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Mixed-grains magnesium alloy plates with soft-hard-soft layered structure, fabricated by corrugated plate rolling, exhibit simultaneous improvements in both strength and ductility. The corrugated and flat sides primarily consist of twins, necklace grains and recrystallized grains, while the middle layer is dominated by coarse grains with a small amount of twins and necklace grains. As the average strain rate increases, the twin density and shear band decrease. At a constant average strain rate, from the valley-to-peak, the twin density and the number of coarse grains gradually decrease, while the recrystallization fraction gradually increases. At an average strain rate of 4.3 s−1, the corrugated rolled plates with R = 3 mm achieve an optimal balance of strength (262.6 MPa) and ductility (30.6 %). The corrugated side and flat side contribute to strength through fine grain strengthening and orientation strengthening, while the middle layer with coarse grains provides plasticity. The ordered orientation gradient “sandwich” texture further ensuring ductility. The hard-soft-hard layered structure and the configuration of coarse grains surrounded by fine grains synergistically lead to exceptional mechanical properties.

This study presents an in-depth analysis on the microstructural evolution of the low-activation Ti8VCrMnFeCu2 alloy under helium irradiation. The irradiation-induced vacancies and the change of Cu nanoprecipitates were characterized using slow positron-beam Doppler broadening spectroscopy (DBS) and transmission electron microscopy (TEM). It is revealed that the effective open volume of defects induced by helium irradiation was inhibited at room temperature even at a relatively high dose (3 × 101⁷ ions/cm2, ∼10.5 dpa). This is attributed to the formation of HemVn, which effectively decreases migration and aggregation of vacancies. Moreover, TEM results clearly illustrate the enhanced swelling resistance exhibited in the alloy. The estimated swelling rate is ∼0.092%/dpa with 1 × 101⁷ ions/cm2 at 723 K. This study demonstrates that Cu nanoprecipitates can effectively serve as traps for helium bubbles, as they capture helium atoms and inhibit their diffusion.

Abstract Background The standard treatment for elderly patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy with S-1. However, the 3-year overall survival (OS) is limited to approximately 40%. Tislelizumab is the first- and second-line standard treatment for advanced ESCC with tolerable toxicity. In this study, we aimed to explore a new curative strategy for locally advanced unresectable ESCC in the elderly by combining tislelizumab with chemoradiotherapy. Methods This study is an open-label, multicenter, investigator-initiated phase II clinical trial in older patients with inoperable locally advanced ESCC evaluating tislelizumab plus concurrent chemoradiotherapy compared with concurrent chemoradiotherapy. The main inclusion criteria were pathological confirmation of locally advanced inoperable ESCC at clinical cT1N2-3M0 or cT2-4bN0-3M0 (stage II–IVA), age ≥ 70 years, absence of previous systemic anti-tumor therapy, and adequate organ function. A total of 136 patients will be recruited from approximately seven centers (in Tianjin, Chengdu, Taiyuan, Zhengzhou, Shijiazhuang, Changsha, Nanjing) over a period of 18 months and randomized in a 1:1 ratio to receive tislelizumab in combination with concurrent chemoradiotherapy (tislelizumab + S-1 + radiotherapy) or concurrent chemoradiotherapy (S-1 + radiotherapy). The efficacy and safety of the treatment will be evaluated during the therapy and follow-up period until disease progression, death, or the end of the trial. The primary study endpoint was investigator-assessed progression-free survival (PFS), and secondary study endpoints were OS, objective response rate (ORR), duration of remission (DOR), and safety. Fresh or archival tumor tissues and peripheral blood samples will be used in exploratory studies. Discussion This study is the first “programmed death-1 (PD-1) inhibitor combined with concurrent chemoradiotherapy” for elderly patients with inoperable locally advanced ESCC (NCT06061146). The synergistic efficacy of combined definitive concurrent chemoradiotherapy with tislelizumab is expected to result in survival benefits for elderly patients with inoperable locally advanced ESCC. Because S-1 plus concurrent radiotherapy is the standard treatment option for locally advanced ESCC in older patients, the combination of definitive concurrent chemoradiotherapy and tislelizumab has the potential to change the standard ESCC therapeutic strategy with comparable safety. Trial registration ClinicalTrials.gov NCT06061146.Registered 9/10/2023.

The tension leg platform is a typical compliant platform that is connected to the seabed through tension leg tendons. However, it is hard to characterize tension leg tendons due to the complexity of their force and motions as well as the lack of full-scale test methods. We performed a finite element analysis and full-scale four-point bending fatigue tests on tension leg tendons and connectors to study the fatigue properties of the tension leg tendons (made using 36in-X70 steel pipes) used in the Gulf of Mexico. The maximum deflection and the maximum stress of samples under complex loading were estimated through finite element simulation to ensure the testing requirements, including load intensity, load method, load path, and frequency. The maximum equivalent strain and the corresponding position were then determined through testing, which were further compared with simulation results to verify their accuracy and applicability. The maximum strain amplitude from simulations was 761.42 με, while the equivalent strain amplitude obtained through tests was 734.90 με, which is close to the simulation result. In addition, when the number of fatigue cycles reached 1.055 million, sample damage did not occur. It confirms that the fatigue performance of the tendon steel pipe weld is better than the C1 curve value shown in the DNV RP C203 specification. The proposed full-scale approach to study the fatigue properties of tension leg tendons can provide a reference for domestic engineering design and manufacture of tension leg tendons as well as promote the localization of test equipment.

Abstract The secondary prevention strategy for cardiovascular disease (CVD) does not include anti-inflammatory treatment, which may lead to long-term inflammation in some patients. The aim of this study was to assess the association between inflammatory risk based on the Glasgow Prognostic Score (GPS) and long-term mortality risk in patients with CVD. This study included 3833 patients (≥ 20 years old) with CVD in the National Health and Nutrition Survey from 1999 to 2010 in the United States. The mortality rate was determined by correlation with the National Death Index on December 31, 2019. The GPS consists of the serum C-reactive protein and the serum albumin. The primary outcome was all-cause death, which included cardiac death and non-cardiac death. Cox proportional hazards adjusted for demographic factors and traditional cardiovascular risk factors were used to test the impact of the GPS on mortality. The sensitivity analysis was conducted on subsets within the cohort of patients with CVD, including congestive heart failure, coronary artery disease, angina, heart attack, and stroke. Among 3833 CVD patients with a median follow-up of 9.6 years, 2431 (63.4%) all-cause deaths, 822 (21.4%) cardiac deaths, and 1609 (41.9%) non-cardiac deaths were recorded. After full model adjustment, compared with those of the GPS (0) group, the hazard ratios (HRs) of all-cause death for GPS (1) and GPS (2) were 1.66 (95% confidence interval (CI), 1.48–1.86) and 2.75 (95% CI 2.01–3.75), respectively (P for trend

Abstract Background Hypothyroidism, a prevalent thyroid hormone abnormality identified by biochemical indicators, is prone to serious consequences because of its insidious clinical manifestations and easy underdiagnosis. This research aimed to elucidate the relationships between indicators of lipid and glucose metabolism and hypothyroidism and to assess the value of metabolic indicators for hypothyroidism. Methods Prevalence surveys were conducted utilizing information from 3254 NHANES individuals who passed screening between 2007 and 2012. Comparisons of baseline characteristics, assessment of logistic regression and subgroup analyses, visualization of restricted cubic splines curves, and validation of causal mediation analyses were performed to obtain a comprehensive view of the relationships between indicators of lipid and glucose metabolism and hypothyroidism. Results Lipid and glucose metabolism indicators, especially the unconventional parameters triglyceride‒glucose index (TyG) and remnant cholesterol (RC) and the conventional parameter triglyceride (TG), exhibited robust positive relationships with hypothyroidism and served as crucial mediators in the pathways by which hypothyroidism affects health outcomes. Indicators were varying suggestive for hypothyroidism in distinct populations, with TyG being relatively more valuable. Conclusions Indicators of lipid and glucose metabolism (TyG, TG, and RC) were intimately associated with hypothyroidism, with potential applications in the assessment and management of hypothyroidism.

Abstract Despite the outstanding clinical success of immunotherapy, its therapeutic efficacy in glioblastoma (GBM) is still limited. To identify critical regulators of GBM immunity, we constructed a mouse single-guide RNA (sgRNA) library corresponding to all disease-related immune genes, and performed an in vivo CRISPR knockout (KO) screen in syngeneic GBM mouse models. We demonstrated that the deletion of GDF15 in GBM cells ameliorated the immunosuppressive tumor microenvironment (TME) and enhanced the antitumor efficacy of immune checkpoint blockade (ICB) response. Moreover, we designed unique nanoparticles for efficient encapsulation of CRISPR-Cas9, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for GDF15 gene therapy. The CRISPR-Cas9 nanoparticles, known as ANPSS (Cas9/sgRNA), are easily created by enclosing a single Cas9/sgRNA complex in a polymer shell that is sensitive to glutathione. This shell also contains a dual-action ligand that aids in crossing the blood‒brain barrier, targeting tumor cells, and selectively releasing Cas9/sgRNA. Our encapsulating nanoparticles demonstrated promising GBM targeting, resulting in high GDF15 gene editing efficiency within brain tumors while showing minimal off-target gene editing in high-risk tissues. Treatment with ANPSS (Cas9/sgGDF15) effectively halted tumor growth, reversed immune suppression, and enhanced the efficacy of ICB therapy. These results emphasize the potential role of GDF15 in modulating the immune microenvironment and enhancing the effectiveness of current immunotherapy strategies for GBM. Graphical Abstract

Abstract Background Patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) face high mortality rates. Extracorporeal Membrane Oxygenation (ECMO) therapy offers critical support in these cases, yet identifying factors that influence patient outcomes is crucial for improving survival rates. Methods This retrospective study included 63 patients with AMI and CS who underwent ECMO therapy at our institution from January 2020 to December 2023. Patients were categorized into survivors (n = 33) and non-survivors (n = 30) based on 30-day outcomes. Data collected included demographics, clinical history, hemodynamic and biomarker parameters, and treatment details such as time from symptom onset to percutaneous coronary intervention (PCI) and the use of intra-aortic balloon pump (IABP). Logistic regression models and ROC curve analysis were used to evaluate the predictive value of various factors. Results Non-survivors had significantly higher arterial blood lactate levels (8.0 [6.2, 11.0] mmol/L vs. 4.8 [3.0, 8.5] mmol/L, p = 0.015) and required more intensive vasoactive support, as indicated by higher Vasoactive-Inotropic Scores (VIS) (130 [IQR: 105, 175] vs. 100 [IQR: 60, 115], p = 0.016). They also experienced longer delays from symptom onset to PCI (15.5 [IQR: 11.0, 20.5] hours vs. 9.5 [IQR: 7.0, 12.0] hours, p = 0.001). The prevalence of left main coronary artery disease (33.3% vs. 12.1%, p = 0.013) and triple vessel disease (36.7% vs. 9.1%, p = 0.002) was higher in non-survivors. ROC analysis identified arterial blood lactate (AUC = 0.6909), time from onset to PCI (AUC = 0.7667), and VIS (AUC = 0.703) as significant predictors of prognosis. Logistic regression showed that arterial blood lactate (OR = 1.884, p = 0.039), VIS (OR = 1.122, p = 0.033), and time from onset to PCI (OR = 108.271, p = 0.039) were significantly associated with worse outcomes. Conclusions Elevated arterial blood lactate, prolonged time to PCI, and higher VIS could be important predictors of poor outcomes in AMI-CS patients undergoing ECMO therapy. Timely intervention, including rapid revascularization and effective management of metabolic disturbances, might be key to improving survival.

Abstract Avian influenza viruses (AIVs) present an ongoing threat of human infections. Continuous surveillance is important for detecting new infections and verifying prevention and control measures. Swabs of the external environment and throat swabs of employees were collected from six farmers’ markets in Beijing to detect influenza A virus. Positive samples were sequenced, and their genetic characteristics analyzed. In total, 3251 environmental samples were collected from 2019 to 2023, 11 of which were positive for influenza A virus (positivity rate of 0.34%), including nine for H9N2 and two for H7N9. In a genetic analysis, all H7N9 samples showed low pathogenicity, and no mutations at highly pathogenic sites were detected. All 1135 throat swab samples from staff were negative for influenza A virus. At present, the detection rate of AIVs in farmers’ markets is very low, and no adaptive mutations allowing cross-host transmission were found, indicating a low risk of AIV infection among the people of Beijing.

To recover coal resources as much as possible, the working face of small coal pillars has been gradually increased. However, the small coal pillar will cause the compression and air leakage, which may have an adverse effect on the fire prevention of the working face. This study takes 131103 working face of Liuzhuang Coal Mine as the research object, and studies the influence of small and medium-sized coal pillars on the goaf of the adjacent 131101 working face. The temperature and gas volume fraction of adjacent goaf are monitored by four small coal pillar holes combined with closed wall observation holes. Through the method of releasing SF6 tracer gas through the reserved pipeline in the return air tunnel, the air leakage characteristics of small coalpillar to adjacent goaf are studied. The results show that the large-range compression time of small coal pillar is mainly in the roof periodic weighting period, the key area of air leakage is 20 m miles behind the support; the advance influence range of air leakage of small coal pillar is about 135 m, and this part of coal can effectively prevent coal spontaneous combustion by installing temperature sensors or gas monitoring in advance.

Abstract Background The triglyceride-glucose (TyG) index is recognized as an alternative measure of insulin resistance (IR) and has been linked to the risks of cardiovascular disease (CVD) and mortality. This study aimed to evaluate whether the association between the TyG index and CVD mortality is influenced by the use of antidiabetic and hypolipidemic agents, given their potential modifying effects on the TyG index. Methods Participants from the National Health and Nutrition Examination Survey (1999–2018) were included in the study. Mortality outcomes were tracked through linkage with National Death Index records until December 31, 2019. Data on the use of antidiabetic and hypolipidemic medications (including prescribed insulin, diabetic pills, and cholesterol-lowering agents) were self-reported by participants. Results A total of 5,046 adults (representing 42,753,806 individuals, weighted mean age 61.08 years [SE: 0.24]; 49.35% female) were analyzed. The TyG index was significantly associated with all-cause and CVD mortality, and these associations were modified by the use of antidiabetic and hypolipidemic agents (p

Abstract Glioblastoma (GBM) is a primary brain tumor known for its high levels of aggressiveness and resistance to current treatments such as radiotherapy and chemotherapy. As a result, there is a pressing need for innovative therapeutic approaches to combat GBM. Thus, we have developed an engineered multifunctional extracellular vesicle (EV) delivery system that offers an "all-in-one" strategy for GBM therapy. Our approach involved the use of genetic engineering to the long-lasting production of PD-1 and the brain-specific peptide angiopep-2 on the surface of EVs. These modified EVs were then utilized to rejuvenate exhausted CD8+ T cells blocking PD-L1, resulting in significant therapeutic benefits for GBM treatment. Furthermore, the EVs contained Cas9 protein and sgRNA for precise and minimally invasive gene therapy, which addressing the key barriers associated with in vivo CRISPR‒Cas9 gene editing treatment. The multigene editing of EVs resulted in efficient intratumor multisite gene editing (PLK1: 58.6%, VEGF: 52.7%), leading to the successful apoptosis of tumor cells in vivo and demonstrating an antiangiogenic effect. This research introduces a promising universal platform for combining immune checkpoint blockade therapy with gene editing treatment. Graphical Abstract

Urbanization has increased the surface urban heat island (SUHI) effect. This study uses local climate zones (LCZ) and urban built environment characteristics (UBECs) to explore the factors influencing land surface temperature (LST) and SUHI in various UBECs in Shenyang, China. Google Earth Engine was used to calculate LST. An LCZ map of Shenyang was created to analyze seasonal differences in the SUHI. A correlation model was used to screen the UBEC, and a geographically and temporally weighted regression (GTWR) model was used to explain the spatial variations in the urban heat environment caused by built environments in different seasons. Compared to traditional methods, the GTWR model exhibits better goodness of fit and is more effective in capturing the spatiotemporal heterogeneity of variables. Compact and high-rise areas had higher SUHI effects compared to other LCZs, whereas land-cover LCZs had a cool-island effect. The GTWR model helps planners identify the climatic impacts of each factor in different spatial locations within the study area, as well as variations across seasons. Vegetation-related factors had less impact in densely-built areas, whereas the proportion of blue areas was more effective in alleviating extreme climates in high-density zones. The impact of building density on the heat island effect exhibited substantial spatiotemporal variation, particularly in compact, high-rise LCZs during both seasons. To address extreme winter–summer weather in cold regions, this study examined seasonal SUHIs and their interaction with UBECs, offering strategies and guidance for heat mitigation in urban design.

Objective and Methods This study introduces the adjustments for coalbed methane (CBM) production in the Yanchuannan CBM field‒the first deep CBM field in China. Deep CBM production in this CBM field faces challenges including strong heterogeneity of reservoirs, single arrangement mode of production well patterns, low applicability of conventional hydraulic fracturing, excessively long conventional production cycles, and a high proportion of inefficient wells. To address these challenges, a production capacity construction model for efficient deep CBM production of the field was developed through in-depth geology-engineering integration. Results and ConclusionsThe results indicate that the production capacity construction process of the Yanchuannan CBM field has undergone three stages: large-scale production capacity construction, addressing technological challenges, and technological innovations and their popularization. [Results and Conclusions] The following achievements were obtained: (1) The geological understanding of four critical indicators for the selection of optimal geological-engineering “sweet spots” and efficient CBM production. (2) The concept of fracturing through effective propping and key supporting technologies for reservoir stimulation. (3) The optimal and fast production technologies characterized by four stages, three pressures, and three aspects of control. Based on these achievements, the average cycle for acquiring gas shows was shortened from 240 d to 30 d, and the single-well production was significantly enhanced, with the daily gas production of directional and horizontal wells reaching 2.0×104 m3 and 6.5×104 m3, respectively. The deep CBM reservoirs in the Yanchuannan CBM field exhibit strong heterogeneity, causing difficulties with effective production. Given this, the work philosophy that consolidates overall deployment, implementation in batches, integrated assessment and construction, and rolling production capacity construction was developed for production capacity construction. Adhering to this work philosophy, the production capacity construction was performed through continuous assessment and adjustment of geological-engineering sweet spots and timely optimization of production schemes to effectively avoid the co-occurrence of a substantial number of inefficient wells. This increased the fulfillment rate of production capacity from the initial 84% to 100%, suggesting significantly enhanced economic effects. Based on the concept of geology-engineering integration and the full life cycle of gas reservoir development that consists of well emplacement, well drilling and completion, reservoir stimulation, well tests and production, and gathering, transportation, and processing, the following outcomes were obtained: (1) Rational well spacing that matches reserves, well patterns, and fracture networks, increasing single-well producing reserves by 30% to 50%. (2) The optimal well drilling and completion technology focusing on speed increase and cost reduction, improving the drilling speed by 34%. (3) The low-pressure gathering and transportation technology involving high- and low-pressure gathering and transportation, three-stage pressurization, and inter-station connection, reducing the platform investment by 10.8% and the land use by 20%. The geology-engineering integration practices in the Yanchuannan CBM field provide technical support for the deep CBM industry, holding great demonstration and promotion significance.

Abstract Precisely managing electron transfer pathways throughout the catalytic reaction is paramount for bolstering both the efficacy and endurance of catalysts, offering a pivotal solution to addressing concerns surrounding host structure destabilization and cycling life degradation. This paper describes the integration of B-Ni dual single-atoms within MnO2 channels to serve as an electronic reservoir to direct the electron transfer route during methane catalytic combustion. Comprehensive analysis discovers that B atoms weaken the interaction between O and Mn atoms by forming bonds with lattice oxygen atoms. Meanwhile, Ni atoms facilitate electron transfer to achieve the heightened activity of MnO2. The B-Ni dual-sites instead of Mn (IV) could accommodate excess electrons generated during the reaction to inhibit the formation of high spin Mn (III) species, thereby hindering the Jahn-Teller distortion and maintaining the catalyst stability. This work demonstrates an effective modification strategy to substantially prolong the service life of MnO2-based materials.

Abstract Echinacoside (ECH), one of the most representative phenylethanoid glycosides (PhGs), has considerable neuroprotective effects and is an effective ingredient in numerous commercial drugs. Here, we elucidate the complete ECH biosynthetic pathway in the medicinal plant Cistanche tubulosa. In total, 14 related genes are cloned and functionally characterized. Two upstream pathways for tyrosol biosynthesis from L-tyrosine are identified: one includes separate decarboxylation, deamination and reduction steps; the other uses microbial-like transamination, decarboxylation and reduction steps. In addition, a distinct downstream assembly process from tyrosol to ECH is revealed that includes sequential glucosylation, acylation, hydroxylation, and rhamnosylation to form acteoside, and ends with a final glucosylation converting acteoside to ECH. Furthermore, the de novo synthesis of 23 PhG derivatives is achieved via the heterologous expression of different combinations of the functional genes in tobacco. Our findings provide insights into the biosynthesis of ECH and a platform for alternative production of complex PhGs.

Friction is a considerable boundary condition in aluminum alloy hot extrusion. In this study, ball-on-disc friction tests at temperatures of 25–500 °C were performed to equivalently simulate the interface tribological behaviors between Al–Mg–Si–Cu alloy and die steel in hot extrusion. The wear tracks and wear debris on disc samples were observed by means of ultradepth 3D microscopy, field-emission scanning microscope and energy dispersive spectroscopy. The change trends of wear depth, width and wear rate of aluminium disc with temperature and wear cycles were investigated. The evolutions of wear mechanism and friction coefficient with temperature were revealed. A mechanical analytical model for identifying adhesion and ploughing friction components during friction was established. The results show that as temperature rises, wear rate of aluminum disc increases gradually, while the average friction coefficient increases first rapidly and then decreases, which is associated with the changes of friction and wear mechanisms. The adhesion friction force constitutes the majority of total friction force, while ploughing friction force accounts for less than 3 %. Compared with the large variation of adhesion friction coefficient during friction, shear friction stress can tend to be stable and is not affected by the change of contact area, which may can better characterize the adhesion frictional behavior of die interface in aluminum alloy hot extrusion. The quantitative relationship between temperature and steady shear friction stress was described by an inverse polynomial peak function.

Electromyography (EMG) based Human-Computer Interaction (HCI) through wearable devices frequently encounter variability in body postures, which can modify the amplitude and frequency features of surface EMG (sEMG) signals. This variability often results in reduced gesture recognition accuracy. To enhance the robustness of sEMG-based gesture interfaces, mitigating the effects of body position variability is essential. In this paper, we proposed a Dynamic Balanced Single-Source Domain Generalization (DBSS-DG) transfer learning framework, which only used sEMG signal data from one posture as source domain for model training but can also generate good performance under different body postures as target domain. Validation was performed on the sEMG dataset from 16 subjects across four postures: standing, sitting, walking, and lying. With standing as the source domain, the model achieved gesture recognition accuracies of 90.79 ± 0.09%, 88.78 ± 0.06%, and 90.87 ± 0.1% for sitting, walking, and lying as the target domains, respectively, producing an average improvement of 4.71% over non-transfer learning approaches. Furthermore, the performance of our model exceeded that of many well-known single-source domain generalization methods, establishing its effectiveness in practical applications.

Abstract Background Central obesity and breast cancer (BC) have been identified as relevant by empirical research. The weight-adjusted-waist index (WWI) is a novel methodology for quantifying central obesity. Inspection of the association between WWI and BC in American adult women was the primary goal of the current investigation. Methods Cross-sectional assessments were conducted on information gathered from 10,193 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2018. The waist circumference was divided by the square root of the body’s mass to compute WWI. Data were assessed via descriptive statistics to present data distributions according to BC grouping and WWI grouping, receiver operating characteristic curves (ROCs) to evaluate the obesity indicators’ applied value, logistic regression to reflect associations between WWI and BC prevalence, and restricted cubic splines (RCSs) and subgroup analysis forest plots to visualise and complement the relationships. Results This study enrolled 10,193 participants whose WWI ranged from 8.38 to 14.41, 259 of whom were diagnosed with BC, and the results revealed significant differences in baseline characteristics between the groups. With an area under the curve (AUC) value (95% confidence interval) (CI)of 0.611 (0.577–0.644), WWI was a promising indicator of BC with good application value rather than waist circumference (WC), body mass index (BMI), or waist-height ratio (WHtR). WWI and BC laid out a substantial relationship, yielding an odds ratio (OR) of 1.54 and a 95% CI of (1.34, 1.79), which remained at 1.19 (1.00, 1.42) after considerable adjustments were made, according to the logistic regression analysis. Compared with the lowest quartile of WWI, the highest quartile had a 62% greater in the probability of suffering from BC. With the RCS’s inverted U-shape highlighting the importance of considering the nonlinear nature of the relationship and subgroup analyses reflecting variations among populations, all the results demonstrated that WWI was a well-suggestive indicator of BC hazard. Conclusion The current investigation revealed a meaningful association between the prevalence of BC and WWI, which was superior to other obesity indicators, albeit one that was more complex than the positive relationship initially derived. There existed a turning point for BC prevalence at WWI of approximately 12 cm/√kg. Nevertheless, maintaining WWI in the lower range is critical for preventing and administering BC and minimizing disease risk.

Abstract For surface electromyography (sEMG) based human–machine interaction systems, accurately recognizing the users’ gesture intent is crucial. However, due to the existence of subject-specific components in sEMG signals, subject-specific models may deteriorate when applied to new users. In this study, we hypothesize that in addition to subject-specific components, sEMG signals also contain pattern-specific components, which is independent of individuals and solely related to gesture patterns. Based on this hypothesis, we disentangled these two components from sEMG signals with an auto-encoder and applied the pattern-specific components to establish a general gesture recognition model in cross-subject scenarios. Furthermore, we compared the characteristics of the pattern-specific information contained in three categories of EMG measures: signal waveform, time-domain features, and frequency-domain features. Our hypothesis was validated on an open source database. Ultimately, the combination of time- and frequency-domain features achieved the best performance in gesture classification tasks, with a maximum accuracy of 84.3%. For individual feature, frequency-domain features performed the best and were proved most suitable for separating the two components. Additionally, we intuitively visualized the heatmaps of pattern-specific components based on the topological position of electrode arrays and explored their physiological interpretability by examining the correspondence between the heatmaps and muscle activation areas.

Abstract Aims The prognostic significance of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) in heart failure with preserved ejection fraction (HFpEF) has been well established. HFpEF and atrial fibrillation (AF) commonly coexist, and each contributes to poor outcomes independently. Nevertheless, the ability of NT‐proBNP to predict AF in HFpEF patients remains uncertain. Methods and results A total of 367 HFpEF patients without baseline AF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included. The Cox proportional hazard model was used to assess the association of NT‐proBNP with the risk of AF. The C‐statistic, categorical net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the ability of NT‐proBNP in new‐onset AF prediction. During a median follow‐up of 2.91 years, 17 (4.63%) new‐onset AF cases occurred. Every 1000 pg/mL increase in NT‐proBNP was associated with a 16% increase in the risk of AF occurrence after adjustments (hazard ratio, 1.16 [95% CI, 1.02–1.32]). NT‐proBNP showed a moderate performance for new‐onset AF at 3 years (C‐statistic, 0.67). Adding NT‐proBNP to CHADS2/R2CHADS2/CHA2DS2‐VASc/C2HSET scores improved their predictive performance for AF risk (CHADS2: C‐statistic, 0.63, CHADS2+NT: C‐statistic, 0.69, NRI, 47.46%, IDI, 1.18%; R2CHADS2: C‐statistic, 0.65, R2CHADS2+NT: C‐statistic, 0.70, NRI, 48.03%, IDI, 0.51%; CHA2DS2‐VASc: C‐statistic, 0.67, CHA2DS2‐VASc+NT: C‐statistic, 0.72, NRI, 49.41%, IDI, 0.86%; C2HSET: C‐statistic, 0.77, C2HSET+NT: C‐statistic, 0.80, NRI, 50.32%, IDI, 1.58%). Conclusions Among patients with HFpEF, the NT‐proBNP level was positively associated with the incidence of new‐onset AF and may be a promising predictor.

Fibrodysplasia ossificans progressiva and progressive osseous heteroplasia are genetic forms of heterotopic ossification (HO). Fibrodysplasia ossificans progressiva is caused by ACVR1 gene mutations, while progressive osseous heteroplasia is caused by GNAS gene mutations. Nongenetic HO typically occurs after trauma or surgery, with an occurrence rate of 20–60%. It can also be observed in conditions such as diffuse idiopathic skeletal hyperostosis, spinal ligament ossification, ankylosing spondylitis, and skeletal fluorosis. The exact cause of nongenetic HO is not entirely clear. More than 100 types of miRNAs have been identified as being linked to the development of HO. Some miRNAs are promising potential biomarkers for traumatic HO and ossification of the posterior longitudinal ligament. These findings further emphasize the significant role miRNAs play in the pathogenesis and progression of bone disorders. Repeated investigations into the function of a specific miRNA are infrequent and yield inconsistent results, possibly because of variable experimental conditions. It is hypothesized that miRNAs can enhance osteogenesis for the management of fractures and bone defects. However, further research is required to validate this hypothesis.

Abstract Under the background of global climate change, climate warming has led to an increase in insect herbivory, which significantly affects the growth, survival, and regeneration of forest plants in the warm temperate zone of China. Plants can adopt defense responses to adapt to insect defoliation. Therefore, field experiments were conducted on five common warm temperate species, Quercus acutissima, Quercus serrata, Quercus aliena, Quercus dentata, and Robinia pseudoacacia. We measured the leaf traits of healthy trees and insect defoliated trees, to explore the response strategies of common species in warm temperate zones to insect defoliation. Our results showed that native species stored more carbon in extreme environments for survival rather than growth, while the alien species R. pseudoacacia tended to adopt active resource acquisition strategies and were more inclined towards growth. The content of tannins and flavonoids in the alien species R. pseudoacacia did not significantly increase after leaf damage, while the content of secondary metabolites such as tannins, flavonoids, and total phenols in the native species Q. acutissima, Q. serrata, Q. aliena, Q. dentata increased significantly after leaf damage. This indicated that compared to alien species, native species invested more resources in defense, which might reduce resource allocation for growth. Thus, the native Quercus species have stronger resistance than the alien species R. pseudoacacia after insect defoliation.

In the present study, the interstitial hydrogen (H) atoms were introduced as β-stabilizing element to tailor the microstructure, martensitic phase transition, and functional properties of Ti–V–Al shape memory alloys for biomedical applications. The results revealed that the addition of interstitial H atoms into Ti–V–Al shape memory alloys induced the transition from a single αˊˊ martensite to the coexistence of β parent phase and α phase, regardless of H content. Moreover, the amount of α phase firstly increases and then decreases in the present Ti–V–Al based shape memory alloy with H content increasing. Besides, H addition resulted in larger lattice distortion, further causing the formation of nano-domains in Ti–V–Al based alloys. Besides, no endothermic and exothermic peaks were detected due to the confinement of α-phase, and the emergence of nano-domains. With increasing H atoms content, the mechanical properties such as fracture strength, hardness, recoverable strain for Ti–V–Al based shape memory alloys initially increased and then decreased. (Ti–13V–3Al)99.2H0.8 shape memory alloys exhibited the highest fracture strength of 862 MPa, superior hardness of 307HV, and the fully recoverable strain under 6% pre-strain as well as the moderate elastic modulus, which was mainly attributed to the solution strengthening of interstitial H atoms and the precipitation strengthening of α phase. The best corrosion resistance of Ti–V–Al based shape memory alloys was observed with the 2.0 at. % H, which was due to the formation of TiO2, Ti2O3 oxide films. Moreover, the best wear resistance with the lower wear rate of 0.9347 × 10−6 mm3/N mm was obtained in (Ti–13V–3Al)99·2H0.8 shape memory alloy, due to the integrated effects of higher microhardness, reinforcing effect of α phase and lubrication effect of the hydrogenated film.

Abstract Background Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life. Methods This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life. Discussion If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications. Trial registration NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.

Abstract Purpose This study aimed to evaluate the neurological outcomes of Metastatic epidural spinal cord compression (MESCC) patients who underwent decompressive surgery after experiencing over 48 h of paralysis. Methods This retrospective study hypothesizes that, unlike in cases of trauma and degenerative disorders where delayed decompression surgery often leads to poor outcomes, delayed decompression surgery for MESCC-induced paralysis yields relatively favorable results. This study included MESCC patients who had been paralyzed for more than 48 h and underwent decompressive surgery between January 2012 and December 2020. Data collected mainly included patient demographics, tumor pathologies, neurological function (Frankel grades), ambulatory status, and imaging manifestions. The primary outcome measure was neurological recovery. Results A total of 37 patients were included, with a median preoperative paralysis duration of 9 days. Following decompressive surgery, 30 patients (81.1%) improved by at least one Frankel grade. Specifically, 22 patients (59.5%) regained ambulatory ability. The percentages of patients with Frankel grades A, B, and C who regained ambulation after surgery were 28.6% (2 out of 7), 57.1% (8 out of 14), and 75.0% (12 out of 16), respectively. Conclusions Decompressive surgery is associated with significant neurological recovery in MESCC patients who have been non-ambulatory for more than 48 h. Surgical intervention remains beneficial even in cases of prolonged paralysis.

Al–Mg-Sc-Zr alloys with flat surface, low porosity and excellent mechanical properties were prepared by Laser Metal Deposition (LMD) and annealed (A) using secondary recycled Al–Mg-Sc-Zr powders in an open environment. The optimal LMD parameters are laser power 1800 W, scanning speed 5 mm/s and scanning spacing 3 mm The Al–Mg-Sc-Zr alloy deposited by multi-layer multi-track under optimal parameters and subsequent annealing treatment displays a flat surface, porosity of 2.08%, hardness of 134 HV, ultimate tensile strengthen (UTS) of 348 MPa, yield strength (YS) of 235 MPa and uniform elongation (εu) of 16.71%. The porosity mainly concentrates in the molten pool overlap due to the influence of Marangoni convection. Solute redistribution and compositional subcooling lead to periodic segregation of Sc elements, finally contributing to the appearance of bright and dark spiral stacking features centered in the molten pool. Due to the small G/R value of the molten pool, coarse and fine equiaxed grains are alternately developed during single-track deposition. The in-situ heat treatment induced by the subsequent multi-layer multi-track deposition transformed the alternately distributed coarse and fine equiaxed grain structure into a homogeneous grain structure. This results from the combination influence of the difference in the proportion of large-angle grain boundaries occupied by the coarse/fine grains and the pinning of the Al3(Sc,Zr) grains. The strength of the present alloy is mainly provided by solid solution strengthening, fine grain strengthening and second phase strengthening. The stress concentration is reduced for fine grain size and the intergranular strain transfer is favored because of small internal orientation difference. Meanwhile, the interlayer retention and annealing treatment timely release the thermal stresses during the LMD process, which results in the Al–Mg-Sc-Zr alloys keep good plasticity.

Abstract Background Clinically important lineages in Klebsiella, especially those expressing multi-drug resistance (MDR), pose severe threats to public health worldwide. They arose from the co-evolution of the vertically inherited core genome and horizontal gene transfers by plasmids, which has not been systematically explored. Methods We designed KleTy, which consists of dedicated typing schemes for both the core genome and plasmids in Klebsiella. We compared the performance of KleTy with many state-of-the-art pipelines using both simulated and real data. Results Employing KleTy, we genotyped 33,272 Klebsiella genomes, categorizing them into 1773 distinct populations and predicting the presence of 87,410 plasmids from 837 clusters (PCs). Notably, Klebsiella is the center of the plasmid-exchange network within Enterobacteriaceae. Our results associated the international emergence of prevalent Klebsiella populations with only four carbapenem-resistance (CR) PCs, two hypervirulent PCs, and two hvCR-PCs encoding both carbapenemase and hypervirulence. Furthermore, we observed the ongoing international emergence of bla NDM, accompanied by the replacement of the previously dominant population, bla KPC-encoding HC1360_8 (CC258), during 2003–2018, with the emerging bla NDM-encoding HC1360_3 (CC147) thereafter. Additionally, expansions of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKP) were evidenced in both populations, driven by plasmids of MDR-hypervirulence convergences. Conclusions The study illuminates how the global genetic landscape of Klebsiella has been shaped by the co-evolution of both the core genome and the plasmids, underscoring the importance of surveillance and control of the dissemination of plasmids for curtailing the emergence of hvCRKPs.

AZ31 Mg alloy thin walls are prepared using wire arc additive manufacturing (WAAM) and interlayer ultrasonic impact (UI) techniques with cold metal transition (CMT) serving as the heat source. The microstructure, mechanical and corrosion properties of thin walls prepared by WAAM and WAAM + UI are studied. Results showed that the recrystallization area fraction along traveling direction (TD) increased by 68.6% after UI treatment, and many fine equiaxed crystals were formed, resulting in grain refinement, anisotropy reduction, mechanical and corrosion properties improvement. The average grain size along TD decreased from 66.6 ± 3.5 μm to 32.7 ± 1.6 μm. Through UI treatment, the ultimate tensile strength (UTS) and elongation (EL) along TD increased from 205 MPa to 230 MPa and 13.5%–17%, respectively. The anisotropic percentage of UTS and EL were decreased from 10.8% to 4.5%, and 42.1%–9.7%, respectively. Electrochemical experimental results showed that the average corrosion rate along TD decreased from 1.93 mm year−1 to 1.53 mm year−1. Grain refinement, dislocation density variation and texture strength reduction were the main reasons for these results.

Background: Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation. Methods: We developed an approach to construct injectable hydrogels through a two-step gelation process. In the first step of gelation, the denaturation and rehybridization mechanism of natural biopolymer DNA was utilized to form interconnected structure through hydrogen bonding between complementary base pairs between the DNA strands. In the second step of gelation, the introduction of halloysite nanotubes (HNTs) loaded with osteogenic model drug dexamethasone (Dex) provided additional crosslinking sites through non-covalent interactions with the DNA backbone, including electrostatic interaction and hydrogen bonding interaction. Results: The DNA-based nanocomposite hydrogel material developed in our work can be used as an injectable filling material for the repair of non-load bearing bone defect and can be loaded with osteogenic model drug dexamethasone (Dex) for improved osteoinductivity, promoting new bone regeneration in vivo. Translational potential of this article: This article highlights the potential of using nanocomposite hydrogels to repair non-load bearing bone defects, which are common injuries in the clinic. This study provides a deeper understanding of how to optimize the properties of hydrogels to regulate cell differentiation and tissue formation.

The relentless rise in heart disease incidence, a leading global cause of death, presents a significant public health challenge. Precise prediction of heart disease risk and early interventions are crucial. This study investigates the performance improvement of heart disease prediction models using machine learning and deep learning algorithms. Initially, we utilized the Heart Failure Prediction Dataset from Kaggle. After preprocessing to ensure data quality, three distinct feature engineering techniques were applied: PCA for dimensionality reduction, ET for feature selection, and Pearson's correlation coefficient for feature selection. We assessed their impact on model performance. The dataset was then partitioned into three different data split ratios—1:9, 2:8, and 3:7—to determine their specific effects on model performance. Twelve machine learning classifiers—LGBM, Adaboost, XGB, RF, DT, KNN, LR, GNB, ET, SVC, GB, and Bagging—were trained and evaluated based on five key metrics: accuracy, recall, precision, F1 score, and training time. The influence of different feature engineering methods and data partitioning ratios on model performance were systematically analyzed using paired-sample t-tests. Among the feature engineering methods compared, the Bagging classifier, when combined with feature selection via ET, exhibited superior performance. It achieved an accuracy of 97.48 % and an F1-Score of 97.48 % with a data split ratio of 1:9 between the test and training sets. With a 2:8 split, the accuracy was 94.96 % and the F1-Score was 94.95 %. For a 3:7 split, the accuracy was 94.12 % and the F1-Score was 94.11 %. Paired sample T-test results indicate that feature selection using Pearson correlation coefficient can shorten training duration, but this also leads to a decline in classifier performance. After applying PCA dimensionality reduction, compared with the control group, there was no significant difference in the training efficiency and efficacy of the classifier. However, feature selection through ET significantly reduced the training time for various classifiers while ensuring their performance.

Abstract Background Accurately identifying effective biomarkers and translating them into clinical practice have significant implications for improving clinical outcomes in hepatocellular carcinoma (HCC). In this study, our objective is to explore appropriate methods to improve the accuracy of biomarker identification and investigate their clinical value. Methods Concentrating on the N6-methyladenosine (m6A) modification regulators, we utilized dozens of multi-omics HCC datasets to analyze the expression patterns and genetic features of m6A regulators. Through the integration of big data analysis with function experiments, we have redefined the biological roles of m6A regulators in HCC. Based on the key regulators, we constructed m6A risk models and explored their clinical value in estimating prognosis and guiding personalized therapy for HCC. Results Most m6A regulators exhibit abnormal expression in HCC, and their expression is influenced by copy number variations (CNV) and DNA methylation. Large-scale data analysis has revealed the biological roles of many key m6A regulators, and these findings are well consistent with experimental results. The m6A risk models offer significant prognostic value. Moreover, they assist in reassessing the therapeutic potential of drugs such as sorafenib, gemcitabine, CTLA4 and PD1 blockers in HCC. Conclusions Our findings suggest that the mutual validation of big data analysis and functional experiments may facilitate the precise identification and definition of biomarkers, and our m6A risk models may have the potential to guide personalized chemotherapy, targeted treatment, and immunotherapy decisions in HCC.

The increasing frequency of cervical and lumbar spine disorders, driven by aging and evolving lifestyles, has led to a rise in spinal surgeries using pedicle screws. Robotic spinal surgery systems have emerged as a promising innovation, offering enhanced accuracy in screw placement and improved surgical outcomes. We focused on literature of this field from the past 5 years, and a comprehensive literature search was performed using PubMed and Google Scholar. Robotic spinal surgery systems have significantly impacted spinal procedures by improving pedicle screw placement accuracy and supporting various techniques. These systems facilitate personalized, minimally invasive, and low‐radiation interventions, leading to greater precision, reduced patient risk, and decreased radiation exposure. Despite advantages, challenges such as high costs and a steep learning curve remain. Ongoing advancements are expected to further enhance these systems' role in spinal surgery.

Abstract Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

Abstract In this paper, the effect of rotation speed on the grinding process during the high-speed diamond drilling was studied by considering the metal matrix/rock chips interface. The results showed that when the grinding enters the Phase 3 (three-body wear among diamond, matrix, and rock cuttings), the weight-on-bit and frictional force exhibited significant periodicity. The two-body grinding process (Phase 1 and 2) was converted into a three-body grinding process (Phase 3). The results of the microscopic showed that the depth of each revolution became shallower, and the increasing proportion of primary chip was higher than that of the secondary chip as the speed increased at Phase 3. The increasing the rotational speed promotes the generation of primary chips and inhibits brittle fracture.

Abstract Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations.

Abstract Background The Access, Watch, and Reserve (AWaRe) classification of antibiotics was a useful tool to support antibiotic stewardship. However, the AWaRe patterns of antibiotic consumption in Western China were unclear. We aimed to assess the antibiotic consumption patterns using the AWaRe Classification of public hospitals in Sichuan Province Western China. Methods Antibiotic consumption data of year 2020 were obtained from the Sichuan Province Drug Use Monitoring Platform. We measured the antibiotic consumption (DDDs per 1,000 inhabitants per day, DIDs), calculated the proportion of antibiotic use, the ratio of Access to Watch antibiotics and patterns of antibiotic use by using drug utilization 90%. Results This analysis included 4452 public health institutions. The antibiotic consumption rate was 10.39 DIDs (Median 8.50, IQR 7.71–12.96). The proportions of Access antibiotic use and Watch antibiotic use were 46.83% (Median 47.49, IQR 44.16–52.02) and 51.20% (Median 51.43, IQR 45.42–54.61), respectively. The Access-to-Watch index was 0.91 (Median 0.92, IQR 0.81–1.15). Amoxicillin (16.85%), cefuroxime (9.21%), cefixime (8.60%%), levofloxacin (8.11%) and metronidazole (6.16%) were the most consumed antibiotics. Conclusions The proportion of Access antibiotic consumption in Sichuan Western China has not achieved the WHO target of 60%. Overuse of antibiotic is serious in Sichuan. National and regional antibiotics management systems, stewardship programs and surveillance of antibiotic consumption based on AWaRe classification are needed to improve antibiotic consumption patterns, curb antibiotic overuse and combat antimicrobial resistance in Western China.

Abstract Background Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings. Methods Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP). Results The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029). Conclusion The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants’ outcomes by facilitating timely clinical decisions.

Abstract Purpose Uveal melanoma (UM) is adults’ most common primary intraocular malignant tumor. It has been observed that 40% of patients experience distant metastasis during subsequent treatment. While there exist multigene models developed using machine learning methods to assess metastasis and prognosis, the immune microenvironment’s specific mechanisms influencing the tumor microenvironment have not been clarified. Single-cell transcriptome sequencing can accurately identify different types of cells in a tissue for precise analysis. This study aims to develop a model with fewer genes to evaluate metastasis risk in UM patients and provide a theoretical basis for UM immunotherapy. Methods RNA-seq data and clinical information from 79 μm patients from TCGA were used to construct prognostic models. Mechanisms were probed using two single-cell datasets derived from the GEO database. After screening for metastasis-related genes, enrichment analysis was performed using GO and KEGG. Prognostic genes were screened using log-rank test and one-way Cox regression, and prognostic models were established using LASSO regression analysis and multifactor Cox regression analysis. The TCGA-UVM dataset was used as internal validation and dataset GSE22138 as external validation data. A time-dependent subject work characteristic curve (time-ROC) was established to assess the predictive ability of the model. Subsequently, dimensionality reduction, clustering, pseudo-temporal analysis and cellular communication analysis were performed on GSE138665 and GSE139829 to explore the underlying mechanisms involved. Cellular experiments were also used to validate the relevant findings. Results Based on clinical characteristics and RNA-seq transcriptomic data from 79 samples in the TCGA-UVM cohort, 247 metastasis-related genes were identified. Survival models for three genes (SLC25A38, EDNRB, and LURAP1) were then constructed using lasso regression and multifactorial cox regression. Kaplan-Meier survival analysis showed that the high-risk group was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Time-dependent ROC curves demonstrated high predictive performance in 6 m, 18 m, and 30 m prognostic models. Cell scratch assay showed that the 24 h and 48 h migration rates of cells with reduced expression of the three genes were significantly higher than those of the si-NC group. CD8 + T cells may play an important role in tumour metastasis as revealed by immune infiltration analysis. An increase in the percentage of cytotoxic CD8 + T cells in the metastatic high-risk group was found in the exploration of single-cell transcriptome data. The communication intensity of cytotoxic CD8 was significantly enhanced. It was also found that the CD8 + T cells in the two groups were in different states, although the number of CD8 + T cells in the high-risk group increased, they were mostly in the exhausted and undifferentiated state, while in the low-risk group, the CD8 + T cells were mostly in the functional state. Conclusions We developed a precise and stable 3-gene model to predict the metastatic risk and prognosis of patients. CD8 + T cells exhaustion in the tumor microenvironment play a crucial role in UM metastasis.

Introduction Acute sleep and circadian rhythm (SCR) disruption can lead to a range of negative physical and mental consequences, such as depression, delirium, respiratory dysfunction and increased mortality. In the intensive care unit (ICU), the unique environment can exacerbate disruptions in SCR. Few studies have identified the characteristics of SCR in the ICU, and the roles of patient characteristics, illness and medical interventions in ICU SCR remain unclear. A single-centre prospective cohort study, called SYNC study (Sleep and circadian rhYthm in iNtensive Care unit), will be conducted to explore the characteristics and associated factors of SCR and investigate the short-term prognosis among patients in the surgical ICU.Methods and analysis Patients from a surgical ICU at a tertiary teaching hospital will be enrolled. SCR will be assessed by both objective and subjective indicators, including melatonin secretion rhythm, activity rhythm, sleep pattern and perceived sleep quality. Data on eight potential factors that influence SCR, including light exposure, noise level, pain level, nighttime disturbances, mechanical ventilation, sedative and analgesic use, meal pattern and restraints, will be collected. These data will be gathered in the first 3 days after ICU admission. Short-term prognostic indicators, including anxiety, depression, cognitive function, insomnia, activities of daily living, ICU stay, hospital stay and hospital mortality will be collected during the hospital stay and at 1 month after discharge.Ethics and dissemination The study has been approved by the Ethics Committee of Zhongshan Hospital, Fudan University (B2024-076R). The results of this study will be published in peer-reviewed journals.Trial registration number NCT06346613.

Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality, and while the association between the urinary albumin-to-creatinine ratio (UACR) and cardiovascular risk is recognized, the specific impact of UACR on the long-term survival of ASCVD patients remains not fully understood. The aim of this study is to investigate the influence of UACR on the long-term risk of all-cause mortality in patients with ASCVD. Methods: This study included ASCVD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Mortality outcomes were ascertained by linkage to the National Death Index as of December 31, 2019. UACR risk was stratified into three levels: Group 0 (UACR < 30 mg/g), Group 1 (30–300 mg/g), and Group 2 (>300 mg/g). The primary outcome was all-cause mortality, with cardiovascular mortality as a secondary outcome. Cox proportional hazards, adjusted for demographic factors, traditional cardiovascular risk factors, and secondary prevention medications for ASCVD, were used to analyze the cumulative risk of outcomes. Propensity score matching was employed for risk adjustment, and sensitivity analyses were conducted based on cohorts with chronic coronary syndrome (CCS), stroke, heart failure, and non-heart failure. Results: Among the 1,737 patients with a median follow-up of 10 years, 1,026 all-cause deaths and 351 cardiovascular deaths were recorded. After full model adjustment, higher UACR levels were associated with increased risks of all-cause mortality (Group 1: hazard ratio (HR), 1.601; 95 % confidence interval (CI), 1.382–1.855; Group 2: HR, 2.378; 95 % CI, 1.884–3.001; both P < 0.001 for trend) and cardiovascular mortality (Group 1: HR, 2.080; 95 % CI, 1.631–2.652; Group 2: HR, 2.883; 95 % CI, 1.951–4.260; both P < 0.001 for trend). Propensity score matching confirmed these findings, showing significantly elevated all-cause mortality risks in high-risk UACR groups (with a cutoff of 30 mg/g: HR, 1.468 (95 %CI, 1.254–1.719), P < 0.001; with a cutoff of 300 mg/g: HR, 1.935 (95 %CI, 1.399–2.675), P < 0.001). All sensitivity analyses were consistent with the results of the overall cohort. Conclusion: UACR is an important prognostic indicator for predicting the long-term outcomes of ASCVD patients, with its impact being independent of eGFR.

IntroductionBreast cancer is currently the most prevalent cancer globally; however, it generally has a favorable prognosis and is linked to a high survival rate. While effective treatments can extend survival and mitigate associated side effects, not all survivors are exempt from complications. Notably, a significant proportion of survivors experience sleep disorders following surgery, which can severely impact their quality of life. Exercise is frequently recommended as a non-pharmacological intervention to enhance sleep quality among breast cancer survivors and may also play a role in reducing recurrence rates. Recognizing that various forms of exercise may yield different outcomes in addressing sleep disorders in this population, we conducted a network review meta-analysis to assess the effectiveness of diverse exercise modalities for breast cancer survivors suffering from sleep disturbances.MethodsWe searched four electronic databases for randomized controlled trials of individuals diagnosed breast cancer with sleep disorders by different exercise therapy. The primary outcomes included Yoga, Pilates, Qigong, Tai Chi, Walking, Dance, Resistance training, Football, Virtual reality therapy, Activity change exercise, Software-guided exercises. The methodological quality of the included studies was assessed using the Cochrane Bias risk Assessment tool, and network meta-analysis was performed using Stata15 software. The review was pre-registered (PROSPERO ID: CRD42023442892).ResultsData on 3083 breast cancer survivors with sleep disturbances from 34 eligible randomized controlled trials were analyzed, with 23 classified as medium risk and 2 as high risk. Network meta-analysis showed that walking exercise [Standard Median Different (SMD) =3.06, 95% Confidence Interval (95%CI)=(-5.89,-0.23)] significantly improved sleep disorder (Surface Under the Cumulative Ranking curve, SUCRA: 84.5%) and reduced Pittsburgh sleep quality index (PSQI) score.DiscussionBased on the network ranking table, we can conclude that walking exercise offers greater benefits compared to other exercise interventions for improving sleep quality in breast cancer patients. This finding presents a novel perspective on exercise interventions for breast cancer survivors experiencing sleep disorders.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=442892, identifier CRD42023442892.

ObjectivesAcute respiratory distress syndrome (ARDS) is associated with high rates of morbidity and mortality. However, the evidence regarding the effectiveness of commonly used treatments, including corticosteroids, neuromuscular blocking agents (NMBAs), and inhaled nitric oxide (iNO), remains uncertain. Therefore, this study aimed to compare and rank these three treatments to identify the most effective option.Data sourcesWe searched PubMed, Embase, Cochrane Library, and Web of Science for clinical trials from the earliest records to 1 May 2024.Study selection and data extractionClinical trials evaluating three interventions compared with the control group for ARDS were included, with restrictions on any language. Data were extracted by two independent reviewers. Frequentist network meta-analysis (NMA) was performed to identify the most effective intervention, and treatments were ranked using the surface under the cumulative ranking (SUCRA) curve. The primary outcome was 28-day mortality, while secondary outcomes included ventilator-free days up to 28 days, ICU mortality, in-hospital mortality, and the incidence of new infection events.Data synthesisData from 26 clinical trials encompassing 5,071 patients were analyzed. Vecuronium bromide was the most effective strategy for reducing 28-day mortality compared to conventional treatment, iNO, methylprednisolone, and placebo (OR 0.38, 95% CI 0.15–1.00, and OR 0.30, 95% CI 0.10–0.85 and OR 0.25, 95% CI 0.08–0.74 and OR 0.23, 95% CI 0.08–0.65; SUCRA: 96.6%). Dexamethasone was identified as the most effective treatment option for increasing ventilator-free days at 28 days compared to conventional therapy and cisatracurium (MD 3.60, 95% CI 1.77–5.43, and MD 3.40, 95% CI 0.87–5.92; SUCRA: 93.2%). Methylprednisolone demonstrated the highest effectiveness for preventing ICU mortality (SUCRA: 88.5%). Although dexamethasone, cisatracurium, conventional therapy, methylprednisolone, and iNO treatment did not show significant superiority in reducing in-hospital mortality, dexamethasone showed the highest probability of being the most effective treatment option (SUCRA: 79.7%). Furthermore, dexamethasone treatment showed the highest safety in reducing the incidence of new infection events compared with placebo and iNO (OR 0.61, 95% CI 0.42–0.88, and OR 0.33, 95% CI 0.19–0.58; SUCRA: 91.8%).ConclusionThis NMA suggests that corticosteroids may provide benefits to patients with ARDS. While the application of NMBAs may reduce 28-day mortality, iNO did not demonstrate a significant beneficial effect as a therapeutic measure.Systematic review registrationPROSPERO, CRD42022333165 https://www.crd.york.ac.uk/PROSPERO/.

The ecological changes triggered by rapid urbanization pose a significant threat to the balance of supply and demand for recreational ecosystem services. Understanding the spatial and temporal processes of Recreational Ecosystem Services (RES) supply–demand matching and their driving mechanisms is essential for the enhancement of human well-being and the sustainable management of socio-ecological systems in the region. Taking the Yangtze River Delta Urban Agglomeration in China as an example, this study first builds an updated supply indicator system based on the four dimensions and examines the supply, demand, and matching of RES in the region with the help of heterogeneous data from multiple sources. We also examine the spatio-temporal processes and spatial spillover effects of supply–demand matching, as well as the nonlinearity and spatial non-stationarity of the role of the driving factors. The results show that the supply level of RES is generally low, but is on an upward trend. There are significant spatial differences in the demand level, and the matching level is declining with significant polarisation. The matching types generally show a trend of decreasing L-L and M-L and a significantly increasing H-H. The changes in supply and demand risks at different levels are dominated by level-by-level migration, but the low-level units attract the higher level to leap downward across level transitions, thus indicating a significant spatial spillover effect. The regression model estimation showed a decrease in the contribution of ecological factors and an enhancement of socio-economic factors. Each factor exhibits different degrees of non-linear marginal effects. The regression coefficients were significantly heterogeneous in space. Finally, the influence processes of county-level and city-level drivers were discussed, and the establishment of a three-level transmission mechanism of “grid-county-city” was proposed to achieve the sustainable management of recreational resources.

IntroductionThe coupling and coordination development level (CCDL) of science and technology innovation (STI) between universities and enterprises is a key determinant of the effectiveness of the national STI system.MethodsThis study utilized data from universities and industrial enterprises spanning from 2012 to 2021 to establish an indicator system for measuring university STI ability and enterprise STI ability. The study then applied the entropy TOPSIS method to calculate the STI scores and further analyzed them using a coupling coordination model. Various research methods were employed to quantify the spatiotemporal characteristics and elucidate the patterns of evolution, with the grey relational analysis model being utilized to examine the mutual influence at the micro-index level.Results and discussionThe study found a significant transformation in the collaboration between universities and enterprises in China, shifting from extreme incoherence to highly coordinated cooperation. Secondly, the reason for the differences is the uneven development in the four regions. Thirdly, the CCDL of STI between universities and enterprises in each region is notably different, but all show σ convergence trend. Finally, the university STI ability and enterprise STI ability are identified as key factors in the CCDL of STI between universities and enterprises.

Abstract The storm‐time temperature difference with respect to its quiet‐time expectation (ΔT) in the mesosphere and lower thermosphere were studied during the extreme storms on 2024 Mother's Day and 2003 Halloween Day. The storm‐time ΔT were determined by performing daily zonal running mean on the temperature profiles in the ascending and descending nodes separately. The storm‐time ΔT had peak values of ≥25 K and extended downward to ∼100 km globally. Above 105 km, the global mean ΔT had values of ≥20 K in the early morning and of ≥15 K in the late afternoon during storm‐time. At high latitudes, the storm‐time ΔT was larger in the late afternoon than in the early morning. This is opposite to that at middle and low latitudes. Adiabatic warming/cooling caused by the heating‐induced circulation changes outside of the auroral oval is likely responsible for the local time and latitude dependence of the storm‐time ΔT.

Background: Early-onset ischemic heart disease (IHD) is a growing burden associated with high disability and death. Objectives: This study aimed to estimate the burden of incidence, prevalence, and disability-adjusted life years (DALY) of early-onset IHD from 1990 to 2019. Methods: Data on the burden of early-onset IHD (men

The presence of Hg2+ causes substantial stress to plants, adversely affecting growth and health by disrupting cell cycle divisions, photosynthesis, and ionic homeostasis. Accurate visualization of the spatiotemporal distribution of Hg2+ in plant tissues is crucial for the management of Hg pollution; however, the related research is still at its early stage. Herein, a small-molecule amphiphilic fluorescent probe (termed LJTP2) was developed for the specific detection of Hg2+ with a high sensitivity (~16 nM). Fluorescent imaging applications with LJTP2 not only detected the dynamic distribution of Hg2+ within plant cells at the subcellular level but also enabled the understanding of cell membrane health under Hg2+ stress. This study introduces a valuable imaging tool for elucidating the molecular mechanism of Hg2+ stress in plants, demonstrating the potential of the application of small-molecule fluorescent probes in plant science.

Abstract Vertical field effect transistor (VFET), in which the semiconductor is sandwiched between source/drain electrodes and the channel length is simply determined by the semiconductor thickness, has demonstrated promising potential for short channel devices. However, despite extensive efforts over the past decade, scalable methods to fabricate ultra-short channel VFETs remain challenging. Here, we demonstrate a layer-by-layer transfer process of large-scale indium gallium zinc oxide (IGZO) semiconductor arrays and metal electrodes, and realize large-scale VFETs with ultra-short channel length and high device performance. Within this process, the oxide semiconductor could be pre-deposited on a sacrificial wafer, and then physically released and sandwiched between metals, maintaining the intrinsic properties of ultra-scaled vertical channel. Based on this lamination process, we realize 2 inch-scale VFETs with channel length down to 4 nm, on-current over 800 A/cm2, and highest on-off ratio up to 2 × 105, which is over two orders of magnitude higher compared to control samples without laminating process. Our study not only represents the optimization of VFETs performance and scalability at the same time, but also offers a method of transfer large-scale oxide arrays, providing interesting implication for ultra-thin vertical devices.

In the present study, the influence of training on the microstructural evolution, martensitic transformation behavior and mechanical/functional properties of Ti–V–Al–Zr shape memory alloy was investigated systematically. With the increasing of training cycling number, the degree of martensite reorientation became larger and larger. Moreover, higher density of dislocations appeared in the interior of martensite variants, upon the excessive training cycling number was applied. The international stress can be brought into the matrix, which not only promoted to the ω→αˊˊ transition, but also made the martensite phase stabilizer and even suppressed the αˊˊ→β martensitic transformation during training process. The superior mechanical properties including maximum fracture stress of 906 MPa and the higher fracture strain of 33.6% can be obtained in Ti–V–Al–Zr shape memory alloy subjected with the training cycles number of 5th, which can be attributed to the matrix strengthening stemmed from work hardening and suppression of ω precipitation. Meanwhile, the lower critical stress for the martensite variant reorientation and enhanced matrix strength synergistically contributed to the superior strain recovery characteristics with total completely recoverable strain of 6% in Ti–V–Al–Zr shape memory alloy by controlling training cycles number of 5th. Meanwhile, the higher micro-hardness can be obtained by training.