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Abstract Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium ulcerans, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on Mycobacterium marinum, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 M. marinum strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clusters. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of M. marinum's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for M. tuberculosis and other mycobacteria.

Abstract Background The benefits of low-pressure laparoscopic cholecystectomy (LPLC) in patients with cardiopulmonary comorbidities remain unclear. This study aimed to explore the feasibility and pulmonary effects of LPLC in patients with cardiopulmonary comorbidities. Methods This was a multicenter, parallel, double-blind, randomized controlled trial. Eligible patients included patients with cardiac or pulmonary comorbidities, who were randomly assigned (1:1) to undergo LPLC (10 mmHg) or standard-pressure laparoscopic cholecystectomy (SPLC) (14 mmHg). The primary outcome was postoperative partial pressure of carbon dioxide (CO2). Surgical safety variables, patient recovery, pulmonary function parameters, and surgeon comfort were also compared between groups. Results This study enrolled 144 participants, with 124 participants extracted for the final analysis (62 in LPLC and 62 in SPLC group, respectively). The median postoperative PaCO2 was similar in the LPLC (43.3 mmHg) and SPLC (43.0 mmHg) groups (p = 0.988). Pulmonary parameters including postoperative pH, PaCO2, HCO3, and lactate levels were similar between the two groups. Postoperative base excess was significantly higher in the LPLC group (− 0.6 mmol/L [− 6.9 ~ 7.5] vs. −1.9 mmol/L [− 6.6 ~ 5.4]; p = 0.031). There was no between-group difference regarding intraabdominal operative time, rate of intraoperative bile spillage, blood loss, surgeon comfort during surgery, and conversion rate. Moreover, postoperative major complication rates, the median time to the first flatus, postoperative hospital stay, or mean postoperative visual analog scale score for pain were similar in both groups. Conclusions This study found no reduction of partial pressure of CO2 with LPLC compared with SPLC for patients with cardiopulmonary comorbidities. LPLC with a pneumoperitoneum pressure of 10 mmHg may be safe and feasible for these patients when performed by experienced surgeons, although it does not improve pulmonary parameters. Registration The trial is retrospectively registered at ClinicalTrials.gov (NCT04670952) on December 17, 2020.

Abstract Background The triglyceride-glucose (TyG) index is a reliable marker of insulin resistance that is involved in the progression of hypertension. This study aimed to evaluate the association of the TyG index with the risk for major cardiovascular events (MACE) in young adult hypertension. Methods A total of 2,651 hypertensive patients aged 18–40 years were consecutively enrolled in this study. The TyG index was calculated as Ln [triglycerides × fasting plasma glucose/2]. The cutoff value for an elevated TyG index was determined to be 8.43 by receiver-operating characteristic curve analysis. The primary endpoint was MACE, which was a composite of all-cause death, non-fatal myocardial infarction, coronary revascularization, non-fatal stroke, and end-stage renal dysfunction. The secondary endpoints were individual MACE components. Results During the median follow-up time of 2.6 years, an elevated TyG index was associated with markedly increased risk of MACE (adjusted hazard ratio [HR] 3.440, P

Abstract This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan–Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146–4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291–4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028–3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006–2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193–4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

Abstract Objective The aim of this study is to evaluate the clinical efficacy of injectable cemented hollow pedicle screw (CICPS) in the treatment of osteoporotic lumbar degenerative diseases through a large sample long-term follow-up study. Additionally, we aim to explore the risk factors affecting interbody fusion. Methods A total of 98 patients who underwent CICPS for transforaminal lumbar interbody fusion (TLIF) for osteoporotic lumbar degenerative disease from March 2011 to September 2017 were analyzed. X-ray and electronic computed tomography (CT) imaging data were collected during preoperative, postoperative, and follow-up periods. The data included changes in intervertebral space height (ΔH), screw failure, cement leakage (CL), and intervertebral fusion. The patients were divided into two groups based on their fusion status one year after surgery: satisfied group A and dissatisfied group B. Surgical data such as operation time, intraoperative bleeding volume and surgical complications were recorded, and visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the improvement of lumbar and leg pain. Results The mean follow-up time was 101.29 months (ranging from 70 to 128 months). A total of 320 CICPS were used, with 26 screws (8.13%) leaking, 3 screws (0.94%) experiencing cement augmentation failure, and 1 screw (0.31%) becoming loose and breaking. The remaining screws were not loose or pulled out. Female gender, decreased bone density, and CL were identified as risk factors affecting interbody fusion (P

Abstract The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

Abstract Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998–2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED’s monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944–0.995), Bias (−0.68-0.53), and Root Mean Square Error (5.50–15.59 mm). Additionally, TPRED’s monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED’s annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

Abstract The ankle joint, which connects the lower limbs and the sole of the foot, is prone to sprain during walking and sports, which leads to ankle arthritis. Supratroleolar osteotomy is an ankle preserving operation for the treatment of ankle arthritis, in which the osteotomy is an important fixing and supporting part. In order to avoid stress shielding effect as much as possible, the osteotomy block is designed as a porous structure. In this study, the osteotomy block was designed based on three-period minimal surface, and the designed structure was manufactured by 3D printing. The mechanical properties of different structures were studied by mechanical test and finite element simulation. In mechanical tests, the Gyroid structure showed a progressive failure mechanism from bottom to bottom, while the Diamond structure showed a shear failure zone at 45° Angle, which was not conducive to energy absorption and was more prone to brittle fracture than the Gyroid structure. Therefore, the Gyroid structure is valuable for further research in the development of porous osteotomy.

Abstract In recent years, the exploration of seabed has been intensified, but the submarine soils of silt and sand in the Yellow Sea area have not been well investigated so far. In this study, the physical and mechanical properties of silt and sand from the Yellow Sea were measured using a direct shear apparatus and their microstructures were observed using a scanning electron microscope. The test results suggest that the shear strength of silt and sand increases linearly with the increase of normal stress. Based on the direct shear test, the scanning electron microscope was used to observe the section surface of sand. It is observed that the section surface becomes rough, with many “V”‐shaped cracks. Many particles appear on the surface of the silt structure and tend to be disintegrated. The X‐ray diffraction experiment reveals that the sand and silt have different compositions. The shear strength of sand is slightly greater than that of silt under high stress, which is related to the shape of soil particles and the mineral composition. These results can be a reference for further study of other soils in the Yellow Sea; meanwhile, they can serve as soil parameters for the stability and durability analyses of offshore infrastructure construction.

IntroductionIn recent years, China has been carrying out the Diagnosis Related Groups (DRGs) payment reform, which has an impact not only on payment methods and medical expenses, but also on the behaviors of medical staff. Some of these behaviors are unexpected by policymakers, such as turning away critically ill patients, disaggregating hospitalization costs, setting up disease groups with higher points, and so on. This phenomenon attracted the attention of some scholars, who put forward a few positive intervention measures, mainly including policy advocacy and system improvement. The scholars believed that the former was more feasible. However, there is a lack of research on the effects and influencing processes of these interventions. Therefore, this study aims to explore the influence of policy advocacy and education on medical staff’s adaptation to DRGs payment reform in China and the role of policy cognition in this process, in order to provide experiences for the smooth implementation and sustainable development of DRGs payment system.MethodsA questionnaire survey was conducted among 650 medical staff in five large general hospitals in Zhejiang Province, China, to understand their participation and feedback on policy advocacy and education, their adaptation to the current DRGs payment reform, and their cognition of relevant policies. After descriptive statistical analysis, partial correlation analysis, multiple linear regression models and bias correction Bootstrap sampling method were used to analyze the mediating effect of policy cognition factors.ResultsAll respondents had participated in organized collective policy advocacy and education activities in the past year, but the degree of satisfaction and recognition was not very high. 59.5 percent said their adaptation to the DRGs payment reform was average. Nearly half did not regularly pay attention to and participate in the management of the medical costs of patients with DRGs through compliance. And they had a low understanding of the specific rules of DRGs payment and did not form a high policy identity. The mediating effect values of policy cognition were 0.148, 0.152, 0.108, and 0.057, respectively, when the frequency and quality of policy advocacy and education influenced medical staff’s adaptive perception and adaptive behaviors.DiscussionThe organized collective policy advocacy and education can promote medical staff’s adaptation to DRGs payment reform by improving their policy cognition, and the action paths are diverse. Policymakers and hospital managers need pay attention to this phenomenon, and formulate demand-centered, value-oriented whole-process advocacy and education strategies while constantly improving the DRGs payment system. All of these provided a basis for further research and practice of positive intervention in DRGs payment reform.

Introduction Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF.Methods/analysis This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments.Ethics and disseminationapproval The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences.Trial registration number NCT05610215.

Identification of unique essential bacterial genes is important for not only the understanding of their cell biology but also the development of new antimicrobials. Here, we report a previously unrecognized core component of the Acinetobacter baumannii divisome. Our results reveal that the protein, termed Aeg1 interacts with multiple cell division proteins, including FtsN, which is required for components of the divisome to localize to the midcell. We demonstrate that the FtsAE202K and FtsBE65A mutants effectively bypassed the need of Aeg1 by A. baumannii, as did the activation variants FtsWM254I and FtsWS274G. Our results suggest that Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI. The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents.

Legionella infection, the causative agent of Legionnaires’ disease, represents a significant threat to human health. The pathogenesis of this infection is intricately linked to the complex interactions between the bacterium and its host, resulting in profound metabolic perturbations. Central to these metabolic shifts is the bacterium’s modulation of lipid metabolism, with changes in lipid synthesis and breakdown modifying membrane composition and function. These alterations can influence cellular signaling and immune responses, further contributing to disease progression. It also disrupts glucose utilization and lipid metabolism, altering cellular energy production and immune responses. Additionally, Legionella infection perturbs amino acid and protein metabolism, affecting protein synthesis and degradation, leading to changes in cellular functions and immune responses. This mini-review underscores the complexity of metabolic perturbations in Legionella infection and their significance in host-pathogen interactions. Understanding these metabolic shifts provides valuable insights into the pathogenesis of Legionnaires’ disease and could lead to the development of novel therapeutic strategies.

The S(IV)–Fe(II)/PM pretreatment has demonstrated preliminary potential as an effective ultrafiltration (UF) pretreatment technology. However, a comprehensive understanding of its impact on UF membrane fouling control and the dynamic evolution of membrane fouling during prolonged operation is still lacking. In this study, a relatively prolonged fouling experiment was conducted. Results revealed that the S(IV)–Fe(II)/PM pretreatment exhibited superior performance over Al(III) coagulation pretreatment in mitigating the transmembrane pressure difference and addressing both reversible and irreversible membrane fouling. The application of a cluster analysis method to classify membrane fouling evolution stages further confirmed that S(IV)–Fe(II)/PM pretreatment effectively decelerated the rate of membrane fouling evolution. The surface cake layer of UF membranes pretreated with S(IV)–Fe(II)/PM exhibited greater looseness and smoothness. It also showed better results than Al(III) coagulation pretreatment in reducing the accumulation of organic foulants, controlling the Si content and reducing the total microorganisms and live microorganisms in the UF feed water. Variance Partitioning Analysis indicated that the combined contribution of organic, inorganic, and biological foulants was the most significant for UF membranes after S(IV)–Fe(II)/PM pretreatment (50.4%) and UF membranes after Al(III) coagulation pretreatment (70.2%). These findings underscore the efficacy of S(IV)–Fe(II)/PM pretreatment in controlling UF membrane fouling under prolonged operation. HIGHLIGHTS S(IV)/Fe(II)/PM pretreatment efficiently mitigated UF membrane fouling during long-term operation.; S(IV)/Fe(II)/PM pretreatment yielded a long uncontaminated stage and accelerated contaminated stage.; S(IV)/Fe(II)/PM pretreatment suppressed the contribution of organic–inorganic–biological composite fouling.;

Abstract Aims Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). Methods A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. Results During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160–2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. Conclusions The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Abstract Since the 20th century, the temperature on the Qinghai–Tibetan Plateau (QTP) has increased at a rate of 2–3 times that of global warming. Consequently, the soil temperature and active layer thickness have also increased, which have directly caused severe degradation of the frozen ground on the QTP. Using a hydrological model driven by climate and vegetation forcing, the spatial and temporal changes in the hydrothermal characteristics of the Upper Yellow River Basin (UYRB) from 1960 to 2019 were modeled and the mechanism of the changes was analyzed. During the past six decades, the soil temperature in the UYRB exhibited an increasing trend. The degradation of permafrost in the UYRB was accompanied by thickening of the active layer, a reduction of the maximum depth of the seasonal frost penetration, and continuous extension of the basin thawing time. This degradation was also associated with the increase in the soil moisture content and decrease in the soil ice content, resulting in degradation of the permafrost area by one-tenth of the total area in the UYRB. The reduction of the permafrost area and the thickening of the active layer can profoundly impact hydrological processes and ecosystems. These findings play a critical role in designing efficient strategies to manage and protect frozen ground and serve as a valuable reference for understanding the consequences of frozen ground degradation globally.

Abstract Environmental regulations are important means to influence manufacturing enterprise green development. However, there are two completely different conclusions both in theoretical and in empirical research, namely the “Follow Cost” theory and the “Porter Hypothesis”. The nonlinear mechanism needs to be considered. Therefore, this study aims to explain the threshold impact of heterogeneous environmental regulations on enterprise green total factor productivity. Environmental regulations are divided into different sub-categories, then based on the panel data of 1220 Chinese manufacturing listed companies from 2011 to 2020, this paper uses threshold regression model to examine the impact of heterogeneous environmental regulations on Chinese manufacturing enterprise Green Total Factor Productivity. The empirical results show that: (1) Command-controlled, market-incentive and voluntary-agreement environmental regulation all have a significant nonlinear impact on enterprise Green Total Factor Productivity. (2) Enterprise R&D investment plays a threshold role in the impact. (3) There are industry and equity type differences in the impact process. This study focuses on the micro level of enterprises and tests the threshold mechanism, which make some theoretical complement to previous researches. The research results are not only beneficial for the government to propose appropriate environmental regulatory policies, but also for enterprises to achieve green growth through heterogeneous R&D investment.

Accurate landslide susceptibility mapping (LSM) relies on a detailed landslide inventory and relevant influencing factors. In this study, Sentinel 2 remote sensing imagery is employed to establish a comprehensive landslide inventory leveraging attention U-Net backbone networks in Zhangjiajie City of Hunan Province, China. Subsequently, the refined landslide inventory, with more precise boundaries, is integrated into LSM process. A multi-scale sampling three-dimensional convolutional neural network (3D-CNN) is introduced into LSM, facilitating the extraction of multi-scale neighbourhood characteristics and deep information of relevant topographical, hydrological, meteorological, geological, and human activity factors. Experimental results demonstrate that this method achieves the highest accuracy and area under the receiver operating characteristic (ROC) curve. Moreover, its recall and F1-score significantly higher surpass those of other small-, medium-, and large-scale models, with the F1-score being more than 10% higher. This superior performance is attributed to its proficiency in discerning the nonlinear spatial correlation between landslide occurrences and influencing factors. The comprehensive consideration of scale characteristics through the multi-scale sampling strategy outperforms the single-scale CNN models across all evaluation metrics. This study furnishes a suite of high-precision methodologies for landslide hazard assessment in Zhangjiajie City, thereby offering invaluable support to decision-makers engaged in large-scale land use planning and geologic disaster prevention.

Background The potential impact of elevated intra-abdominal pressure (IAP) on residual renal function (RRF) has not been determined. The objective of this study was to investigate the relationship between IAP and the rate of RRF decline in newly initiated peritoneal dialysis (PD) patients, and to identify the optimal IAP threshold value for delaying the deterioration of RRF.Methods A cohort of 62 newly initiated PD patients who completed both 6- and 12-month follow-up evaluations was obtained using the Durand method. A logistic regression model was used to identify variables associated with a rapid decline in RRF. Receiver operating characteristic (ROC) curves were generated to determine the optimal threshold value. Another retrospective cohort analysis was performed to validate the identified critical value.Results For each 1 cmH2O increase in IAP, the risk of a rapid decline in the RRF increased by a factor of 1.679. Subsequent analysis revealed that patients in the high IAP group had more significant decreases in residual renal estimated glomerular filtration rate (eGFR) (Z = −3.694, p

This study begins by discussing Internet of Things (IoT) technology and analyzing the classification of street space into four types, along with the Green Looking Ratio (GLR). Following this, the Fully Convolutional Network (FCN)-8s framework is employed to construct a street view image semantic segmentation model based on FCN principles. Subsequently, IoT technology is utilized to analyze the proportion of GLR and satisfaction in the street space within the historical urban area of T City. The findings reveal a significant positive correlation (significance level p

Background: Aged sarcopenia is characterized by loss of skeletal muscle mass and strength, and mitochondrial dysregulation in skeletal myocyte is considered as a major factor. Here, we aimed to analyze the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on mitochondrial reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in aged skeletal muscles. Methods: C2C12 cells were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of cellular ROS, mitochondrial ROS, and expression of PGC-1α and Nrf2. Different PGC-1α expression in cells was established by transfection with small interfering RNA (siRNA) or plasmids overexpressing PGC-1α (pEX-3-PGC-1α). The effects of different PGC-1α expression on cellular ROS, mitochondrial ROS and Nrf2 expression were measured in cells. Wild type (WT) mice and PGC-1α conditional knockout (CKO) mice were used to analyze the effects of PGC-1α on aged sarcopenia and expression of Nrf2 and CD38 in gastrocnemius muscles. Diethylmaleate, a Nrf2 activator, was used to analyze the connection between PGC-1α and Nrf2 in cells and in mice. Results: In C2C12 cells, the expressions of PGC-1α and Nrf2 were declined by the 7β-OHC treatment or PGC-1α silence. Moreover, PGC-1α silence increased the harmful ROS and decreased the Nrf2 protein expression in the 7β-OHC-treated cells. PGC-1α overexpression decreased the harmful ROS and increased the Nrf2 protein expression in the 7β-OHC-treated cells. Diethylmaleate treatment decreased the harmful ROS in the 7β-OHC-treated or PGC-1α siRNA-transfected cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia, decreased Nrf2 expression and increased CD38 expression in gastrocnemius muscles compared with the WT mice. Diethylmaleate treatment improved the muscle function and decreased the CD38 expression in the old two genotypes. Conclusions: Our study demonstrated that PGC-1α modulated mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2.

ABSTRACT Pathogenic bacteria of the Acinetobacter genus pose a severe threat to human health worldwide due to their strong adaptability, tolerance, and antibiotic resistance. Most isolates of these bacteria harbor a type VI secretion system (T6SS) that allows them to outcompete co-residing microorganisms, but whether this system is involved in acquiring nutrients from preys remains less studied. In this study, we found that Ab25, a clinical isolate of Acinetobacter nosocomialis, utilizes a T6SS to kill taxonomically diverse microorganisms, including bacteria and fungi. The T6SS of Ab25 is constitutively expressed, and among the three predicted effectors, T6e1, a member of the RHS effector family, contributes the most for its antimicrobial activity. T6e1 undergoes self-cleavage, and a short carboxyl fragment with nuclease activity is sufficient to kill target cells via T6SS injection. Interestingly, strain Ab25 encodes an orphan VgrG protein, which when overexpressed blocks the firing of its T6SS. In niches such as dry plastic surfaces, the T6SS promotes prey microorganism-dependent survival of Ab25. These results reveal that A. nosocomialis employs T6SSs that are highly diverse in their regulation and effector composition to gain a competitive advantage in environments with scarce nutrient supply and competing microbes.IMPORTANCEThe type VI secretion system (T6SS) plays an important role in bacterial adaptation to environmental challenges. Members of the Acinetobacter genus, particularly A. baumannii and A. nosocomialis, are notorious for their multidrug resistance and their ability to survive in harsh environments. In contrast to A. baumannii, whose T6SS has been well-studied, few research works have focused on A. nosocomialis. In this study, we found that an A. nosocomialis strain utilizes a contitutively active T6SS to kill diverse microorganisms, including bacteria and fungi. Although T6SS structural proteins of A. nosocomialis are similar to those of A. baumannii, the effector repertoire differs greatly. Interestingly, the T6SS of the A. nosocomialis strain codes for an ophan VgrG protein, which blocks the firing of the system when overexpressed, suggesting the existence of a new regulatory mechanism for the T6SS. Importantly, although the T6SS does not provide an advantage when the bacterium is grown in nutrient-rich medium, it allows A. nosocomialis to survive better in dry surfaces that contain co-existing bacteria. Our results suggest that killing of co-residing microorganisms may increase the effectiveness of strategies designed to reduce the fitness of Acinetobacter bacteria by targeting their T6SS.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, and it has obvious genetic and clinical heterogeneity. Recently, heterozygous ALPK3 truncating variants (ALPK3tv) have been shown to cause HCM. However, the spectrum of ALPK3 variants and their relationships with the clinical characteristics of Chinese patients with HCM remain to be elucidated. Methods and results: Whole-exome sequencing data from 986 patients with HCM and 761 controls without HCM were utilized to analyze ALPK3 variants. Eleven ALPK3tv were detected in 18 patients with HCM (1.8 %), while no such variants were identified in controls. We also detected 21 rare ALPK3 missense variants in 16 patients with HCM (1.6 %) and 8 controls (1.1 %), respectively. ALPK3tv were significantly enriched in patients with HCM (P

Background: Mitochondrial dysregulation in skeletal myocytes is considered a major factor in aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target of rapamycin complex 1 (mTORC1) in aged skeletal muscles. Methods: C2C12 myoblasts were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of DNA damage, mitochondrial membrane potential (Δψm), mitochondrial ROS and PGC-1α protein. The PGC-1α silence in the C2C12 cells was established by siRNA transfection. The levels of DNA damage, Δψm, mitochondrial ROS, Sestrin2 and p-S6K1/S6K1 proteins were observed after the PGC-1α silence in the C2C12 cells. Recombinant Sestrin2 treatment was used to observe the changes of DNA damage, Δψm, mitochondrial ROS and p-S6K1/S6K1 protein in the 7β-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. Wild-type (WT) mice and muscle-specific PGC-1α conditional knockout (MKO) mice, including young and old, were used to analyse the effects of PGC-1α on muscle function and the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles. Recombinant Sestrin2 was administrated to analyse its effects on muscle function in the old WT mice and old MKO mice. Results: 7β-OHC treatment induced DNA damage, mitochondrial dysfunction and decrease of PGC-1α protein in the C2C12 cells. PGC-1α silence also induced DNA damage and mitochondrial dysfunction in the C2C12 cells. Additionally, PGC-1α silence or 7β-OHC treatment decreased the levels of Sestrin2 and p-S6K1/S6K1 protein in the C2C12 cells. Recombinant Sestrin2 treatment significantly improved the DNA damage and mitochondrial dysfunction in the 7β-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia and decreased the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles when compared to the WT mice. Recombinant Sestrin2 treatment improved muscle function and increased p-S6K1 levels in the old two genotypes. Conclusion: This research demonstrates that PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway.

Abstract. Background:. Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. Methods:. This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results:. During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P

[Objective] To address the challenges about renewable energy utilization and significant grid voltage fluctuations in urban rail transit power supply system, a power supply solution based on bidirectional converter technology for traction system is proposed. [Method] The main circuit topology and operational logic of bidirectional converters are introduced. The control characteristics of bidirectional converters under two operating modes of independent power supply and hybrid power supply are presented, and the external characteristic curves combining constant voltage and droop are designed. Using the example of Xuzhou Metro Line 2, tests are conducted for both independent power supply and hybrid power supply under traction and braking conditions for a single train AW0 (unloaded) on the depot test track. Same tests are also performed under normal operation conditions with 12 trains on the mainline. Performance indicators for train operation and bidirectional converters are evaluated. [Result & Conclusion] Bidirectional converters can automatically and smoothly switch between rectification and inversion modes based on the train on-line operation conditions, automatically adapting to the train traction/braking conditions. The use of bidirectional converters in power supply significantly ameliorates train grid voltage fluctuation, preventing working conditions below 1 500 V and enhancing train traction characteristics.

Abstract Background Aslanger’s pattern in electrocardiogram (ECG) indicates that patients may have acute inferior myocardial infarction(AMI) with concomitant critical stenoses on other coronary arteries, which needs to be evaluated the timing of revascularization as risk equivalents of ST elevation myocardial infarction(STEMI). Case Presentation The patient was a 62-year-old male with chief complaint of intermittent exertional subxiphoid pain for 20 days from 30th June. One day after the last episode (19th July), the 18-lead electrocardiogram showed ST segment elevation of 0.05-0.1mV in lead III, ST segment depression in leads I, avL, and V2-V6, T wave inversion with positive terminal vector in lead V4-V5, and positive T wave in lead V6, which indicated Aslanger’s pattern. With increased Troponin I (0.162ng/mL, 0-0.02), The patient was diagnosed as acute non-ST-segment elevation myocardial infarction (NSTEMI) and admitted to coronary ward on 20th July. The coronary angiography showed 95% stenosis in the distal left main coronary artery (LM) to the ostium of the left anterior descending artery (LAD), 90% stenosis in the proximal segment of the LAD, and 80% stenosis in the middle segment of the LAD, and TIMI blood flow was graded score 2. Three drug-eluting stents were implanted at the lesions. The patient’s ECG returned close to normal one month after revascularization. Conclusion We presented an acute coronary syndrome case whose ECG showed with Aslanger’s pattern (i.e., isolated ST-segment elevation in lead III, associated ST-segment depression in lead V4-V6 with positive T wave/terminal vector, and greater ST-segment elevation in lead V1 than in lead V2), and was confirmed severe stenosis of the LM and the proximal segment of the LAD via coronary angiography. In clinical practice, especially in the emergency, patients with ECG presenting Aslanger’s pattern should be urgently evaluated with prompt treatment, and the timing of emergency coronary angiography and revascularization should be evaluated to avoid adverse outcomes caused by delayed treatment.

Abstract The accurate preoperative diagnosis and tracking of lung adenocarcinoma is hindered by non-targeting and diffusion of dyes used for marking tumors. Hence, there is an urgent need to develop a practical nanoprobe for tracing lung adenocarcinoma precisely even treating them noninvasively. Herein, Gold nanoclusters (AuNCs) conjugate with thyroid transcription factor-1 (TTF-1) antibody, then multifunctional nanoprobe Au-TTF-1 is designed and synthesized, which underscores the paramount importance of advancing the machine learning diagnosis and bioimaging-guided treatment of lung adenocarcinoma. Bright fluorescence (FL) and strong CT signal of Au-TTF-1 set the stage for tracking. Furthermore, the high specificity of TTF-1 antibody facilitates selective targeting of lung adenocarcinoma cells as compared to common lung epithelial cells, so machine learning software Lung adenocarcinoma auxiliary detection system was designed, which combined with Au-TTF-1 to assist the intelligent recognition of lung adenocarcinoma jointly. Besides, Au-TTF-1 not only contributes to intuitive and targeted visualization, but also guides the following noninvasive photothermal treatment. The boundaries of tumor are light up by Au-TTF-1 for navigation, it penetrates into tumor and implements noninvasive photothermal treatment, resulting in ablating tumors in vivo locally. Above all, Au-TTF-1 serves as a key platform for target bio-imaging navigation, machine learning diagnosis and synergistic PTT as a single nanoprobe, which demonstrates attractive performance on lung adenocarcinoma. Graphical Abstract

Abstract Background Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ezetimibe and statins, respectively, which are important for the progression of atherosclerosis. However, CAC’s genetic susceptibility with above targets is still unknown. We aimed to investigate the association of NPC1L1 and HMGCR gene polymorphisms with CAC in patients with premature triple-vessel disease (PTVD). Methods Four single nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, rs2073547) of NPC1L1, and three SNPs (rs12916, rs2303151, rs4629571) of HMGCR were genotyped in 872 PTVD patients. According to the coronary angiography results, patients were divided into low-degree CAC group and high-degree CAC group. Results A total of 872 PTVD patients (mean age, 47.71 ± 6.12; male, 72.8%) were finally included for analysis. Multivariate logistic regression analysis showed no significant association between the SNPs of NPC1L1 and HMGCR genes and high-degree CAC in the total population (P > 0.05). Subgroup analysis by gender revealed that the variant genotype (TT/CT) of rs4720470 on NPC1L1 gene was associated with increased risk for high-degree CAC in male patients only (OR = 1.505, 95% CI: 1.008–2.249, P = 0.046) in dominant model, but no significant association was found in female population, other SNPs of NPC1L1 and HMGCR genes (all P > 0.05). Conclusions We reported for the first time that the rs4720470 on NPC1L1 gene was associated with high-degree CAC in male patients with PTVD. In the future, whether therapies related to this target could reduce CAC and cardiovascular events deserves further investigation.

Abstract Background Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). Methods A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. Results An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026–1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. Conclusions The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD. Graphical Abstract

Reinforcement learning (RL) has been shown to be effective in path planning. However, it usually requires exploring a sufficient number of state–action pairs, some of which may be unsafe when deployed in practical obstacle environments. To this end, this paper proposes an end-to-end planning method based model-free RL framework with optimization, which can achieve better learning performance with a safety guarantee. Firstly, for second-order drone systems, a differentiable high-order control barrier function (HOCBF) is introduced to ensure the output of the planning algorithm falls in a safe range. Then, a safety layer based on the HOCBF is proposed, which projects RL actions into a feasible solution set to guarantee safe exploration. Finally, we conducted a simulation for drone obstacle avoidance and validated the proposed method in the simulation environment. The experimental results demonstrate a significant enhancement over the baseline approach. Specifically, the proposed method achieved a substantial reduction in the average cumulative number of collisions per drone during training compared to the baseline. Additionally, in the testing phase, the proposed method realized a 43% improvement in the task success rate relative to the MADDPG.

With the development of the power system, power users begin to use their own power supply in order to improve the power economy, but this also leads to the occurrence of the risk of self-provided power supply. The actual distribution network has few samples of power supply risk and it is difficult to identify the power supply risk by using conventional deep learning methods. In order to achieve high accuracy of self-provided power supply risk identification with small samples, this paper proposes a combination of transfer learning, convolutional block attention module (CBAM), and convolutional neural network (CNN) to identify the risk of self-provided power supply in an active distribution network. Firstly, in order to be able to further identify whether or not a risk will be caused based on completing the identification of the faulty line, we propose that it is necessary to identify whether or not the captive power supply on the faulty line is in operation. Second, in order to achieve high-precision identification and high-efficiency feature extraction, we propose to embed the CBAM into a CNN to form a CBAM-CNN model, so as to achieve high-efficiency feature extraction and high-precision risk identification. Finally, the use of transfer learning is proposed to solve the problem of low risk identification accuracy due to the small number of actual fault samples. Simulation experiments show that compared with other methods, the proposed method has the highest recognition accuracy and the best effect, and the risk recognition accuracy of active distribution network backup power is high in the case of fewer samples.

Shelf seas are experiencing a rise in shallow gas leaks, primarily methane, raising concerns due to their environmental impact. However, the effect of the leaks on early diagenesis remains poorly understood. This study analyzes sediment lithology, organic geochemistry and porewater geochemistry of two short cores collected nearby the pockmarks in the muddy inner shelf of the East China Sea. Our findings clearly demonstrate the impact of methane leakage on early diagenesis, evidenced by the shallower position of the SMTZ (sulfate-methane transition zone), higher concentrations of uranium (U), vanadium (V), and manganese (Mn) in the porewater near and above the SMTZ, and downcore decrease in Mg2+, Ca2+, and Sr2+ concentrations versus increase in Mg2+/Ca2+ and Sr2+/Ca2+ ratios. Their profile variations and the difference between two cores are determined by the intensity of methane leakage. The estimated methane diffusive flux of 619 mmol m-2 yr-1 at YEC7–2 is roughly 8.5 times that at YEC7–1 (73 mmol m-2 yr-1), consistent with a shorter distance of YEC7–2 to the pockmark with active methane leakage. A schematic model is summarized to demonstrate the response of early diagenesis processes to the increasing methane leakages in response to changing sedimentation regimes from accretion to severe erosion. This study undoubtedly improves our understanding mutual promotion effect between seafloor erosion and gas leakage, and their impact on early diagenesis processes and resultant porewater geochemical changes and authigenic mineral records.

Background: Accumulating small unruptured intracranial aneurysms are detected due to the improved quality and higher frequency of cranial imaging, but treatment remains controversial. While surgery or endovascular treatment is effective for small aneurysms with a high risk of rupture, such interventions are unnecessary for aneurysms with a low risk of rupture. Consequently, it is imperative to accurately identify small aneurysms with a low risk of rupture. The purpose of this study was to develop a clinically practical model to predict small aneurysm ruptures based on a radiomics signature and clinical risk factors. Methods: A total of 293 patients having an aneurysm with a diameter of less than 5 mm, including 199 patients (67.9 %) with a ruptured aneurysm and 94 patients (32.1 %) without a ruptured aneurysm, were included in this study. Digital subtraction angiography or surgical treatment was required in all cases. Data on the clinical risk factors and the features on computed tomography angiography images associated with the aneurysm rupture status were collected simultaneously. We developed a clinical–radiomics model to predict aneurysm rupture status using multivariate logistic regression analysis. The combined clinical–radiomics model was constructed by nomogram analysis. The diagnostic performance, clinical utility, and model calibration were evaluated by operating characteristic curve analysis, decision curve analysis, and calibration analysis. Results: A combined clinical–radiomics model (Area Under Curve [AUC], 0.85; 95 % confidence interval [CI], 0.757–0.947) showed effective performance in the operating characteristic curve analysis. In the validation cohort, the performance of the combined model was better than that of the radiomics model (AUC, 0.75; 95 % CI, 0.645–0.865; Delong's test p-value = 0.01) and the clinical model (AUC, 0.74; 95 % CI, 0.625–0.851; Delong's test p-value

Summary: Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

ObjectiveThe present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy.MethodWe performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases.ResultsA total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18–78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P

Understanding the environmental significance of pollen and spores in alluvial plains is important for stratigraphic correlation and paleoenvironmental reconstruction. This paper presents palynological data from the North China Plain and explores their relationship with paleoflood records and human impacts since the Holocene. Our data reveal that pollen concentration and pollen assemblage vary in flood deposits (including overbank deposits and slackwater deposits) and inter-flood deposits (including sandy soils and lacustrine deposits). Flood deposits have higher fern percentages (28.6%) and lower herbaceous percentages (14.8%) compared to inter-flood deposits, though slackwater deposits share similar pollen concentrations and assemblages with sandy soils. Notably, overbank deposits are characterized by pollen-poor zones and aggregation of deteriorated pollen grains, especially in Unit III (755–385 cm, ca. 3.2–2.2 ka) and Unit V (190–0 cm, after ca. 0.6 ka). These findings suggest that overbank deposits correspond to strengthened hydrodynamic conditions at the flood-peak stage. Furthermore, the indicative pollen and spores provide compelling evidence for intensifying human impact in the North China Plain since the late Holocene. An aggregation of Selaginella sinensis at the depth of 640–610 cm indicates deforestation in the uplands since ca. 2.9 ka. Similarly, a sharp increase in Malvaceae percentage at the depth of 285–215 supports historical records of initial cotton planting in the Tang Dynasty (ca. 1.4–1.1 ka). The study underscores the value of palynological analysis for reconstructing paleoenvironment and human-environment interactions, providing a robust framework for understanding landscape evolution in the North China Plain.

This study delves into the multifaceted effects of multi-walled carbon nanotubes (MWCNT) incorporation on phosphogypsum's properties. We investigated the phase composition and morphology of phosphogypsum and observed the influence of MWCNT on the setting time, flexural strength, compressive strength, water resistance, and hydration process. The results demonstrated that MWCNT significantly abbreviates the setting time of phosphogypsum, enhances its absolute dry flexural strength and compressive strength, and improves water resistance, with optimal effects occurring at a MWCNT content of around 1.00%. Nonetheless, these benefits diminish and can even be counterproductive if MWCNT content is excessively high. The enhanced properties of phosphogypsum upon MWCNT addition can be ascribed to the filling effect and mechanical interlocking facilitated by MWCNT. Additionally, MWCNT promoted the hydration of phosphogypsum, as evidenced by calorimetric measurements.

Abstract Objectives Lung cancer is a major public health concern and represents the most common cause of cancer‐related death worldwide. Among eukaryotes, the G protein‐coupled receptor (GPCR) family stands as the largest group of membrane proteins. Alterations in GPCR gene expression and dysregulation of signal transduction have been recognized as the markers of malignancy. As a member of the GPCR family, G protein‐coupled receptor 37 (GPR37) exhibits unknown functions in tumors, particularly in non‐small‐cell lung cancer (NSCLC) Methods We explored the expression and prognosis of GPR37 in NSCLC through TCGA, GTEx, GEO, and GEPIA2. We detected the expression of GPR37 in NSCLC tissues and cell lines. The study explored the influence of GPR37 on tumor cell proliferation. Furthermore, we examined the effects of GPR37 on tumor cell apoptosis and invasion. Most importantly, we investigated whether GPR37 affects cisplatin‐induced drug resistance in NSCLC. Furthermore, by conducting animal experiments, we assessed the impact of GPR37 on NSCLC and delved into underlying mechanisms. Results (1) In NSCLC, the expression of GPR37 is markedly higher than that in corresponding normal tissues. We found that elevated GPR37 expression predicts an unfavorable prognosis. (2) It was demonstrated that GPR37 positively regulates NSCLC cell invasion, migration, and proliferation, suppresses cell apoptosis, heightens resistance to cisplatin, and promotes tumor formation and growth. Conversely, we observed that GPR37 knockdown suppresses NSCLC cell invasion, migration, and proliferation, promotes cell apoptosis, increases sensitivity to cisplatin, and affects tumor formation and growth. (3) GPR37 activates PI3K/Akt/mTOR signal transduction pathways to mediate epithelial‐mesenchymal transition (EMT), thereby promoting the progression of NSCLC. Conclusions It was suggested that GPR37 acts a crucial role in promoting the occurrence and development of NSCLC. Knockdown of GPR37 significantly inhibits the occurrence and development of NSCLC. Therefore, our findings demonstrated that GPR37 may represent a viable therapeutic target for NSCLC.

Background: Left bundle branch pacing (LBBP) is a physiological pacing that captures the main left bundle or its proximal branch. Electromechanical activation time (EMAT) is an acoustic cardiographic metric that provides a simple method for evaluating left ventricular (LV) synchrony. Prolonged EMAT reflects impaired LV electromechanical coupling. Objective: The purpose of this study was to explore whether EMAT can confirm that LBBP produces more satisfactory LV electromechanical synchronization than conventional right ventricular pacing modalities. Methods: Patients with standard pacing indications and narrow QRS duration were recruited for this study. Unipolar pacing under 3 different modalities—right ventricular apical pacing (RVAP), right ventricular high septal pacing (RVHSP), and LBBP—were successively performed in each patient. Pacing parameters, echocardiographic characteristics, and acoustic cardiographic parameters at different pacing modalities and during normal rhythm were collected. Results: A total of 55 patients were enrolled, and all had successful LBBP. Left ventricular activation time (LVAT) was significantly associated with EMAT, with LVAT vs EMAT correlation coefficient of 0.665 (P

Abstract Background The factors associated with postoperative hypokalemia in patients with oral cancer remain unclear. We determined the preoperative factors associated with postoperative hypokalemia in patients with oral cancer following en bloc cancer resection and established a nomogram for postoperative hypokalemia prediction. Methods Data from 381 patients with oral cancer who underwent en bloc cancer resection were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the risk factors for postoperative hypokalemia. We used receiver operating characteristic (ROC) curves to quantify the factors’ effectiveness. A nomogram was created to show each predictor’s relative weight and the likelihood of postoperative hypokalemia development. The multinomial regression model’s effectiveness was also evaluated. Results Preoperative factors, including sex, preoperative serum potassium level, and preoperative platelet-to-lymphocyte ratio (PLR), were significantly associated with postoperative hypokalemia. Based on the ROC curve, the preoperative serum potassium and PLR cut-off levels were 3.98 mmol/L and 117, respectively. Further multivariate analysis indicated that female sex, preoperative serum potassium level

Abstract Background Quantitative proteomics is an indispensable tool in life science research. However, there is a lack of reference materials for evaluating the reproducibility of label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based measurements among different instruments and laboratories. Results Here, we develop the Quartet standard as a proteome reference material with built-in truths, and distribute the same aliquots to 15 laboratories with nine conventional LC–MS/MS platforms across six cities in China. Relative abundance of over 12,000 proteins on 816 mass spectrometry files are obtained and compared for reproducibility among the instruments and laboratories to ultimately generate proteomics benchmark datasets. There is a wide dynamic range of proteomes spanning about 7 orders of magnitude, and the injection order has marked effects on quantitative instead of qualitative characteristics. Conclusion Overall, the Quartet offers valuable standard materials and data resources for improving the quality control of proteomic analyses as well as the reproducibility and reliability of research findings.

Abstract Clonal hematopoiesis (CH)—age-related expansion of mutated hematopoietic clones—can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises questions as to their origin, selection, and impact. We integrate sequence and genotype array data in up to 482,378 UK Biobank participants to demonstrate shared genetic architecture across CH types. Our analysis suggests a cellular evolutionary trade-off between different types of CH, with LOY occurring at lower rates in individuals carrying mutations in established CHIP genes. We observed co-occurrence of CHIP and mCAs with overlap at TET2, DNMT3A, and JAK2, in which CHIP precedes mCA acquisition. Furthermore, individuals carrying overlapping CH had high risk of future lymphoid and myeloid malignancies. Finally, we leverage shared genetic architecture of CH traits to identify 15 novel loci associated with leukemia risk.

Abstract Background Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method. Methods Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots. Results A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall’s coefficient of concordance of indicators at all levels was 0.564–0.594 (p

As an important interface between unmanned aerial vehicles (UAVs) and ships, the stability and motion control compensation technology of the shipborne UAV landing platform are paramount for successful UAV landings. This paper has designed a new control compensation method for an autonomous UAV landing platform to address the impact of complex sea conditions on the stability of UAV landing platforms. Firstly, the parallel Stewart platform was introduced as the landing platform, and its structure was analyzed with forward and inverse kinematic calculations conducted in Matlab to verify its accuracy. Secondly, a least-squares recursive AR prediction algorithm was designed to predict the future attitudes of ships under varying sea conditions. Finally, the prediction algorithm was combined with the platform’s control strategy and a dual-sensor system was adopted to ensure the stability of the UAV landing process. The experimental results demonstrate that these innovative improvements enhanced the compensation accuracy by 59.6%, 60.3%, 48.4%, and 47.9% for the rolling angles of 5° and 10° and the pitching angles of 5° and 10°, respectively. Additionally, the compensation accuracy for the roll and pitch in sea states 2 and 5 improved by 51.2%, 59.4%, 58.7%, and 55.9%, respectively, providing technical support for UAV missions such as maritime rescue and exploration.

Non-invasive load monitoring (NILM) deduces changes in energy consumption patterns and operational statuses of electrical equipment from power signals in the feed line. With the emergence of fine-grained power load distribution, the importance of utilizing this technology for implementing demand-side energy management in smart grid development has become increasingly prominent. To address the issue of low load identification accuracy stemming from complex and diverse load types, this paper introduces a NILM method based on uniform manifold approximation and projection (UMAP) reduction and enhanced density-based spatial clustering of applications with noise (DBSCAN). Firstly, this paper combines the characteristics of user load under transient and steady-state conditions and selects data with significant differences to construct a load-characteristic database. Additionally, UMAP is employed to reduce the dimensionality of high-dimensional load features and rebuild a load feature database. Subsequently, DBSCAN is utilized to categorize typical user loads, followed by a correlation analysis with the load-characteristic database to determine the types or classes of loads that involve switching actions. Finally, this paper simulates and analyzes the proposed method using the electricity consumption data of industrial users from the CER–Electricity–Data dataset. It identifies the electricity load data commonly utilized by users in a specific area of Zhejiang Province in China. The experimental results indicate that the accuracy of the proposed non-invasive load identification method reaches 95%. Compared to the wavelet transform, decision tree, and backpropagation network methods, the improvement is approximately 5%.

A single-frequency, Q-switched Er:YAG laser, pumped by a 1532 nm fiber laser, has been demonstrated. At the pulse repetition frequency (PRF) of 200 Hz, the maximum single-frequency laser of 5.5 mJ is attained, and, correspondingly, the pulse width is 212 ns. Using the heterodyne technique, the single-frequency laser spectrum’s full width at half maximum is determined to be 2.73 MHz. The experimental results show that the single-frequency laser has excellent beam quality factors (M2) of 1.18 and 1.21.

Organic fluorides are widely used in pharmaceuticals, agrochemicals, material sciences, and other fields due to the special physical and chemical properties of fluorine atoms. The synthesis of alkyl fluorinated compounds bearing multiple contiguous stereogenic centers is the most challenging research area in synthetic chemistry and has received extensive attention from chemists. This review summarized the important research progress in the field over the past decade, including asymmetric electrophilic fluorination and the asymmetric elaboration of fluorinated substrates (such as allylic alkylation reactions, hydrofunctionalization reactions, Mannich addition reactions, Michael addition reactions, aldol addition reactions, and miscellaneous reactions), with an emphasis on synthetic methodologies, substrate scopes, and reaction mechanisms.

With off-axis reflection systems with specific distortion values serving as objectives or collimators, it is possible to compensate and correct for spectral line bending in spectroscopic instruments. However, there is limited research on the precise control of distortion, which poses particular challenges in large field-of-view optical systems. This paper presents a method for controlling distortion in off-axis reflection systems. Based on Seidel aberration theory and the relationship between distortion wavefront error and primary ray error, we construct objective functions with structural constraints and aberration constraints. The initial structure with specific distortion values is then solved using a differential evolution algorithm. The effectiveness and reliability of this method are verified through the design of an off-axis three-reflection system. The method provided in this study facilitates the design of remote sensing instruments.