesis and plant hormone signal transduction, as well as metabolism of galactose, glycerophospholipid, and ɑ-linolenic acid in alfalfa roots were affected by stand age. The upregulation of terpenoid backbone biosynthesis in alfalfa roots of old plants, which stimulated triterpenoid saponin biosynthesis and exudation. Rhizosphere accumulation of autotoxins was accompanied by depletion of prebiotics, leading to soil degradation and exacerbating alfalfa decline. This research aids in the development of prebiotics to prevent and manage continuous cropping obstacles in alfalfa.

Mucormycosis caused by Cunninghamella bertholletiae (C. bertholletiae) is a rare opportunistic infection in patients with hematological malignancies (HM), with high mortality rates. Herein, we first report a case of pulmonary mucormycosis (PM) with C. bertholletiae in a 25-year-old male recently diagnosed with T-lymphoblastic lymphoma (T-LBL). The diagnosis was established through chest computed tomography (CT), metagenomic next-generation sequencing (mNGS) of blood and bronchoalveolar lavage fluid (BALF), as well as histopathological examination. Hematoxylin and eosin (HE) staining of the surgical specimen revealed the presence of fungal hyphae. He was effectively treated with liposomal amphotericin B (L-AmB) and posaconazole enteric-coated tablets, followed by aggressive surgical debridement. In our case, the fungal infection was initially identified as C. bertholletiae using mNGS, which facilitated rapid and accurate diagnosis, enabling clinicians to initiate early intensive treatment. The case also emphasizes the importance of surgical debridement in addressing affected tissues and underscores the significance of a multidisciplinary approach in implementing this treatment strategy.

Background: The procedure of catheter ablation is frequently utilized in the treatment of atrial fibrillation, and it is important to note that the mental well-being of patients who are about to undergo this procedure is typically stable. The purpose of this study is to assess the current state and influencing factors of anxiety and depression among patients with atrial fibrillation prior to undergoing catheter ablation, to offer valuable insights to clinical interventions and patient care. Methods: This study included patients with atrial fibrillation who were treated by radiofrequency ablation in a tertiary hospital in Suzhou, China from February 1 to August 31, 2023. Hospital Anxiety and Depression Scale (HADS) was used to investigate the anxiety and depression in patients with atrial fibrillation. Correlation and multivariate logistic regression analysis were performed to analyze the influencing factors of anxiety and depression. Results: 164 patients with atrial fibrillation were included. The prevalence of HADS test results indicating the presence of anxiety (HADS-A ≥ 8) was 34.15 % (56/164), the presence of depressive symptoms (HADS‐D ≥ 8) was 25.61 % (42/164). Multivariate logistic regression analysis indicated that per capita monthly household income (OR = 2.96, 95%CI: 2.61–3.48), course of atrial fibrillation (OR = 2.03, 95%CI: 1.87–2.80), the number of episodes of atrial fibrillation in the past month (OR = 1.90, 95%CI: 1.26–2.42), duration of atrial fibrillation attack in the past month (OR = 2.51, 95%CI: 1.99–3.37) were the influencing factors of anxiety (all P 0.05). Age (OR = 2.17, 95%CI: 1.67–2.96), course of atrial fibrillation (OR = 1.82, 95%CI: 1.41–2.06), duration of atrial fibrillation attack in the past month (OR = 2.57, 95%CI: 2.06–3.01) were the independent influencing factors of depression (all P

Fabricating heterojunctions with precisely controlled interfacial structures is crucial for exploring novel low-dimensional physics and for realizing high-performance devices. However, such capabilities are often constrained by contamination from the ambient environment or by the limitations of applicable methods and materials under vacuum conditions. In this study, MoS2/Au(111) heterostructures were fabricated by exfoliating MoS2 thin layers onto a crystallized Au(111) surface using a gold-assisted exfoliation method in an ultra-high vacuum environment. This method yields millimeter-sized monolayer or sub-millimeter-sized bilayers with contamination-free interfaces, which are unattainable for samples made in air. Scanning tunneling microscopy revealed that both the monolayer and the bilayer exhibit uniform and well-ordered moiré superlattices controlled by the twisting angle between the Au(111) surface and the MoS2 overlayer. The direct contact with the Au surface renders the monolayer MoS2 weakly metallic, while a less coupled bilayer is semiconducting, indicating a 0.54 eV Schottky barrier for the MoS2/Au(111) contact. This method is applicable to various combinations of van der Waals materials and metal surfaces. The uniform and controllable heterojunctions can serve as ideal model systems for exploring semiconductor–metal interfaces and atomic structures formed within.

Objectives Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological disorder. Early differentiation between TTP and primary immune thrombocytopenia (ITP) accompanied by anemia is crucial to initiate an appropriate therapeutic strategy. The objective of this study was to evaluate the predictive value of red blood cell lifespan (RBCLS), determined using the carbon monoxide breath test, in the differential diagnosis of these two diseases.Methods We conducted a retrospective analysis of 23 patients with TTP and 32 patients with ITP accompanied by anemia. RBCLS measurements were compared and evaluated between these two patient groups.Results TTP patients had a significantly shorter mean RBCLS (20 ± 8 days) than patients with ITP accompanied by anemia (77 ± 22 days, P

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108–1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355–48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228–6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051–1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484–5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006–0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

Abstract Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = $$\frac{\text{x}-{\mu }}{\alpha }$$ ), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model. Results The cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001). Conclusions The 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy. Trial registration Retrospectively registered.

Abstract Since 2017, immune checkpoint inhibitors (ICIs) have been available for the treatment of advanced hepatocellular carcinoma (HCC) or unresectable HCC, but their adoption into national medical insurance programs is still limited. Cost-effectiveness evidence can help to inform treatment decisions. This systematic review aimed to provide a critical summary of economic evaluations of ICIs as a treatment for advanced HCC and identify key drivers (PROSPERO 2023: CRD42023417391). The databases used included Scopus, Web of Science, PubMed, Embase, and Cochrane Central. Economic evaluations of ICIs for the treatment of advanced HCC were included. Studies were screened by two people. Of the 898 records identified, 17 articles were included. The current evidence showed that ICIs, including atezolizumab plus bevacizumab, sintilimab plus bevacizumab/bevacizumab biosimilar, nivolumab, camrelizumab plus rivoceranib, pembrolizumab plus lenvatinib, tislelizumab, durvalumab, and cabozantinib plus atezolizumab, are probably not cost-effective in comparison with tyrosine kinase inhibitors or other ICIs. The most influential parameters were price of anticancer drugs, hazard ratios for progression-free survival and overall survival, and utility for health statest. Our review demonstrated that ICIs were not a cost-effective intervention in advanced HCC. Although ICIs can significantly enhance the survival of patients with advanced HCC, decision-makers should consider the findings of economic evaluations and affordability before adoption of new therapies.

A new type of ternesite-ye'elimite (TCSA) cement was prepared with different amounts of ternesite. The effect of the ternesite content on the mechanical properties and hydration products of cement pastes was studied. The influence of the added gypsum content on the performance of TCSA cement was also discussed. The results showed that increasing the contents of ternesite prolonged the setting times of the TCSA clinkers. Increasing the ternesite content promoted the strength development. The increase in the ternesite content caused the lower expansion of the TCSA clinkers. The formation of ettringite, stratlingite and monosulfate was observed in the hydrated clinker pastes. The amount of stratlingite and monosulfate decreased at 28 days, while the formation of ettringite continued to increase due to the hydration of ternesite. The higher added gypsum content increased the compressive strength between 1 and 28 d. However, 15% gypsum was not conducive to the strength development at later ages. In the presence of gypsum, the formation of stratlingite was not observed. A higher gypsum content favoured ettringite precipitation at 1 d, but excess gypsum hindered the ternesite hydration.

Uranium-bearing particle analysis is an important technology in the field of nuclear safeguards. In uranium-related nuclear activities, especially in the processes of uranium enrichment, uranium-bearing aerosols are unavoidable released into the environment. There are significant differences between the uranium particles formed by uranium-bearing aerosols after drying and that from nature in terms of isotopic ratio, elemental composition, and impurity composition. Therefore, we can provide a judgment basis for the monitoring of nuclear facilities and activities by analyzing the characteristic information of micrometer or submicron sized uranium-bearing particle. After nearly 30 years of development, some relatively mature methods for the analysis of uranium-bearing particles have been developed. In this review, the process of particle analysis including sample collection, preliminary screen, particle recovery, identification and localization, and measurement is briefly introduced. The advantages and disadvantages of the commonly used technical in each process are compared. At the same time, according to the different purposes of analysis, uranium-bearing particle analysis is divided into three research directions: uranium isotope analysis, morphology and elemental composition analysis, and age-dating. Recent progress of each direction is discussed. Finally, based on the progress of the research, combined with the Development and Implementation Support Program for Nuclear Verification of the IAEA, the future research direction of uranium-bearing particle analysis technology is prospected.

Abstract Purpose Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. Method We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. Results As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. Conclusion In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Background:. Pancreatic fistula after distal pancreatectomy is a common and potentially lethal complication. The optimal closure method for the pancreatic remnant during minimally invasive distal pancreatectomy (MDP) remains unclear. Methods:. Data of consecutive patients who underwent MDP in our institution between July 2018 and June 2021 were collected. The outcomes of MDP with stapler and hand-sewn closure were compared. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF) per the International Study Group of Pancreatic Surgery definition. Results:. Of the 384 patients (stapler closure, 339; hand-sewn closure, 45) enrolled, 249 developed CR-POPF (grades B and C: 242 and 7 patients, respectively). The rates of grade B and grade C POPF in the stapler group were similar to the corresponding rates in the hand-sewn group (64.6% and 1.5% vs 51.1% and 4.4%, P = .078 and P = .223, respectively). No differences between the stapler and hand-sewn groups were observed regarding the median operation time (207 vs 222 minutes, P = .139), incidence of major complications (16.5% vs 20.0%, P = .559), and mortality (0.2% vs 0%, P = 1.000). The independent risk factors of CR-POPF were abdominal abscess, prolonged operation time, and transection site (P = .004, .006, and .001, respectively). Conclusion:. The incidence and severity of CR-POPF by stapler closure of the pancreatic stump were comparable to those associated with hand-sewn closure in MDP in this retrospective cohort. Randomized controlled trials are needed to verify this finding.

ABSTRACT Background Familial hypercholesterolemia (FH) is a hereditary disease caused mainly by mutations in the gene encoding the low‐density lipoprotein receptor (LDLR). This study aimed to confirm the pathogenicity of the LDLR c.97C>T (p.Gln33Ter) mutation through in vitro functional validation and determine whether this nonsense mutation induces nonsense‐mediated mRNA decay (NMD). Methods The proband and his family were included in accordance with Chinese Expert Consensus on FH screening. The disease‐causing mutations were fund using whole‐exome sequencing and were confirmed using bidirectional Sanger sequencing. The pathogenicity of the mutation was predicted using in silico analysis. The LDLR c.97C>T (p.Gln33Ter) mutation was generated using site‐directed mutagenesis and expressed in HEK293T cells lacking endogenous LDLR expression. The effects of this alteration on LDLR expression and LDL uptake were assessed using flow cytometry, quantitative polymerase chain analysis, western blotting, and confocal laser scanning microscopy. Results The mutation that causes FH in this family was LDLR c.97C>T (p.Gln33Ter), and family members with this mutation exhibited elevated levels of low‐density lipoprotein cholesterol (LDL‐C). The cell experiment results showed that this mutation prevented the synthesis of LDLR protein and caused the cells to lose their LDL uptake ability. Conclusion LDLR c.97C>T (p.Gln33Ter) is a pathogenic FH mutation. However, this nonsense mutation did not induce NMD.

ABSTRACT Background and Aims Chronic refractory wound is a disease that seriously impairs the quality of life of patients. Negative pressure wound therapy and platelet‐rich plasma are commonly used to treat various types of wounds. Further research is necessary to explore the efficacy and safety of the combination of negative pressure wound therapy and platelet‐rich plasma in treating chronic refractory wounds. Methods PubMed, Web of Science, EMBASE, Cochrane, CINAHL, CNKI, Sino Med, and Wanfang Med Online up until March 2024 were searched(PROSPERO No. CRD42024507963). Two investigators screened literature according to inclusion and exclusion criteria, evaluated bias and certainty of evidence using RoB 2.0 and GRADE. Stata 12.0 was used to analyze the data. Results A total of 35 randomized controlled trials involving 2495 participants were included. 34 studies were assessed as having some concerns, and 1 study as having high risk in the risk of bias assessment. The results of meta‐analysis showed that effective rate (RR1.23, 95% CI [1.17, 1.30], p

The key to restoring arid and semi-arid ecosystems is maintaining soil water and organic carbon contents. Alfalfa (Medicago sativa L.) is a high-yield perennial forage crop and performs ecological functions as a drought-resistance leguminous herb. It has been widely planted for reconstruction of degraded soils in the Loess Plateau in northwestern China, but long-term planting may affect soil carbon–water coupling and lead to crop yield reduction. To maximize the benefits of reconstructed grassland, this study explored the couplings of soil water, organic carbon, and alfalfa productivity along a reconstruction chronosequence in a semi-arid area of the Loess Plateau. Space-for-time substitution approach was used to select different-aged stands of reconstructed grassland (1, 5, 7, 10, 15, 20, 30 years old). Alfalfa above-ground biomass (AGB), soil water storage (SWS), organic carbon storage (SOCS), and carbon–water coupling coordination degree (D) were measured in the 0–100 cm soil profile. Alfalfa AGB reached a peak in the 7th year, and the degradation began in the 10th year. Both SWS and SOCS varied nonlinearly with stand age. The greatest loss of SWS occurred in the 15th year (80–100 cm depth), whereas the largest increase of SOCS occurred in the 30th year (0–20 cm depth). There was a negative feedback relationship between AGB and SWS over the 30-year study period (Pearson r = −0.835, P = 0.098). AGB and SOCS initially showed a trade-off within the first 10 years (Pearson r = −0.7431, P = 0.2569), in contrast to their positive feedback in the 20–30th years (Pearson r = 0.9978, P = 0.0421). A decoupling between SWS and SOCS (D < 0.6) was observed after 12 years of alfalfa planting. For agricultural production, a greater supply of water and organic fertilizer is required from the 7th year of alfalfa planting, and reseeding may be needed around the 10th year to prolong the life of alfalfa community. Alfalfa should be planted for no more than 12 consecutive years in the study area for ecological protection.

ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

Background: Patients with gastric cancer (GC) who underwent radical surgery require long-term follow-up (usually 5 years). The purpose of this study was to explore individualized follow-up strategies for patients with GC. Methods: This is a retrospective cohort study that established a clinicopathologic database of patients who underwent gastrectomy from January 2010 to December 2020 at Ningbo No. 2 Hospital. Follow-up was performed until March 2023. The rate of new-onset recurrence of patients with GC was explored annually according to different pTNM stages, defining a recurrence rate of less than 1% as adequate follow-up time. Results: Of the 1606 patients who were eligible, the total number of patients who completed the 5- and 10-year follow-up was 1107 and 586, respectively. A total of 444 cases were diagnosed with recurrence. The recurrence rate for stage IA patients was consistently less than 1% during the follow-up time. The adequate follow-up time (the rate of new-onset recurrence less than 1%) was 5 years for stage IB and IIA patients, and 8 years for stage IIB and IIIA patients, respectively. In contrast, stage IIIB patients were always at risk of recurrence during the follow-up time (>1%). Time to a new recurrence rate for stage IIIC patients was 6 years. Conclusion: Among patients who underwent radical gastrectomy, the rate of new-onset recurrence varied among patients with different pTNM stages. This study suggests that the follow-up of GC can be individualized and refer to pTNM stage.

Abstract Cistrome‐wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome‐wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel‐based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer‐domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases.

Abstract Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug‐loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near‐infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti‐inflammatory and antibacterial properties in models of P. aeruginosa‐infected pneumonia and wounds. Hence, this light‐activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections.

Abstract Background Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8+ T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood–brain barrier disruption. However, the damage effect of CD8+ T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8+ T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8+ T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8+ T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8+ T cells through up-regulating PD-L1 induced by IFNs. Methods Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8+ T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNβ or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro. Results In vivo, ECM mice showed infiltration of activated CD8+ T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8+ T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNβ, IFNγ, or ECM CD8+ T cells in vitro. Furthermore, the IFNβ or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8+ T cell-mediated damage both in vitro and in vivo. Conclusion Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8+ T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM. Graphical Abstract

Abstract MAPK pathway-driven tumorigenesis, often induced by BRAFV600E, relies on epithelial dedifferentiation. However, how lineage differentiation events are reprogrammed remains unexplored. Here, we demonstrate that proteostatic reactivation of developmental factor, TBX3, accounts for BRAF/MAPK-mediated dedifferentiation and tumorigenesis. During embryonic development, BRAF/MAPK upregulates USP15 to stabilize TBX3, which orchestrates organogenesis by restraining differentiation. The USP15-TBX3 axis is reactivated during tumorigenesis, and Usp15 knockout prohibits BRAFV600E-driven tumor development in a Tbx3-dependent manner. Deleting Tbx3 or Usp15 leads to tumor redifferentiation, which parallels their overdifferentiation tendency during development, exemplified by disrupted thyroid folliculogenesis and elevated differentiation factors such as Tpo, Nis, Tg. The clinical relevance is highlighted in that both USP15 and TBX3 highly correlates with BRAFV600E signature and poor tumor prognosis. Thus, USP15 stabilized TBX3 represents a critical proteostatic mechanism downstream of BRAF/MAPK-directed developmental homeostasis and pathological transformation, supporting that tumorigenesis largely relies on epithelial dedifferentiation achieved via embryonic regulatory program reinitiation.

Abstract Background Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. Methods Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. Results The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115–1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003–1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003–1.461) alleles were significantly different between the control group and the case group (P

To improve the quality of jujube wine, enrich the aroma of jujube wine, and produce a soft and palatable, mellow and fragrant jujube fruit wine, the single factor experiments, neural networks, and genetic algorithms were used to optimize the fermentation process, and in vitro digestion experiments were conducted to study the digestive characteristics and antioxidant activity of banzao jujube juice and banzao fermented wine in the gastrointestinal tract. The results showed that the best ingredient was hawthorn for jujube wine production. The optimal fermentation conditions of jujube wine were the ratio of hawthorn to jujube was 1:2.96, fermentation temperature 29 ℃, extraction temperature 45 ℃. Under the optimal conditions, the sensory score of the jujube wine was 81.66. The results of in vitro digestion showed that the total phenol content, DPPH free radical scavenging rate, and ABTS+ free radical scavenging rate of jujube wine increased by 16.19%, 22.15%, and 13.09% after the end of gastric digestion, respectively, and increased by 42.06%, 22.31%, and 85.80% after the end of intestinal digestion. The study would provide a reference for the development and industrial production of jujube wine products.

This study comprehensively investigates the impact of varying red-to-blue light ratios on the growth of Spanish lettuce. The research considers various factors such as growth morphology, photosynthetic parameters, and chlorophyll fluorescence. Lettuce was cultivated in an environment with a photosynthetic photon flux density (PPFD) of 200 ± 20 μmol/m2/s and a photoperiod of 16 h per day. The experiment incorporated eight distinct light treatment methodologies, with the red-to-blue light ratios ranging from 2:8 (R2B8) to 9:1 (R9B1). The data implies that during the initial 20 days of growth, groups exposed to a higher proportion of red light demonstrated superior growth. In particular, the R9B1 group exhibited the highest increase in plant height. The photosynthetic performance of leaves (net photosynthetic rate, stomatal conductance, and transpiration rate) showed a tendency to rise with a decreasing red-to-blue ratio within a particular range, peaking at R3B7. However, both the dry matter content and fresh weight were relatively lower under the R3B7 light quality ratio. The results indicate that cultivating lettuce under the R8B2 ratio led to optimal outcomes. This group significantly outperformed the other test groups in terms of weight and exhibited higher photosynthetic rates. Despite exhibiting lower stomatal conductance, this group reduced energy consumption and ultimately achieved the highest overall weight.

Abstract Background Monkeypox is a zoonotic disease caused by the monkeypox virus and is increasingly recognized as a serious public health concern worldwide. Our aim was to investigate the knowledge and attitudes of Chinese medical students regarding monkeypox. Methods A cross-sectional study was conducted among 8,897 college students from China. An e-questionnaire was used to collect data on knowledge (17 items), attitudes (12 items), and baseline criteria. The relationships between a range of factors and knowledge and attitudes were studied using univariate and multivariate analyses. Results A total of 79.33% of the study participants were female, 89.10% were of Han ethnicity, 72.50% were from rural areas, 50.39% were in their first year, and 80.65% were medical majors. A total of 50.88% had good knowledge of monkeypox, and 57.11% had a positive attitude towards monkeypox knowledge. Univariate analysis revealed that origin and major were the factors affecting the knowledge level of monkeypox among participants. Rural students had more knowledge of monkeypox than urban students, and nonmedical students had greater awareness of monkeypox than did medical students. Moreover, sex and grade were the factors influencing participants’ attitudes towards monkeypox; men had more positive attitudes than women did, and senior students had more positive attitudes than junior students did. Multivariate analysis revealed that major and the origin of the students independently influenced the monkeypox knowledge of Chinese medical students, while sex, grade and monkeypox knowledge were significantly related to attitudes towards monkeypox. Conclusion This study revealed that nearly half of the Chinese medical students had good knowledge and a positive attitude towards monkeypox. Student origin and major independently influenced the knowledge of Chinese medical students of monkeypox, while sex, grade and knowledge were independently related to the attitudes of Chinese medical students towards monkeypox.

Abstract Background Familial hypercholesterolemia (FH) is a prevalent hereditary disease that can cause aberrant cholesterol metabolism. In this study, we confirmed that c.415G > A in low-density lipoprotein receptor (LDLR), an FH-related gene, is a pathogenic variant in FH by in silico analysis and functional experiments. Methods The proband and his family were evaluated using the diagnostic criteria of the Dutch Lipid Clinic Network. Whole-exome and Sanger sequencing were used to explore and validate FH-related variants. In silico analyses were used to evaluate the pathogenicity of the candidate variant and its impact on protein stability. Molecular and biochemical methods were performed to examine the effects of the LDLR c.415G > A variant in vitro. Results Four of six participants had a diagnosis of FH. It was estimated that the LDLR c.415G > A variant in this family was likely pathogenic. Western blotting and qPCR suggested that LDLR c.415G > A does not affect protein expression. Functional studies showed that this variant may lead to dyslipidemia by impairing the binding and absorption of LDLR to low-density lipoprotein ( LDL). Conclusion LDLR c.415G > A is a pathogenic variant in FH; it causes a significant reduction in LDLR’s capacity to bind LDL, resulting in impaired LDL uptake. These findings expand the spectrum of variants associated with FH.

Objective: To compare the impact of two pesticide dose forms on Blattella germanica (B. germanica)resistance enzymes.The micro-drop technique was utilized on subcultured B. germanica, and the metabolic enzyme activity was assessed.Using spectrophotometry, the relative enzyme activities of B.germanica were determined.Profile analysis was used to compare the enzyme activities of beta-cypermethrin in both nanoemulsion and traditional emulsion forms.Findings: The suppression percentages of the acetylcholinesterase enzyme (AchE), GST, and P450–O demethylases across different pesticide formulations were analyzed using regression equations, yielding F = 31.18, P

Abstract Mites are among the most abundant invertebrates in subsurface ecosystems, and their community assemblages and distributions are often significantly influenced by the diversity of habitat resources. The cave ecosystem encompasses drastic changes in nonbiological factors, such as changes in lighting conditions from bright to extraordinarily dark and habitat gradients of surface plant resources from abundant to scarce or even disappearing, providing an ideal unique environment for evaluating the assembly mechanism of soil animal communities. Nevertheless, there still needs to be a sufficient understanding of the biodiversity patterns and drivers of mite communities across environmental gradients in karst caves. We conducted a comprehensive survey on the composition and diversity of soil mites in three photometric zones (dark, twilight, and light) of a typical karst cave and its adjoining extractive environments (forest scrub and farmland). Our research aimed to investigate the ecological relationships of mite communities between above‐ and below‐ground habitats and the effects of abiotic factors on mite communities. We collected 49 families, 86 genera, and 1284 mites. In the external cave environment, we captured 1052 mites from 72 genera and 45 families; in the internal cave environment, we captured 232 mites from 46 genera and 29 families. The abundance, richness of genera, and diversity parameters of the mite community decreased from the cave entrance to the cave interior with decreasing light intensity. Oribatid mites dominated the mite community. Protoribates and Scheloribates were the dominant genera, along with Tectocepheus and 11 other genera, which primarily distinguished the mite communities among different habitats. Forty endemic taxa were found in the external cave environment, compared to 14 endemic taxa in the internal cave environment. The mite community showed a strong preference for the cave ecosystem habitat. Temperature, humidity, and soil nitrogen content significantly influenced the distribution pattern of mite communities (VIP > 0.8, p

Background: Bevacizumab resistance poses barriers to targeted therapy in clear cell renal cell carcinoma (ccRCC). Whether there exist epigenetic targets that modulate bevacizumab sensitivity in ccRCC remains indefinite. The focus of this study is to explore the role of UCHL1 in ccRCC. Methods: Both in vitro and in vivo experiments were utilized to investigate the roles of UCHL1 in ccRCC. In vivo ubiquitination assays were performed to validate the posttranslational modification of KDM4B by UCHL1. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were utilized to explore KDM4B/VEGFA epigenetic regulations. Results: UCHL1 was increased in ccRCC and associated with unfavorable survival outcomes in patients. UCHL1 was required for ccRCC growth and migration. Mechanistically, the wild-type UCHL1, but not C90A mutant, mediated the deubiquitination of KDM4B and thereby stabilized its proteins. KDM4B was up-regulated in ccRCC and potentiated cell growth. UCHL1 depended on KDM4B to augment ccRCC malignancies. Targeting UCHL1 suppressed tumor growth, colony formation, and migration abilities, which could be rescued by KDM4B. Furthermore, KDM4B was directly bound to the promoter region of VEGFA, abolishing repressive H3K9me3 modifications. KDM4B coordinated with HIF2α to activate VEGFA transcriptional levels. UCHL1-KDM4B axis governs VEGFA levels to sustain the angiogenesis phenotypes. Finally, a specific small-molecule inhibitor (6RK73) targeting UCHL1 remarkably inhibited ccRCC progression and further sensitized ccRCC to bevacizumab treatment. Conclusion: Overall, this study defined an epigenetic mechanism of UCHL1/KDM4B in activating VEGF signaling. The UCHL1-KDM4B axis represents a novel target for treating ccRCC and improving the efficacy of anti-angiogenesis therapy.

Background The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

The electrocatalytic conversion of CO2 (CO2RR) to multi-carbon products has been an appealing strategy to reduce carbon emissions. However, rapid experimental discovery of efficient CO2RR electrocatalysts and fast recording of full product distribution information is non-trivial. Herein, we used an electrocatalyst testing platform featuring a home-built automatic flow cell to accelerate catalysts screening. Based on 364 effective data points from 42 Cu-lanthanide bimetallic catalysts obtained within 21 working hours, we found that Eu modification over Cu can promote C2+ faradaic efficiency (FE). We have previously reported part of the screening data and the optimization of the Mg-Cu catalyst（Angew. Chem. 2022, 134, e202213423）. Here we augmented the dataset by adding the lanthanide modifiers and reported the Eu-Cu catalyst resulted from the high-throughput investigation. Our characterizations revealed that the Eu2+ reduced from Eu3+ during the catalyst synthesis prevented the agglomeration of nanoparticles, thus making europium modifications stand out from other lanthanide metal modifiers on FE C2+ enhancement. We then optimized the Eu-CuOx catalyst based on the above understanding to achieve ∼80% C2+ FE at a high current density of 1.25 A cm−2.

The use of properly designed nanostructured anode targets enables direct generation of high performance X-rays. In particular, this scheme has attracted widespread research interest for obtaining micro-focal spot X-ray radiation. In this study, we developed a thermal evaporating deposition technique and achieved controllable preparation of different single crystalline molybdenum (Mo) nanostructures by exploiting the lattice matching relationship between the substrate and the product crystal orientation. When used as an anode target for a reflective X-ray radiation device, these nanostructured Mo single crystals exhibit advantages over traditional targets at larger radiation angles. Further experimental and simulation results demonstrate the geometric characteristics of these Mo nanostructures and their correlation with the radiation intensity, focal spot size, and brightness of the generated X-rays. Among them, a unique frustum of square pyramid single crystalline Mo nanostructure stands out, due to its combination of three-dimensional body feature of nanostructures and radiation plane feature of planar targets. The research results not only provide a class of nanostructured anode target materials for reflective X-ray sources with different radiation angle requirements, but also make it possible to design and develop miniaturized devices for X-ray sources with selectable radiation performance and micro-focal spot.

Electroacupuncture pretreatment is considered as an optimal strategy for inducing cerebral ischaemic tolerance. However, the underlying neuroprotective mechanism of this approach has never been explored from the perspective of calcium homeostasis. Intracellular calcium overload is a key inducer of cascade neuronal injury in the early stage after cerebral ischaemia attack and the Na+/Ca2+ exchanger (NCX) is the main plasma membrane calcium extrusion pathway maintaining post-ischaemic calcium homeostasis. This study aims to investigate whether the regulation of NCX-mediated calcium transport contributes to the cerebroprotective effect of electroacupuncture pretreatment against ischaemic injury and to elucidate the underlying mechanisms involved in this process. Following five days of repeated electroacupuncture stimulation on Baihui (GV20), Neiguan (PC6), and Sanyinjiao (SP6) acupoints in rats, in vivo and in vitro models of cerebral ischaemia were induced through middle cerebral artery occlusion and oxygen/glucose deprivation (OGD), respectively. Firstly, we verified the neuroprotective effect of electroacupuncture pretreatment from the perspective of neurological score, infarct volume and neuronal apoptosis. Our findings from brain slice patch-clamp indicated that electroacupuncture pretreatment enhanced the Ca2+ efflux capacity of NCX after OGD. NCX1 expression in the ischaemic penumbra exhibited a consistent decline from 1 to 24 h in MCAO rats. Electroacupuncture pretreatment upregulated the expression of NCX1, especially at 24 h, and silencing NCX1 by short hairpin RNA (shRNA) administration reversed the protective effect of electroacupuncture pretreatment against cerebral ischaemic injury. Furthermore, we administered LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, prior to inducing ischaemia to investigate the upstream regulatory mechanism of electroacupuncture pretreatment on NCX1 expression. Electroacupuncture pretreatment activates PI3K/Akt pathway, leading to an increase in the expression of NCX1, which facilitates calcium extrusion and exerts a neuroprotective effect against cerebral ischaemia. These findings provided a novel insight into the prevention of ischemic stroke and other similar conditions characterized by brain ischaemia or hypoperfusion.

Utilizing data of Doppler wind lidar and L-band radiosonde system installed at Qingdao National Basic Meteorological Observing Station from April 2021 to December 2022, their detection capability and accuracy under low visibility weather conditions are compared and evaluated, specifically in terms of detection height, horizontal wind speed and wind direction, using data obtained from L-band radiosonde system as the reference standard. During non-precipitation weather, when visibility exceeds 10000 m, the wind lidar demonstrates a stable average maximum detection height of approximately 1200 m. The root mean square errors of the wind speed and direction fluctuate around 1.2 m·s-1 and 25°, respectively. However, when the visibility drops below 10000 m, the detection height and accuracy of the wind lidar are influenced by the level of interference, particularly in different visibility and relative humidity ranges. In situations where visibility is below 1000 m, the decrease in atmospheric visibility is attributed to increased water vapor content in the air, with relative humidity consistently exceeding 95%. This high humidity significantly interferes with laser transmission in the atmosphere, resulting in an average maximum detection height of less than 400 m. The correlation between horizontal wind speed and direction decreases to 0.91 and 0.94, and the root mean square error increases to 1.4 m·s-1and 42.7°, respectively. When the visibility ranges between 1000 m and 10000 m, the wind lidar's detection capability varies with the water vapor content in the atmosphere. In cases where relative humidity is below 90%, meeting the criteria for hazy days, the decrease in atmospheric visibility is primarily due to increased aerosol particle content. Under these conditions, the average maximum detection height remains stable above 1200 m. The correlation coefficients for horizontal wind speed and direction are as high as 0.97 and 0.98, with root mean square errors of about 1.1 m·s-1 and 22.3°, respectively. These results are comparable to the detection capability demonstrated under high visibility weather conditions. As relative humidity increases, the impact of water vapor attenuation on laser transmission starts to affect the detection height and accuracy of the wind lidar to varying degrees. When the relative humidity exceeds 95%, the average maximum detection height influenced by water vapor decreases to below 400 m. The correlation coefficient of wind speed decreases to 0.94, with a corresponding increase in the root mean square error to 1.5 m·s-1, and the accuracy of wind direction remains relatively stable under these conditions.

The relentless pursuit of miniaturization in the field of photonics has led to the emergence of micro–nano optical devices as a cornerstone of modern technology [...]

The assessment of trafficability for planetary rovers in relation to non-geometric hazards is a crucial issue in deep space exploration. This study relies on terramechanics theory and incorporates actual data from Mars soil and rover parameters to develop a model that accurately represents the interaction between the rover’s wheels and Martian soil. Through numerical simulations, this model specifically investigates the relationship between the current of the rover’s wheel drive motor and factors such as slip ratio, soil pressure parameters, and soil shear parameters. Terrestrial experiments are also conducted to verify the precision of certain numerical calculations. The proposed wheel–soil interaction model, based on wheel motor current, provides a foundation for assessing non-geometric trafficability and the inversion of planetary soil parameters.

With the marine industry’s demands for carbon reduction and increased reliability, the friction and wear performance of marine engines is becoming increasingly important. MAX phase materials show great potential in marine engine tribopair materials due to their unique microstructure and performance. The typical MAX phase material Ti3AlC2 was combined with MoDTC and added to the lubricant containing ZDDP additive for the tribopair composed of chromium-based ceramic composite coated steel (CKS) piston rings and cast iron cylinder liners under impact-sliding conditions. Compared to Ti3AlC2 alone, the friction coefficient and wear depth of the designed composite additive MoDTC/Ti3AlC2 were reduced by 36.9% and 41.4%, respectively. The worn surface lubricated with the Ti3AlC2/MoDTC composite additive showed fewer scratches with significantly less plastic deformation and clearer honing grooves. The multi-component tribofilm containing FeS, MoS2, MoO3, ZnO, TiO2, Al2O3, unoxidised particles, short-chain phosphates, and some ZnS was present on the worn cylinder liner surface. The synergistic effect of Ti3AlC2, MoDTC and ZDDP additives in the lubricant can isolate the mutual contact, generate a solid tribofilm and reduce the scratching. This can provide some guidance for the development of high-performance lubricant additives under impact-sliding conditions.