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Traditional L2 pronunciation teaching puts too much emphasis on explicit phonological knowledge ('knowing that') rather than on procedural knowledge ('knowing how'). The advancement of mobile-assisted language learning (MALL) offers new opportunities for L2 learners to proceduralize their declarative articulatory knowledge into production skills more efficiently through systematic practice. Within the framework of skill acquisition theory, and using a mixed-methods design including production tests, articulatory awareness quizzes, and a semi-structured interview, this study aims to investigate the effectiveness of using an augmented reality (AR) filter app during pronunciation practice to improve Chinese L2 students' segmental production and articulatory awareness of the targeted English consonants (dark/[voiced velarized alveolar approximant]/,/[voiced dental fricative]/and/[voiceless dental fricative]/), and their attitudes towards this application. The experimental results indicate that the app with AR technology, facial detection technology, and digital zoom technology played a positive role in promoting students' segmental production and raising their articulatory awareness. The interview results show that the AR filter helped to alleviate the learners' speaking anxiety and embarrassment related to interacting with the teacher for corrective feedback, and encouraged daily practice by providing more fun. Combining all the qualitative and quantitative results, we conclude that an AR filter app can offer academic, psychological, and social support for L2 pronunciation skill learning.

Abstract At present, biopharmaceuticals have received extensive attention from the society, among which recombinant proteins have a good growth trend and a large market share. Chinese hamster ovary (CHO) cells are the preferred mammalian system to produce glycosylated recombinant protein drugs. A highly efficient and stable cell screening method needs to be developed to obtain more and useful recombinant proteins. Limited dilution method, cell sorting, and semi-solid medium screening are currently the commonly used cell cloning methods. These methods are time-consuming and labor-intensive, and they have the disadvantage of low clone survival rate. Here, a method based on semi-solid medium was developed to screen out high-yielding and stable cell line within 3 weeks to improve the screening efficiency. The semi-solid medium was combined with an expression vector containing red fluorescent protein (RFP) for early cell line development. In accordance with the fluorescence intensity of RFP, the expression of upstream target gene could be indicated, and the fluorescence intensity was in direct proportion to the expression of upstream target gene. In conclusion, semi-solid medium combined with bicistronic expression vector provides an efficient method for screening stable and highly expressed cell lines.

Abstract Background Plerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni. Methods In this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults. Results A total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni. Conclusions The dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni. Graphical abstract

To investigate the current landscape of the application of machine learning in remote sensing surveys of geological disasters and to support the development of intelligent remote sensing survey technologies for geological disasters, a bibliometric analysis of machine learning and geological disaster remote sensing survey technology was conducted using the China National Knowledge Infrastructure (CNKI) database. Visual analysis was performed from multiple perspectives, including the number of publications, research hotspots, and research institutions, to describe the research progress of machine learning and geological disaster remote sensing survey technology. VOSviewer software was utilized to scrutinize the high-frequency keywords and their associations between machine learning and geological disaster remote sensing survey technology. The results showed that remote sensing survey technology for geological disasters in China is gradually shifting from traditional “topographic measurement” towards more holistic “topographic and geometric measuremen” approaches. With the advancement of unmanned aerial vehicle remote sensing technology, the new generation of intelligent learning algorithms have emerged as the predominant research direction, fostering the growth of automated geological disaster recognition and intelligent extraction techniques. Nevertheless, the future of remote sensing survey technology for geological disasters is poised to evolve into a comprehensive technical system that emphasizes the synergistic “air-space-ground” application and emergency monitoring. Considering the diverse characteristics of remote sensing image data, the primary developmental trajectory will involve an extensive exploration of various machine learning algorithms across different remote sensing interpretation scenarios.

With the development of arid and semi-arid regions in China, the hazards posed by collapsible sands to engineering construction have become increasingly significant. In order to investigate the collapsibility regularity and its influencing factors of sand soils, this paper focuses on the wind-blown sands at the southern edge of the Maowusu Desert. Initially, by controlling the single factor laboratory compression tests, the collapsibility regularity of wind-blown sand under different working conditions was investigated. Subsequently, using PFC3D (three-dimensional particle flow software) for numerical simulation of the laboratory compression tests on wind-blown sands, the paper explores the effects of different porosities and particle compositions on the collapsibility of sandy soils. The research results indicate that the collapsibility coefficient of sandy soils shows a trend of first increasing and then decreasing with pressure, reaching its maximum value at 150 kPa. With the increase in dry density or moisture content, the collapsibility coefficient of sand decreases. Compared to moisture content, dry density has a greater impact on the collapsibility of sandy soils. There is a positive correlation between the collapsibility coefficient of wind-blown sand and its porosity. The initial porosity of the collapsibility of the wind-blown sand on the southern edge of the Maowusu Desert is 0.425. When the ratio of particle content between 0.075～0.25 mm and 0.25～0.5 mm is 0.35∶0.65, the collapsibility of sandy soils is maximized. The research results comprehensively describe the entire process of laboratory compression tests on sand from macro to micro levels, revealing the collapsibility regularity and its influencing factors on wind-blown sand from multiple scales. This can provide a reference for engineering construction in the Maowusu Desert and provide certain ideas and basis for the research on particle flow numerical simulation of sand.

Abstract Elastocaloric cooling has experienced fast development over the past decade owing to its potential to reshape the refrigeration industry. While the solid-state elastocaloric refrigerant is emission-free, the efficiency of the state-of-the-art elastocaloric cooling systems is not sufficient yet to reduce carbon emissions during operation. In this study, we double the coefficient of performance, the most commonly used efficiency metric, via the synergy of material-level advances in TiNiCu and the system-level roller-driven mechanism capable of recovering kinetic energy. On the materials level, a 125% improvement in coefficient of performance is illustrated in TiNiCu compared to NiTi, empowered by the B2-B19 martensitic transformation with improved lattice compatibility and the grain boundary strengthening from the nanocrystalline structure. On the system level, owing to the properly sized angular momentum in rotating parts, 78% work recovery efficiency is reported, transcending the theoretical limit previously unattainable without kinetic energy recovery. This confluence of materials and mechanical innovations propels elastocaloric cooling systems into a new realm of efficiency and paves the way for their practical application.

Abstract Background Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive. Results We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown. Conclusions Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract

Abstract The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Feature extraction and classification is a difficult area in motor imagery electroencephalogram (EEG) signal processing. In order to improve the classification accuracy of EEG signals, both a feature extraction method based on the combination of LMD-CSP and a classification algorithm based on the fusion of PSO-SVM are proposed. Firstly, the extended informax ICA algorithm is used to denoise the signal and reduce the influence of noise on the signal. Then, the pre-processed EEG signals are decomposed into multiple Product Function (PF) components by Local Mean Decomposition (LMD), and the most discriminative PF component is selected. Next, feature extraction is carried out from the selected PF components using the Common Space Pattern (CSP). Finally, the obtained features are input into a Support Vector Machine (SVM) classifier improved by Particle Swarm Optimization (PSO) for classification recognition. The experimental results show that compared with the traditional CSP-SVM method, CapsNet method, WPT-CSP+CNN method, FDCSP-SVM method, and EMD-CNN method, the classification accuracy of the proposed method is increased by 26.94 %, 14.9 %, 13.34 %, 8.34 % and 4.04 %, respectively. This further proves the superiority of the proposed method for EEG signal processing technology.

This study addresses the pivotal challenge of water resource allocation in urban environments by introducing a novel approach – a multi-objective chance-constrained fuzzy interval linear programming model integrated with principal component analysis (PCA). This innovative model aims to alleviate subjectivity in urban water management processes, particularly in adjusting water demands across various sectors. The proposed model incorporates correlation analysis to identify dimensionality-reducing factors of multitarget components, determining the proportion of each target component relative to the total components. Fuzzy sets are applied to irrigation water resource allocation quantity, segmented into six levels of fuzzy membership to analyze the stochasticity of water supply. Results demonstrate the model's efficacy, revealing that variations in risk probabilities impact water supply, necessitating positive water management strategies to enhance agricultural efficiency and negative strategies to mitigate the risk of inadequate water supply. Key findings emphasize the significance of agricultural water availability and the structure of irrigation water use in optimal resource allocation. Importantly, the study showcases the enhanced precision achieved through the proposed multi-objective chance-constrained fuzzy interval linear programming with PCA, thereby refining the optimization outcomes for water management under multifaceted objectives. HIGHLIGHTS Development of a multi-objective chance-constrained fuzzy interval model.; Integration principal component analysis to improve the optimal solutions.; Application of a multidimensional analysis to effectively assess risk probabilities.; Optimization of agricultural water resources under varying constraints.; Offering strategic recommendations for agricultural cropping structures.;

Abstract Prognostics and health management (PHM) has gotten considerable attention in the background of Industry 4.0. Battery PHM contributes to the reliable and safe operation of electric devices. Nevertheless, relevant reviews are still continuously updated over time. In this paper, we browsed extensive literature related to battery PHM from 2018 to 2023 and summarized advances in battery PHM field, including battery testing and public datasets, fault diagnosis and prediction methods, health status estimation and health management methods. The last topic includes state of health estimation methods, remaining useful life prediction methods and predictive maintenance methods. Each of these categories is introduced and discussed in details. Based on this survey, we accordingly discuss challenges left to battery PHM, and provide future research opportunities. This research systematically reviews recent research about battery PHM from the perspective of key PHM steps and provide some valuable prospects for researchers and practitioners.

Abstract Background and objective Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. Materials and methods Eight formal in-preserved cadaveric pelvises aged 30–50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. Results As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p 0.05). Conclusion For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1-overexpression (Prdx1-OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC0‒t, half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI.

The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources. However, the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment. Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization. In this study, a comprehensive approach combining the ion ratio method, mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area. The findings reveal that: (1) Groundwater samples in study area exhibit a neutral to slightly alkaline pH. The predominant chemical types of unconfined water are HCO3-Ca·Na, HCO3·Cl-Na·Ca and HCO3·SO4-Ca·Na, while confined water mainly exhibits Cl·HCO3-Na and Cl-Na types. (2) Salinity coefficients indicate an increase in salinity from unconfined to confined water. TDS, Na+ and Cl– concentrations show an increasing trend from mountainous to coastal areas in unconfined water, while confined water displays variability in TDS, Na+ and Cl– concentrations. (3) Groundwater salinity is mainly influenced by water-rock interactions, including the dissolution of halite and gypsum, cation exchange, and seawater intrusion etc. Additionally, human activities and carbonate dissolution contribute to salinity in unconfined water. Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water, with increasing cation exchange and seawater interaction observed from unconfined to confined water.

Abstract Background Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response. Methods Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model. Results The gene expression of hundreds of DEGs (FDR p 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p

In recent years, the global practice of regional natural disaster reduction and comprehensive risk prevention has promoted the integration of multiple disciplines, and the theory and technology of comprehensive risk assessment for multiple natural disaster chains urgently need innovation. This article is based on multiple natural disaster chain scenarios and sets secondary indicators for multiple influencing factors based on the first level indicators composed of basic risk factors such as hazard factors, vulnerability of disaster bearing bodies, and disaster prevention and reduction capabilities. By using multidimensional information diffusion technology, multiple hazard factor hazard combination factors, vulnerability combination factors of disaster bearing bodies, and comprehensive disaster prevention and reduction capability combination factors reflecting various natural disaster scenarios are constructed, A household comprehensive risk assessment index system for multi-dimensional information diffusion assessment of natural disaster comprehensive risk was designed by quantifying risk factors such as the intensity of comprehensive disaster causing factors, vulnerability of disaster bearing bodies, and comprehensive disaster prevention and reduction capabilities in disaster scenarios. This paper expands the traditional information diffusion comprehensive risk assessment model, makes up for the lack of information on geographical units, establishes a multi impact factor multi dimension natural disaster risk comprehensive assessment model for multi risk factors of complex disaster scenarios with small samples, obtains the theoretical value of multi-dimensional information Diffusion model comprehensive risk assessment for complex disaster scenarios, breaks through the sample size limit of natural disaster risks, and makes up for the lack of information on small samples of small probability events, Improved the reliability and accuracy of comprehensive risk assessment for multiple natural disaster chains. Then, take the disaster scenario formed by the comprehensive risk of earthquake and flood in a place in the upper reaches of the Fujiang River basin as the analysis sample, calculate the comprehensive risk assessment value of flood and earthquake damage in the study area's micro samples (rural households in villages and towns). By comparison, it is found that the comprehensive risk value assessed by the multi-dimensional information Diffusion model has good reliability and high accuracy, which is significantly better than the traditional Kriging interpolation method and geographical weighted regression method. This article provides a comprehensive risk assessment of natural disasters at the micro household level, which can better reflect the diversity and regionality of risks, help clarify the hidden risks of rural natural disasters, and provide scientific basis for government emergency management decision-making.

Chimonobambusa utilis is a unique edible bamboo species valued for its economic and nutritional benefits. However, its existence in natural habitats is at risk due to environmental shifts and human interventions. This research utilised the maximum entropy model (MaxEnt) to predict potential habitats for Ch. utilis in China, identifying key environmental factors influencing its distribution and analysing changes in suitable habitats under future climate conditions. The results show that the results of the MaxEnt model have high prediction accuracy, with an AUC (Area Under the receiver operating characteristic Curve) value of 0.997. Precipitation in the driest month (Bio14), altitude (Alt) and isothermality (Bio03) emerged as the primary environmental factors influencing the Ch. utilis distribution. Currently, the suitable habitats area for Ch. utilis is 10.55 × 104 km2. Projections for the 2050s and 2090s indicate potential changes in suitable habitats ranging from -3.79% to 10.52%. In general, the most suitable habitat area will decrease and shrink towards higher latitude areas in the future. This study provides a scientific basis for the introduction, cultivation and conservation of Ch. utilis.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

Abstract The global energy budget is pivotal to understanding planetary evolution and climate behaviors. Assessing the energy budget of giant planets, particularly those with large seasonal cycles, however, remains a challenge without long-term observations. Evolution models of Saturn cannot explain its estimated Bond albedo and internal heat flux, mainly because previous estimates were based on limited observations. Here, we analyze the long-term observations recorded by the Cassini spacecraft and find notably higher Bond albedo (0.41 ± 0.02) and internal heat flux (2.84 ± 0.20 Wm−2) values than previous estimates. Furthermore, Saturn’s global energy budget is not in a steady state and exhibits significant dynamical imbalances. The global radiant energy deficit at the top of the atmosphere, indicative of the planetary cooling of Saturn, reveals remarkable seasonal fluctuations with a magnitude of 16.0 ± 4.2%. Further analysis of the energy budget of the upper atmosphere including the internal heat suggests seasonal energy imbalances at both global and hemispheric scales, contributing to the development of giant convective storms on Saturn. Similar seasonal variabilities of planetary cooling and energy imbalance exist in other giant planets within and beyond the Solar System, a prospect currently overlooked in existing evolutional and atmospheric models.

Abstract Background the salutogenic theory is essential to explain an individual’s ability to maintain health during the perinatal period. While previous studies mainly focused on the perspectives from a family-level orientation and a global orientation, the purpose of the present study was to develop and validate a scale, the childbearing sense of coherence scale (CSOC-scale) from the individual’s perceptions of the stresses, resources, and meaningfulness of childbearing. Methods A total of 3 separate studies contributed to the development of the CSOC-scale between July 2022 and February 2023. In study 1, the initial item pool based on the conceptual framework of the childbearing sense of coherence and the salutogenic theory was developed. Delphi expert consultation was conducted to revise and improve items. Studies 2 and 3 were cross-sectional studies. In study 2, item analysis and explore factor analysis (EFA) (N = 351 for women, N = 256 for men) were used to screen items. In study 3, confirmatory factor analysis (CFA) and reliability analysis (N = 366 for women, N = 308 for men) were used to test the fit indices and reliability of the final scale. Results final analysis suggested the CSOC-scale includes three factors, consisting of 13 items. Confirmatory factor analysis demonstrated good model fit (χ 2 = 157.448, df = 62, χ 2 / df = 2.539, RMSEA = 0.065, CFI = 0.974, TLI = 0.968, SRMR = 0.029 for women; χ 2 = 181.363, df = 62, χ 2 / df = 2.925, RMSEA = 0.079, CFI = 0.968, TLI = 0.960, SRMR = 0.033 for men) and high factor loadings (from 0.751 to 0.929 for women; from 0.746 to 0.947 for men). Internal consistency (Cronbach’s α ranging from 0.895 to 0.933 for women and 0.881 to 0.945 for men in three dimensions; Cronbach’s α was 0.919 for women and 0.821 for men in the entire instrument) and split-half reliability (Spearman-Brown coefficients ranging from 0.876 to 0.921 for women and 0.841 to 0.937 for men in three dimensions; Spearman-Brown coefficient was 0.744 for women and 0.785 for men in the entire instrument) were excellent. Conclusions the CSOC-scale has robust psychometric properties. It is reliable and valid in evaluating the childbearing sense of coherence in women and men during pregnancy. Utilisation of this scale can help healthcare professionals understand the health maintenance competencies of couples during the transition of parenthood and provide health promotion services from a salutogenic perspective.

Abstract CD7 targeted CAR‐T has demonstrated potential in the treatment of T cell malignancies but no study has been reported about its potential in the prophylaxis of GVHD in allo‐HSCT. Here we reported a special case that a boy diagnosed with refractory acute T lymphoblastic leukemia (T‐ALL) was treated with universal CD7 targeted CAR‐T (CD7 UCAR‐T) and parent‐derived peripheral blood stem cells (PBSCs). Complete remission and full engraftment of donor was observed. In the later four months of follow‐up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR‐T in the prophylaxis of GVHD.

Abstract Background Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. Methods Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. Results From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1–77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6–14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3–83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3–4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5–1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. Conclusions Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. Trial Registration ClinicalTrials.gov, NCT03781219.

Abstract Background To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. Methods We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. Results The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010–2019. The burdens of five categories of disease causes – cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases – were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Corrosion poses a significant threat to the structural integrity of steel rails, especially in an acidic environment. In this study, we evaluate the corrosion properties of U75V-welded joints using potentiodynamic polarization curves, electrochemical impedance measurements, and corrosion morphology studies under simulated acidic conditions. Compared to non-normalized joints, the normalized joints exhibit a higher self-corrosion current (4.65 × 10−5 A/cm2) and a more negative self-corrosion potential (−0.56919 mV). The smaller and more uniform grain size obtained after normalizing provides multiple active sites on the surface for polarization reactions. Furthermore, owing to significant erosion caused on the rail surface by the acidic solutions, normalizing treatment enhances the passivation effects on the surface, resulting in increased corrosion resistance (221.96 Ω cm2). Our findings provide insights into the impact of normalizing treatments on the corrosion mechanism of U75V rail joints under acidic conditions.

Abstract Background The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. Methods We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi’s world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan–Meier method. Results From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70–74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. Conclusions This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.

Abstract N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. With a favorable bioavailability of 24.0%, N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

Agrobacterium-mediated plant transformation is widely used in plant genetic engineering. However, its efficiency is limited by plant immunity against Agrobacterium. Chili pepper (Capsicum annuum L.) is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation. In this work, Agrobacterium was found to induce a strong immune response in pepper, which might be the reason for T-DNA being difficult to express in pepper. An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves. Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death, presumably due to reduced bacterial growth. However, mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response. The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.

Objective To evaluate safety and efficacy of linaclotide combined with polyethylene glycol(PEG) for bowel preparation. Methods A total of 612 patients from Department of Gastroenterology at the Affiliated Hospital of Qingdao University for colonoscopy examination from January to June 2023 were selected. They were divided into group 1(1 L PEG+2 L PEG), group 2(linaclotide+2 L PEG) and group 3(1 L PEG+linaclotide+1 L PEG) by random number table method, with 204 cases in each group. The Ottawa Bowel Preparation Quality Scale(OBPS), the insertion time of colonoscopy, the time of the first defecation, the frequency of defecations, the occurrence of adverse effects and patients' tolerability were compared among the three groups. Results A total of 601 patients completed bowel preparation and accepted colonoscopy. Group 1 exhibited no statistically significant differences to group 2 with regards to OBPS and insertion time. However, Group 2 demonstrated a shorter duration for the time of the first defecation in comparison to both group 1 and group 3(P＜0.05). Group 1 displayed a higher frequency of defecations as compared to Group 2 and Group 3(P＜0.05) . The incidence of adverse reactions was significantly lower in group 2 and group 3 than in group 1(P＜0.05). The overall tolerance score of patients in group 1 was lower than that in group 2 and group 3(P＜0.05). Conclusions The effect of combining 2 L PEG with 290 μg of linaclotide for bowel preparation before colonoscopy is similar to that of 3 L PEG. It can reduce the incidence of adverse reactions and patients exhibit good tolerance. For patients who are intolerant to a single high-dose administration of PEG, they need divided-dose regimen of 2 L PEG in combination with linaclotide.

Titanium alloys have excellent properties and are widely used in aerospace, medicine, chemical industry, and other fields. With the rapid development of the powder metallurgy and 3D printing industries, the demand for ultra-fine titanium alloy powders has increased significantly. It should be noted that the particle size of titanium alloy powders determines the application process. However, the high melting point of titanium and titanium alloys and the limitation of many factors, such as the prepared powders being easily contaminated by secondary pollution, make the preparation cost higher, which restricts their promotion and application. In this study, the research progress of micro and nano titanium alloy powder preparation process is described, and the existing problems of various processes are analyzed and discussed, and it is proposed that the direct reduction in TiO2 to obtain micro and nano titanium alloy powder is the key research direction in the future. In particular, the preparation of micro and nano titanium alloy powder by “calciothermic self-propagation process” has great industrial potential.

Abstract Production of liquid fertilizers containing nitrogenous nutrients and biostimulants from sewage sludge (SS-NB) has been attracting increasing attention due to its excellent fertilization effect and resource recycling attributes. To better understand the functional effects of nutrients and biostimulants in SS-NB on soil, the adsorption capacity and mechanism of straw biochar (SB) and wood chip biochar (WCB) for alkaline and neutral SS-NB components were investigated. The adsorption of total organic carbon (TOC) from alkaline and neutral SS-NB by WCB was 61.14% and 89.73%, respectively, higher than that by SB, which was 56.25% and 83.36%. Moreover, TOC from neutral SS-NB was more readily adsorbed, especially for fulvic and humic acids. SB had a strong adsorption capacity for calcium ions and nitrogen (TKN, nitrate N, protein, amino acid) and released large amounts of P. In addition, WCB and SB showed a strong affinity for macromolecules (proteins) and reducing substances (lignin and lipids) and excellent fixation ability for phytohormones and allelochemicals. However, WCB adsorbed more types of molecular substances than SB while maintaining a high immobilization rate. Analysis of the adsorption mechanism showed that surface amino groups of the biochar were involved in adsorption, while WCB had additionally high adsorption efficiencies through pore adsorption, hydrogen bonding adsorption and pore size-exclusion effects. The study revealed that biochar can be used as an efficient adsorption carrier for SS-NB to improve soil fertility management. Graphical Abstract

Abstract Background The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. Methods From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients’ demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. Findings In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). Interpretation In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.