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The global flood risk urges an improved understanding of flood magnitude and its mechanism, which needs insights from pre-instrumental flood investigations. Due to data scarcity, reconstructing pre-instrumental flood magnitudes relies on statistical downscaling, failing to capture nonlinear and dynamic characteristics. We developed a dynamical approach, NorESM-WRF-SWAT, integrating a global climate, a regional, and a hydrologic model to investigate the 1931 Yangtze River flood (the deadliest in the world) and compared it with the 1998's. Through validation, our method outperforms the statistical method in simulating precipitations and river discharges. For the first time, we presented detailed insights into the intensity and duration of the 1931 flood, revealing a smaller magnitude but associated with an amplified loss, likely due to social vulnerability and reduced societal resilience compared to the 1998's. While successful simulation can be interfered with by model variability, our dynamical method shows promise for simulating pre-instrumental flood and building a long-term pre-instrumental-hydrology database. [ABSTRACT FROM AUTHOR]

In practical supply chain operations, efficient order allocation significantly enhances the overall efficiency of the supply chain. Real production environments are plagued by numerous uncertainties, such as unpredictable customer orders, which greatly amplify the complexity of solving practical allocation problems. This study focuses on the problem of allocating orders to parallel machines with varying efficiencies under uncertain and high-dimensional conditions. To maximize the expected profit of order processing, a mathematical model for a high-dimensional stochastic optimization problem is developed, considering the uncertainty due to potential customer order cancellations in a real-world production. By integrating an intelligent optimization algorithm for the order assignment problem with a scenario generation approach, a novel framework for intelligent stochastic optimization is proposed. This framework employs an intelligent optimization algorithm suitable for the generalized assignment problem to search for improved solutions and utilizes the scenario generation method to produce the necessary scenarios for evaluating solutions in high-dimension. Experimental results demonstrate that the proposed approach effectively addresses the high-dimensional stochastic order allocation problem, outperforming the compared method in terms of efficiency and capability. [ABSTRACT FROM AUTHOR]

Histone demethylation in cardiac hypertrophy is poorly understood. This study aims to determine the role of the histone demethylase LSD1 in pathological cardiac hypertrophy. Both isoprenaline (ISO)-treated and transverse aortic constriction (TAC)-treated rats developed hypertrophic hearts. LSD1 was significantly decreased; the histone marks mono- and dimethyl H3K4 and H3K9 (H3K4me1/2 and H3K9me1/2) were significantly up-regulated in the hypertrophic heart tissue, as well as the expression of the ANP, α-HMC and MLV-2v genes. An LSD1 inhibitor, OG-L002 could also induce cardiac hypertrophy and enhance the induction of cardiac hypertrophy by ISO. Overexpressed LSD1 abolished ISO-induced cardiac hypertrophy and downregulated H3K4me1/2 and H3K9me1/2 expression. Overexpression of LSD1 also reduced the expression of ANP, α-HMC and MLV-2v. In addition, we have reported isoprenaline (ISO) as one of the histone demethylase LSD1 inhibitors. This was confirmed by molecular docking, molecular dynamic studies and a histone demethylation assay. The H3K4me1/2 expression increases with the incubation of ISO in HEK 293T and HELA cells. CaMKII could be significantly activated by the LSD1 inhibitor OG-L002 as well as by ISO in rats. In summary, we have identified a novel role for LSD1 in initiating and maintaining cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55 μg/mL to bare IMB to 359,967.62 ± 20,059.42 μg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage. [ABSTRACT FROM AUTHOR]

A Lawson-type exponential integrator combined with the Fourier pseudo-spectral method is provided for the nonlinear Double Sine-Gordon equation (DSGE), while the nonlinearity is characterized by β / ϵ with small parameter ϵ ∈ (0 , 1 ] and interaction parameter β ∈ (0 , + ∞) . In comparison to the Sine-Gordon equation, DSGE has many properties of solitons as well as its own unique new features. This is the first work to numerically simulate the physical phenomena arising from DSG kinks collisions. The improved uniform error bounds are proved by using the regularity compensation oscillatory (RCO) technique, which are O (α 2 τ + h m) up to the long time at T ϵ = T / α 2 , where α = ϵ for β ≥ 1 and α = ϵ / β for 0 < ϵ < β < 1 . Based on the uniform bounds, the error estimation for the discrete energy is derived. Furthermore, the improved error bounds are extended to two oscillatory DSGEs with O (ϵ 2) and O (ϵ 2 / β 2) wavelength in time. Numerical examples are provided to illustrate the accuracy and discrete energy property of the proposed method. [ABSTRACT FROM AUTHOR]

We couple together existing ideas, existing results, special structure and novel ideas to accomplish the exact limits and improved decay estimates with sharp rates for all order derivatives of the global weak solutions of the Cauchy problem for an n-dimensional incompressible Navier-Stokes equations. We also use the global smooth solution of the corresponding heat equation to approximate the global weak solutions of the incompressible Navier-Stokes equations. [ABSTRACT FROM AUTHOR]

TNBC, the most aggressive form of breast cancer, lacks accurate and effective therapeutic targets. Immunotherapy presents a promising approach for addressing TNBC. Anxiety and depression are frequently concurrent symptoms in TNBC patients. MDD affects the tumor immune microenvironment of TNBC, with its characteristic genes affecting the pathophysiology of MDD and potentially increasing the risk of TNBC recurrence and metastasis. This study reveals significant differences in T lymphocyte infiltration between high-risk and low-risk TNBC groups based on MDD feature genes. This finding aids in identifying TNBC patients who may benefit from immunotherapy, providing new insights for future TNBC immunotherapy strategies. Our aim is to identify MDD-related genes involved in the pathogenesis of TNBC and to provide predictive biomarkers for TNBC immunotherapy. [ABSTRACT FROM AUTHOR]

Single cell RNA sequencing has provided unprecedented insights into the molecular cues and cellular heterogeneity underlying human disease. However, the high costs and complexity of single cell methods remain a major obstacle for generating large-scale human cohorts. Here, we compare current state-of-the-art single cell multiplexing technologies, and provide a widely applicable demultiplexing method, SoupLadle, that enables simple, yet robust high-throughput multiplexing leveraging genetic variability of patients. Here the authors establish and benchmark a single cell RNA multiplexing framework that enables simple, yet robust high-throughput multiplexing leveraging single cell nucleotide polymorphisms of patients. [ABSTRACT FROM AUTHOR]

Background: Aberrant glycosylation is one of the hallmarks of cancer. The profile of glycoprotein expression caused by abnormal glycosylation has been revealed, while abnormal glycogenes that may disturb the structure of glycans have not yet been identified in esophageal squamous cell carcinoma (ESCC). Methods: Genomic alterations driven by differentially expressed glycogenes in ESCC were compared with matched normal tissues by multi-omics analysis. Immunohistochemistry, MTT, colony formation, transwell assays, subcutaneous tumor formation experiments and tail vein injection were used to study the expression and the effect on the proliferation and metastasis of the differentially expressed glycogenes POFUT1 and RPN1 in ESCC. In the alkyne fucose labeling experiment, AAL lectin affinity chromatography and immunoprecipitation were used to explore the mechanism of POFUT1 in ESCC. Results: The expression of the POFUT1 and RPN1 glycogenes were upregulated, as determined by genomic copy number gain and proteomics analysis. The overexpression of POFUT1 or RPN1 was associated with poor prognosis in ESCC patients and affected the proliferation and metastasis of ESCC in vivo and in vitro. The overexpression of POFUT1 increased the overall fucosylation level and activated the Notch signaling pathway, which partially mediated POFUT1 induced pro-migration in ESCC. The regulation of malignant progression of ESCC by RPN1 may be related to the TNF signaling pathway, p53 signaling pathway, etc. Conclusions: Our study fills a gap in the study of abnormal glycogenes and highlights the potential role of the POFUT1/Notch axis in ESCC. Moreover, our study identifies POFUT1 and RPN1 as promising anticancer targets in ESCC. [ABSTRACT FROM AUTHOR]

Industrial hemp (Cannabis sativa L.) is a multifaced crop that has the potential to be exploited for many industrial applications, and making use of salt lands is considered to be a sustainable development strategy for the hemp industry. However, no elite salt-tolerant hemp varieties have been developed, and therefore supplementing appropriate exogenous substances to saline soil is one possible solution. Calcium-containing compounds are well-known for their salt tolerance enhancing effects, but the underlying molecular mechanisms remain largely unclear. Here, we first assessed the ameliorative effects of calcium amendments on salt-stressed hemp plants and then investigated these mechanisms on hemp using integrative analysis of proteomics and metabolomics. The stress phenotypes could be lessened by Ca2+ treatment. Certain concentrations of Ca2+ maintained relative electrical conductivity and the contents of malondialdehyde and chlorophyll. Ca2+ treatment also generally led to greater accumulations of soluble proteins, soluble carbohydrates and proline, and enhanced the activities of superoxide dismutase and peroxidase. Through functional classification, pathway enrichment, and network analysis, our data reveal that accumulation of dipeptides is a prominent metabolic signature upon exogenous Ca2+ treatment, and that changes in mitochondrial properties may play an important role in enhancing the salt tolerance. Our results outline the complex metabolic alternations involved in calcium-mediated salt stress resistance, and these data and analyses would be useful for future functional studies.Key message: Integrated omics analyses outline cellular and metabolic processes underlying calcium-mediated salt tolerance in hemp and highlight the important roles of accumulation of dipeptides and changes in mitochondrial properties. [ABSTRACT FROM AUTHOR]

Aluminum (Al) exposure was implicated in neurodegenerative diseases and cognitive impairment, yet the involvement of zinc (Zn) and its mechanism in Al-induced mild cognitive impairment (MCI) remains poorly understood. The objective is to explore the role of Zn in Al-induced cognitive impairment and its potential mechanisms. Montreal cognitive assessment (MoCA) test scores and serum Al, Zn from Al industry workers were collected. A mediation analysis was performed to evaluate the role of serum Zn among serum Al and MoCA test scores. Subsequently, an Al-exposure study was conducted on a rat model categorized into control, low-, medium-, and high-dose groups. After a Morris Water Maze test and detection of Al, Zn content in the hippocampus, integrated transcriptomic and proteomic analyses between the control group and the high-dose group were performed to identify the differentially expressed genes (DEPs), proteins (DEPs), and pathways. To corroborate these findings, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) were selected to identify the gene and protein results. Zn overall mediates the relationship between serum Al and cognitive function (mediation effect 17.82%, effect value = − 0.0351). In the Al-exposed rat model, 734 DEGs, 18 miRNAs, 35 lncRNAs, 64 circRNAs, and 113 DEPs were identified between the high-dose group and the control group. Among them, ROCK1, DMD, and other four DEPs were identified as related to zinc finger proteins (ZNF). Co-enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) linked these changes to the RHOA/ROCK1 signaling axis. ZNF-related proteins Rock1, DMD, and DHX57 in the high-dose group were downregulated (p = 0.006, 0.003, 0.04), and the expression of Myl9, Rhoa, miR431, and miR182 was also downregulated (p = 0.003, 0.032, 0.032, and 0.046). These findings also show correlations between Al, Zn levels in the hippocampus, water maze performance, and expressions of Myl9, Rhoa, miR431, miR182, DMD, ROCK1, and DHX57, with both negative and positive associations. Based on the results, we determined that Zn was involved in Al-induced MCI in Al workers and Al-exposed rat models. Al exposure and interaction with Zn could trigger the downregulation of ZNF of ROCK1, DMD, and DHX57. miR431, miR182 regulate RHOA/ROCK1 was one of the Zn-involved pathways in Al-induced cognitive impairment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of dietary metformin supplementation on the redox balance, inflammation, mitochondrial biogenesis, and function in blunt snout bream fed a high-carbohydrate (HC) diet. Fish (45.12 ± 0.36 g) were randomly offered four diets, including a control diet (33% carbohydrate), an HC diet (45% carbohydrate), and the HC diet supplemented with 0.06% (HCM1) and 0.12% (HCM2) metformin respectively for 12 weeks. Compared with the control, feeding the HC diet significantly increased the hepatosomatic index (HSI), the mesenteric fat index, liver and muscle glycogen contents, liver and adipose tissue lipid contents, plasma glucose and glycation end products (AGES) levels and aspartate transaminase activity, plasma and liver malondialdehyde (MDA) contents, hepatic adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents, mitochondrial cytochrome c content, mitochondrial complex IV activity and ATP 6 transcription, but decreased plasma catalase (CAT) activity, muscle superoxide dismutase (SOD) activity, hepatic antioxidant enzymes activities, and the transcriptions of transforming growth factor β (tgfβ) and interleukin 10 (il10). Compared with the HC group, metformin treatment (especially the HCM2 group) significantly elevated tissue glycogen contents, muscle SOD activity, plasma and liver antioxidant enzymes activities, the transcriptions of tgfβ and il10, the sodium/potassium ATPase activity, the contents of mitochondrial protein and AMP, the level of p-AMP activated protein kinase (AMPK), and the p-AMPK/t-AMPK ratio, but lowered the HSI, tissue lipid contents, plasma levels of glucose, AGES and glycated serum protein, plasma, and liver MDA contents, the transcriptions of il1β, NADH dehydrogenase subunit 1 and ATP 6, the contents of ATP and cytochrome c, the ATP/AMP ratio, and the activities of complexes I and IV. In conclusion, metformin could attenuate the HC diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in blunt snout bream. [ABSTRACT FROM AUTHOR]

Depression among adolescents is a significant concern both in China and globally. While previous research has acknowledged the influence of family life on adolescent depression, there has been limited exploration of housework, a key aspect of family dynamics. Using data from the China Family Panel Studies (CFPS) spanning 2016–2020, this study investigates the relationship between household chores and adolescent depression. The sample comprises 977 students with data collected over three waves. Our findings reveal a positive association between the duration of housework (DHT) and adolescent depression. Specifically, controlling for other factors, each additional hour of housework corresponds to a 0.38 increase in the CESD-20 score, indicating heightened depression levels. Additionally, the study highlights that the impact of DHT on depression is most pronounced among rural Chinese adolescents, particularly rural Chinese girls. This trend may be linked to prevailing son preference in rural Chinese communities. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative gastroparesis occurs after surgeries which affect the upper digestive tract. Gastric peroral endoscopic myotomy (G-POEM) is a treatment for postoperative gastroparesis. The present study boasts the long-term efficacy and safety of G-POEM in a large cohort of patients. Patients and methods: Gastroparesis Cardinal Symptom Index (GCSI) and Gastroesophageal Reflux Disease Questionnaire (GERDQ) were utilized for the assessment of postsurgical gastroparesis symptoms. Gastroscope was used to observe the anastomotic site. Three-dimensional ultrasound was used to measure the morphological structure of the gastric antrum and pylorus tube. Gastric emptying time was calculated by analyzing the volume change of gastric antrum. Results: Significant clinical effectiveness of G-POEM was observed. The GCSI score, including each subscale score, showed significant decrease after G-POEM. Before G-POEM, there was a negative correlation between GCSI score and the inner diameter of pylorus, as well as a positive correlation with the length of pyloric tube. The similar results were found in the scores of nausea/vomiting and postprandial fullness/early satiety subscales. No correlation was observed between GCSI score and the emptying time, nor between the emptying time and the parameters of antrum morphology. After G-POEM, no correlation was found between GCSI (including subscales) score, the emptying time, and the parameters of antrum morphology. Patients who exhibited as clinical non-responders often accompanied with GERD symptoms. After G-POEM, the score of GERDQ decreased significantly. Either before or after G-POEM, no correlation was noticed between GERDQ scores, the emptying time and the parameters of antrum morphology. Conclusion: The technique of G-POEM was demonstrated as a minimally invasive approach with the long-term efficacy and safety in therapying postoperative gastroparesis. [ABSTRACT FROM AUTHOR]

Three-metal-core-shell nanoparticles (Au@Pt@PdNPs) providing excellent peroxidase-like activity were applied in lateral flow immunoassay (LFIA), designated as Au@Pt@Pd-LFIA, for detecting the nucleocapsid protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An Au@Pt@Pd-LFIA was developed for quantitatively testing of SARS-CoV-2 NP with a range 0.12–31.25 ng/mL. The limit of detection (LOD) of Au@Pt@Pd-LFIA strip was 0.06 ng/mL, which was 16-fold or eightfold more sensitive than that of the gold lateral flow immunoassay (Au-LFIA) and the gold flower flow immunoassay (AF-LFIA) strips, respectively. For detection of clinical samples from nasal swabs using test strips, Au@Pt@Pd-LFIA had 84.09% sensitivity, 100% specificity, and 92.55% accuracy. In terms of detection time, the testing of Au@Pt@Pd-LFIA strip was 16 min similar to Au-LFIA (15 min) and AF-LFIA (10 min), but much shorter than ELISA (2 h). In conclusion, Au@Pt@Pd-LFIA is a sensitive, rapid, and simple test for quantitative detection of SARS-CoV-2 NP in nasal swab samples. [ABSTRACT FROM AUTHOR]

Background: Handgrip strength (HGS) weakness and asymmetry are both abnormal conditions of upper-limb muscle strength. The association between HGS weakness and physical performance is controversial, and the link between HGS asymmetry and physical performance remains unclear. Aims: This study aimed to investigate the associations of HGS weakness and asymmetry separately and concurrently with low physical performance among Chinese older people. Methods: The study used two waves of data from China Health and Retirement Longitudinal Study (CHARLS) in 2013 and 2015. HGS weakness and asymmetry were defined according to the maximal HGS and the HGS ratio, respectively. Participants were classified into 4 groups according to HGS status: normal, asymmetry only, weakness only, and concurrent weakness and asymmetry. The logistic regression model was used to investigate the cross-sectional association between low physical performance and each of maximal HGS, HGS ratio, and HGS status, as well as the prospective association between baseline HGS status and new-onset physical performance decline after two years. Results: Participants with HGS asymmetry only, weakness only, and two abnormalities showed a higher prevalence of low physical performance when asymmetry defined as an HGS ratio exceeding 1.20 and 1.30 (all, p < 0.001), with the greatest odds in those with two abnormalities (20% threshold: OR 3.83; 30% threshold: OR 5.41). The longitudinal analysis found that HGS weakness can predict the new-onset low physical performance over a two-year period, with concurrent HGS asymmetry further increased the future risk of physical performance decline. Conclusions: Both HGS weakness and asymmetry were associated with a higher prevalence of low physical performance, in an additive way. This study will help screen older people with low physical performance more efficiently, and identify those at higher risk of developing new-onset physical performance decline within two years. [ABSTRACT FROM AUTHOR]

The goal of this article was to analyze the microstructural, texture development, deformation mode, and mechanical properties of a Mg–8.7Gd–4.18Y–0.42Zr (wt%) magnesium alloy that underwent conventional extrusion in conjunction with equal channel angular pressing (EX-ECAP) deformation. The findings indicate that as-extruded alloy reveals a significant basal texture, while the ECAPed GW94K alloy demonstrates basal poles that are inclined ~ 45° from the extrusion direction. After 4p-ECAP process at 370 °C via the Bc path, the microstructure of the alloy exhibits a high level of uniformity, with a fine grain area fraction of 92.7% and an average grain size of 3 μm. The GW94K alloy experiences a significant increase in elongation when the ECAP pass is increased, although the ultimate tensile strength (UTS) decreases remarkably. In particular, the sample subjected to ECAP demonstrates a room-temperature tensile elongation of 36.8% in the extrusion direction. This phenomenon can be ascribed primarily to the evolution of the texture during repeated ECAP processes, leading to the activation of multiple deformation modes in ECAP deformation process of the GW94K alloy. Furthermore, the results suggest that the presence of multiple slip systems, characterized by their high Schmid factor and IGMA analyses, significantly influences the uniform elongation. [ABSTRACT FROM AUTHOR]

Background: Patients with Crohn's disease (CD) experience disease progression over time, including strictures/stenoses, penetrating fistulae, and abscesses. Aims: This retrospective US population-based study aimed to characterize CD progression in newly diagnosed patients. Methods: Patient-level data from the Optum® Market Clarity database from January 1, 2016, to June 30, 2020, were used. The study comprised a 12-month baseline period (pre-diagnosis), an index date (diagnosis date), and a follow-up period. The risk of, and time to, CD progression since CD diagnosis, dispensed treatment changes following CD progression, and healthcare resource utilization before and after CD progression were assessed. Results: Overall, 6804 newly diagnosed patients were included. Of these, 1714 (25.2%) experienced CD progression as follows: 19.3% (1183/6117) in the first 6 months, 21.6% (1188/5503) by 1 year, 24.6% (953/3875) by 2 years, and 26.6% (444/1668) by 3 years. Intestinal obstruction/stenosis was more common than fistula or abscess. Among patients with CD progression, the median (interquartile range) estimated time to progression was 2 (0–140) days; the shortest time to progression was seen with a first intestinal obstruction/stenosis (0 [0–137] days). The frequency of several dispensed treatments increased following CD progression. Among patients who experienced progression, CD-related inpatient hospital admissions/visits increased from 436 of 1714 patients (25.4%) in the month before progression to 965 (56.3%) in the month after progression. Conclusions: Over one quarter of patients with newly diagnosed CD experienced CD progression and complications within 3 years of diagnosis, highlighting the importance of monitoring for progression and early intervention to limit progression. [ABSTRACT FROM AUTHOR]

Crossing departmental boundaries and improving the efficiency of policy instruments are potential solutions to break the dilemma of public affairs governance and shift to collaborative governance. It is necessary to re-examine the internal connection mechanism between intergovernmental relations and policy tools. This study used textual analysis to deconstruct 178 water pollution control policies from 1984 to 2020, provided an overview of 16 control sectors and 30 policy instruments; then used social network analysis to characterize the structure of the water pollution control network, discussed the principles of reciprocity and priority of cross-sector cooperation, the shift in preference in the choice of policy instruments, and the institutional logic of the "sector-instrument" interface. First, the network characteristics of the governance body evolves from "one-core multiple" to "multiple synergy." The means of the degree, closeness and betweenness centrality of the current policy stage are 0.79, 0.85, and 0.04, respectively. Second, the selective preference of policy instruments will shift from command-and-control preference to a balanced choice of multiple policy instruments. The mean values of degree, closeness and betweenness centrality in the current policy stage are 0.79, 0.92, and 0.01, respectively. Thirdly, the sectoral collaboration and policy instruments both follow the "relationship-interaction-synergy" process in the evolution of policy elements. The structural characteristics of the network change from "loose" in the policy construction stage to "decentralized-coupled" in the policy innovation stage to "core-edge" in the institutional innovation stage, and the current the network density is 69.14 and the connection degree is 0.93. This study enriches the knowledge of water pollution governance policy design and policy implementation, and provides ideas to consider the relationship between governance sectors and the embeddedness of instruments. [ABSTRACT FROM AUTHOR]

The tight sandstone reservoris are important exploration and production target in the Xujiahe Formation in Xinchang area of Western Sichuan. Due to the various lithofacies and diagenetic alteration in distributary channel belt sandstones, the reservoirs exhibit strong heterogeneity. The strong heterogeneity makes the identification of petrologically superior sandbodies a great challenge. In order to better understand reservoir quality, this study constructs a model between diagenetic alterations and reservoir quality within distributary channel belts. 73 plug samples were taken from 17 wells located in the channel belt. An integration of thin sections, X-ray diffraction, carbon and oxygen isotope ratios, cathodoluminescence, and micro-CT were analysed for the genesis and distribution of reservoir quality. The results show that subaqueous distributary channels are formed under various hydrodynamics, resulting in different lithofacies. The thicknesses of channels can be divided into less than 2 m, 2–6 m, and more than 6 m. The diagenetic alteration in lithofacies were identified. Coarse-grained sandstones with low content of rock fragments are relatively weakly compacted with less calcite and chlorite cementation. Fine-grained sandstones with high content of rock fragments are strongly compacted with calcite cementation during early diagenesis. The dissolution pores are related to the soluble mineral content and the distribution of mudstones. The subaqueous distributary channels formed in high-energy, moderate-energy, and low-energy hydrodynamic settings have experienced different diagenetic intensities. Additionally, fractures can effectively improve the reservoir properties. The distribution of good quality reservoirs is controlled by the combined influence of diagenetic heterogeneity and fractures. This would help to promote better understanding of reservoir quality within the subaqueous distributary channel belts in braided-river delta front. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma. Methods: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line). Group D was the only group in which participants received the study treatment in the first-line setting. The primary endpoint was safety. Results: Following previous report on groups A and B, results of group D are herein presented. As of February 7, 2023, 61 patients were enrolled and were followed up for a median of 25.5 months. Grade ≥ 3 treatment-emergent adverse events were reported by 29 (47.5%) patients. One patient died from adverse events that were considered related to study treatment. Among the patients with at least one post-baseline tumor assessment (n = 58), the objective response rate was 29.3% (95% CI: 18.1–42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. IRRC-assessed median progression-free survival was 7.3 months (95% CI: 2.8–11.0), and median overall survival was 20.4 months (95% CI: 15.0–NE), respectively. Conclusion: Serplulimab combination therapy with HLX04 showed a manageable safety profile as well as preliminary efficacy in patients with advanced HCC in the first-line setting. [ABSTRACT FROM AUTHOR]

A high cell-surface hydrophobic bacterium, strain A18T, was isolated from a waste digestion system in Chaozhou, China. Cells of strain A18T were Gram-stain-positive, aerobic, non-spore-forming, non-motile, and rod-shaped. Phylogenetic analyses based on the 16S rRNA gene showed that strain A18T shared less than 94.2% sequence similarity to all validated species in the family Chitinophagaceae, and formed a distinct lineage close to genera Niabella and Terrimonas in the neighbor-joining tree, indicating that strain A18T is a novel species. Genome-based phylogenetic analyses revealed that strain A18T is affiliated to the genus Niabella. The cellular components, including iso-C15:0 and iso-C15:1 G as the major fatty acids, menaquinone-7 as the respiratory quinone and a DNA G + C content of 40.54% supported strain A18T as a member of the genus Niabella. However, the physiological and biochemical properties, such as enzyme activities, carbon source utilization and C18:0 3-OH as another major fatty acids, distinguished strain A18T from its close related species. Therefore, the name Niabella digestorum sp. nov. is proposed for this novel species. The type strain is A18T (= GDMCC 1.3242 T = KCTC 92386 T). [ABSTRACT FROM AUTHOR]

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09–1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09–1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04–1.68). A positive global genetic correlation was observed (cIMTmax-AS: =0.23, P=9.44 × 10−5; cIMTmean-AS: =0.21, P=3.00 × 10−4; cIMTmin-AS: =0.16, P=6.30 × 10−3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97–1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93–1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90–1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01–0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01–0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01–0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited. [ABSTRACT FROM AUTHOR]

In this paper, we design the differentially private variants of the classical Frank-Wolfe algorithm with shuffle model in the optimization of machine learning. Under weak assumptions and the generalized linear loss (GLL) structure, we propose a noisy Frank-Wolfe with shuffle model algorithm (NoisyFWS) and a noisy variance-reduced Frank-Wolfe with the shuffle model algorithm (NoisyVRFWS) by adding calibrated laplace noise under shuffling scheme in the ℓp(p ∈ [1, 2])-case, and study their privacy as well as utility guarantees for the Hölder smoothness GLL. In particular, the privacy guarantees are mainly achieved by using advanced composition and privacy amplification by shuffling. The utility bounds of the NoisyFWS and NoisyVRFWS are analyzed and obtained the optimal excess population risks O (n − 1 + α 4 α + log (d) log (1 / δ) n ϵ) and O (n − 1 + α 4 α + log (d) log (1 / δ) n 2 ϵ) with gradient complexity O (n − (1 + α) 2 4 α 2 ) for α ∈ [ 1 / 3 , 1 ] . It turns out that the risk rates under shuffling scheme are a nearly-dimension independent rate, which is consistent with the previous work in some cases. In addition, there is a vital tradeoff between (α, L)-Hölder smoothness GLL and the gradient complexity. The linear gradient complexity O (n) is showed by the parameter α = 1. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of poor sleep quality (PSQ) in the general population leads to negative health outcomes. Since estimates of PSQ prevalence in the Chinese general population vary widely, this meta-analysis aimed to refine these estimates and to identify moderating factors. Methods: A comprehensive literature search was undertaken in both international (PubMed, PsycINFO, Web of Science, and EMBASE) and Chinese (Wanfang, and the China National Knowledge Infrastructure databases) databases from inception to 23 November 2023. Studies were required to have used standard scales such as the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). The pooled prevalence of PSQ and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify sources of heterogeneity. Results: In 32 studies with a combined 376,824 participants, the pooled prevalence of PSQ was 19.0% (95% CI 15.8–22.8%; range 6.6–43.6%). Across 22 studies that reported PSQI data, the pooled mean score was 4.32 (95%CI 3.82–4.81; SD = 0.502). The pooled mean sleep duration across 8 studies was 7.62 (95% CI 7.23–8.00; SD = 0.194) hours. Subgroup analyses showed that lower education (Q = 4.12, P = 0.042), living in less developed regions (Q = 60.28, P < 0.001), and lower PSQI cutoff values (Q = 9.80, P = 0.007) were significantly associated with PSQ. Meta-regression analyses showed that study quality was inversely associated with estimated PSQ prevalence (β = − 0.442, P = 0.004). Limitations: Although measures such as subgroup and meta-regression analyses were performed, substantial heterogeneity remained. Information related to sleep quality, such as comorbid physical diseases or psychiatric disorders, substance use, occupational types, and employment status, were not reported in most studies. Conclusion: One in five people in the general population of China may have PSQ and people with lower education or living in western regions may be more susceptible. [ABSTRACT FROM AUTHOR]

High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway. [ABSTRACT FROM AUTHOR]

Mathematical problem posing, generally defined as the process of interpreting given situations and formulating meaningful mathematical problems, is academically important, and thus several interventions have been used to enhance this competence among students and teachers. Yet little is known about the interventions' various components and their relative or combined effectiveness. In this meta-analysis of 26 intervention studies in mathematics, we identified nine intervention components and found that the interventions had a medium, positive, and significant mean weighted effect size. A stepwise meta-regression analysis revealed that intervention efficacy varied by moderators relevant to the research design, sample characteristics, and intervention characteristics. The findings obtained from this meta-analysis are expected to serve as a foundation for future efforts to design and implement (more) effective interventions to improve mathematical problem posing competence. [ABSTRACT FROM AUTHOR]

Phosphorus modification is a prevalent technique for enhancing the hydrothermal stability and adjusting the acidity of zeolite catalysts. The relation between the structure of phosphorus-modified zeolite catalysts and their catalytic performance has been studied using ZSM-5 zeolites. However, phosphorus modification of ZSM-5 zeolites is usually performed after template removal via calcination, and the phosphorus modification of ZSM-5 zeolites without template removal has not been comprehensively studied. This study comparatively examines the phosphorus modification of ZSM-5 before and after template removal during aromatization of 1-octene. The structures of both catalyst samples (with and without template removal) were characterized via X-ray diffraction, nuclear magnetic resonance spectroscopy, infrared spectroscopy, and temperature-programmed desorption of ammonia and correlated with their catalytic performance. Results indicate that phosphorus modified ZSM-5 zeolites without template removal exhibit superior catalytic activity to those with template preremoval in the aromatization of 1-octene and hydrothermal treatment. The stabilizing effect of the template on phosphorus-modified ZSM-5 zeolites during the aromatization reaction and hydrothermal treatment is discussed based on comprehensive characterization of both the P-modified ZSM-5 catalysts. This study elucidates the influence of the template on P-modified zeolite catalysts and offers a new reference for the post-treatment of zeolites. [ABSTRACT FROM AUTHOR]

Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis. [ABSTRACT FROM AUTHOR]

Background: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people's quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity. Aims: However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear. Methods: We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA. Results: We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1. Conclusions: Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity. [ABSTRACT FROM AUTHOR]

This study delved into the acoustic spectrum of bubble clusters, each consisting of 352 vapor bubbles across volume fractions ranging from 0.005% to 40%. The clusters, organized in five distinct layers, were modeled using the volume of fluid (VOF) method to capture the bubble interfaces, and the Ffowcs Williams-Hawkings (FW-H) methodology to compute the far-field acoustic pressure from bubble collapse. Further analysis revealed distinct sound pressure behaviors across different volume fractions: For 25%–40%, time-domain analysis shows that the peak acoustic pressure pulses from the two innermost layers of bubbles are significantly higher than those from the outer layers. In the frequency domain, the octave decay rate of the acoustic pressure levels is relatively low, around −3dB/octave. For 0.5%–25%, four acoustic pressure pulses with similar widths and peak values were observed in the time domain. In the frequency domain, there are three distinct peaks in sound pressure levels (SPL), directly linked to the difference in collapse times of bubbles within the cluster, and the octave decay rate accelerates as the volume fraction decreases, stabilizing at −6dB/octave when the volume fraction is reduced to 17.5%. For 0.005%–0.5%, as the volume fraction decreases from 0.5% to 0.1%, the number of acoustic pressure pulses significantly reduces. Below 0.1% volume fraction, only a single wider pulse is observed. In the frequency domain, the octave decay rate gradually increases with decreasing volume fraction, significantly exceeding −10dB/octave when it drops below 0.1%, reaching up to −11.7dB/octave. [ABSTRACT FROM AUTHOR]

Visual and pressurized pipeline systems with single- and multi-undulation layouts were used to study experimentally and analyze theoretically the transient characteristics of water-air two-phase flow during water fillings in undulation pipelines based on the combination action analyses of both the communicating pipe and the gravity of the water-air two-phase flows in the descending pipe. For the single undulation pipeline, the complex two-phase flow-pattern evolutions including full pipe flow and stratified flow for low, medium, high water-filling velocity cases, respectively, lead to a great difference in transient pressure, flow pattern and the water-filling duration. Especially for low and medium water-filling velocity cases, the hydraulic theories related to hydraulic drop and hydraulic jump were employed to investigate the entrapped air pocket evolutions in the descending pipe, and the mechanism of negative pressure at the top of the undulation pipes was analyzed. For the same multi-undulation pipeline, due to the different elevations of the three undulation points along flow direction, namely three different types of pipeline layout, high-medium-low case (high elevation undulation point, medium one, and low one), low-medium-high and high-low-medium ones, their water-filling durations are significantly different, i.e., approximately 80.02 s, 227.34 s and 617.78 s. Meanwhile, there are significant differences in flow patterns in water filling, namely larger entrapped air pockets in three descending pipes for the high-medium-low case, entrapped air pockets in the first two descending pipes and open channel stratified flow in the last one for low-medium-high case, some bubbles in three descending pipes for the high-low-medium case. [ABSTRACT FROM AUTHOR]

Ovarian aging reduced the quality of oocytes, resulting in age-related female infertility. It is reported that mesenchymal stem cells (MSCs) therapy can improve age-related ovarian function decline and the success rate of in vitro maturation (IVM) in assisted reproductive therapy. In order to investigate the effectiveness and mechanisms of MSCs to enhance oocyte quality of cumulus oocyte complexes (COCs) in advanced age, this study focus on the respective functional improvement of oocytes and granulosa cells (GCs) from aging mice and further to explore and verify the possible mechanisms. Here, we studied a popular but significant protein of follicular development, Forkhead box O-3a (FOXO3a), which is a transcription factor that mediates a variety of cellular processes, but the functions of which in regulating oocyte quality in MSCs therapy still remain inconclusive. In this study, the RNA-seq data of metaphase II (MII) oocytes and GCs isolated from COCs confirmed that, GCs of immature follicles show the most potential to be the targeted cells of bone marrow mesenchymal stem cells (BMSCs) by FOXO3a signaling pathway. Furthermore, we demonstrated the effectiveness of BMSCs co-culture with aging COCs to enhance oocyte quality and found its mechanism to function via ameliorating the biological function of GCs by alleviating FOXO3a levels. These results provide significant fundamental research on MSCs therapy on ovarian aging, as well as offering guidance for raising the success rate of assisted reproductive technology such IVM in clinical and non-clinical settings. [ABSTRACT FROM AUTHOR]

The emergence of 3D Gaussian splatting (3DGS) has greatly accelerated rendering in novel view synthesis. Unlike neural implicit representations like neural radiance fields (NeRFs) that represent a 3D scene with position and viewpoint-conditioned neural networks, 3D Gaussian splatting utilizes a set of Gaussian ellipsoids to model the scene so that efficient rendering can be accomplished by rasterizing Gaussian ellipsoids into images. Apart from fast rendering, the explicit representation of 3D Gaussian splatting also facilitates downstream tasks like dynamic reconstruction, geometry editing, and physical simulation. Considering the rapid changes and growing number of works in this field, we present a literature review of recent 3D Gaussian splatting methods, which can be roughly classified by functionality into 3D reconstruction, 3D editing, and other downstream applications. Traditional point-based rendering methods and the rendering formulation of 3D Gaussian splatting are also covered to aid understanding of this technique. This survey aims to help beginners to quickly get started in this field and to provide experienced researchers with a comprehensive overview, aiming to stimulate future development of the 3D Gaussian splatting representation. [ABSTRACT FROM AUTHOR]

Ground vibration is a crucial foundation for the study of blasting demolition and rock-soil failure. In this paper, a soil-layer coupling model is established using the discrete element method (PFC3D), which takes distribution of microscale features into account. Subsequently, based on the Mindlin solution in an elastic half-space subjected to concentrated forces, the difference between the theoretical and numerical solutions is validated, and this study further investigates the laws on impacting vibration responses. The results reveal that, under the impact action of falling hammer, the vibration velocity of soil particle approximates a triangular function over time. The vertical stress exhibits a distribution pattern of increasing initially with soil depth and then decreasing. The contact force chains disperse in a 'root-like' manner, leading to a tendency for shear failure in the soil. Actually, impact vibration is a process of accelerated energy conversion, with the majority of impact energy dissipated by various forms of damping. This method can provide a theoretical basis for the stability analysis of ground vibration and disaster prediction. [ABSTRACT FROM AUTHOR]

Background and aims: Increased nitrogen (N) deposition may exacerbate soil phosphorus (P) deficiency, which alters soil greenhouse gas (GHG) emissions by changing soil properties and understory vegetation in subtropical forests. However, the effects of N addition, P addition, and understory vegetation interactions on soil carbon dioxide (CO2) and nitrous oxide (N2O) emissions in forest ecosystems and their underlying mechanisms remain unclear. Methods: We conducted a continuous N and P addition experiment in a subtropical Chinese fir plantation. The effects of N and P addition on soil CO2 and N2O emissions with different understory vegetation were examined using a structural equation model. Results: The addition of N and P did not directly affect soil CO2 emission of the understory, which was affected by understory species (F = 2.86; p = 0.05). N indirectly and positively affects soil CO2 emission through plant elements, and directly affect N2O emission of understory soil. Compared with CK, the addition of N2 promoted the N2O cumulative emission by 74.3%. N has a direct positive effect on soil N2O emissions, while P addition indirectly exerts a negative influence on N2O emissions through its impact on soil properties. Plant elements and soil properties were explained in 26.3% of soil CO2 emissions, of which 17.6% and 16.0% variations were explained by plant elements and soil properties, respectively. Leaf total N was the most important factor for predicting CO2 emissions. Conclusions: Our results suggested that soil CO2 emission was more dependent on plant elements, and soil N2O emission was directly dependent on N addition rather than plant elements. Thus, different patterns of soil GHG emissions and associated controls following N and P addition provided novel insights into predicting the effects of understory vegetation on climate change mitigation outcomes. [ABSTRACT FROM AUTHOR]

Aims: Nitrous oxide (N2O) plays an important role in global climate change. Plant expansion can alter soil nutrient cycling and greenhouse gas (GHG) fluxes but the effects of fine root litter mixing from plant expansion on litter decomposition, nutrient cycling, and GHG fluxes are poorly understood. Methods: To evaluate the impacts of fine root litter mixing from plant expansion on GHG budgets, we conducted an in situ study over sixteen months in Japanese cedar (Cryptomeria japonica) plantations experiencing moso bamboo (Phyllostachys edulis) expansions. Litter decomposition and N2O production were quantified in a full-factorial complete-randomized design by comparing fine root litter of Japanese cedar, moso bamboo or their mixtures, with or without nitrogen (N) addition. Results: We found that litter mixing accelerated decomposition, demonstrating a synergistic non-additive effect (19% increase in mass loss). This might have accelerated release of chemicals that inhibit microbial activities because litter mixtures had lower microbial biomass. Soil N2O emissions in the mixed litter treatment were 16.8% and 24.4% lower than those with only cedar or bamboo litter, respectively. N deposition promoted mass loss of mixed litter (28% increase in mass loss) and increased N2O emissions by 36.7%, 60.6% and 33.6% from cedar, mixed and bamboo litter treatments, respectively. Conclusion: The expansion of moso bamboo promotes the return of soil nutrients, reduces N2O emissions, and potentially mitigates GHG emissions. However, with increasing N deposition in the future, moso bamboo expansion will likely contribute to global warming. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs. [ABSTRACT FROM AUTHOR]

Conclusions: The developed Chang'E 7 LSWMA prototype demonstrates high precision in measuring water content and isotope values, which are the most important part of the measurement process, and the experimental results offer valuable guidance for in-situ measurement and data inversion. The LSWMA will perform the measurements after obtaining drilling (up to 1 m deep) or surface samples on the Moon. The estimated water content has also been affected by the processes of sampling, transportation and heating in addition to TDLAS. Therefore, the overall errors need to be analyzed and corrected. For isotopes measurement, the repetitions of experiments on the Moon's PSR are limited due to power and temperature constraints. The memory effect error correction algorithm should be introduced to improve accuracy. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Levels of Evidence The purpose of this study was to evaluate the femoral tunnel position using a modified anatomic transtibial (TT) double‐bundle anterior cruciate ligament reconstruction (DBACLR) and to investigate the knee kinematics, graft length and graft bending angle following DBACLR.Ten patients who underwent DBACLR using the modified TT technique were included in the study. All patients performed a single‐legged lunge under a dual fluoroscopic imaging system to assess the 6 degrees of freedom tibiofemoral kinematics. Femoral tunnel position was evaluated via postoperative three‐dimensional (3D) computed tomography. The area centroids of anteromedial (AM) and posterolateral (PL) bundles were determined on 3D knee models. The lengths of AM and PL bundles, as well as graft bending angle at the femoral tunnel aperture, were measured by created virtual fibres.The reconstructed knee rotated more externally compared with the contralateral knee between 0° and 60° (p ≤ 0.049). There is no significant difference in the length change of AM bundle (n.s.) and PL bundle (n.s.) between the two sides from 0° to 120° during the lunge motion. The maximum graft bending angle at the femoral tunnel aperture occurred at 0° of knee flexion, with the AM graft bending angle was 72.6° ± 9.0° and the PL graft bending angle was 90.3° ± 9.7°.The modified TT technique used in this study could achieve anatomical ACL reconstruction, restoring graft length change patterns compared to contralateral knees. However, residual rotational instability of the reconstructed knee was observed after DBACLR, despite achieving anatomic tunnel placement. Therefore, double‐bundle reconstruction may not sufficiently address the persistent rotational instability of the knee. Additionally, larger graft bending angles at the femoral tunnel aperture were found with the modified TT technique. Therefore, further improvement to the TT technique should focus on reducing the graft's curvature while maintaining the anatomical properties of the knee joint. The findings of this study highlight the need for improved surgical techniques to address residual rotational instability and optimise graft curvature. These improvements are crucial for enhancing patient outcomes and long‐term joint function following ACL reconstruction.Level II. [ABSTRACT FROM AUTHOR]

Light serves as a crucial external zeitgeber for maintaining and restoring physiological homeostasis in most organisms. Disrupting of light rhythms often leads to abnormal immune function, characterized by excessive inflammatory responses. However, the underlying regulatory mechanisms behind this phenomenon remain unclear. To address this concern, we use in vivo imaging to establish inflammation models in zebrafish, allowing us to investigate the effects and underlying mechanisms of light disruption on neutrophil recruitment. Our findings reveal that under sustained light conditions (LL), neutrophil recruitment in response to caudal fin injury and otic vesicle inflammation is significantly increased. This is accompanied by elevated levels of histone (H3K18) lactylation and reactive oxygen species (ROS) content. Through ChIP-sequencing and ChIP‒qPCR analysis, we discover that H3K18 lactylation regulates the transcriptional activation of the duox gene, leading to ROS production. In turn, ROS further promote H3K18 lactylation, forming a positive feedback loop. This loop, driven by H3K18 lactylation-ROS, ultimately results in the over recruitment of neutrophils to inflammatory sites in LL conditions. Collectively, our study provides evidence of a mutual loop between histone lactylation and ROS, exacerbating neutrophil recruitment in light disorder conditions, emphasizing the significance of maintaining a proper light-dark cycle to optimize immune function. Through ChIP-sequencing and ChIP‒qPCR analysis, authors discover a positive feedback loop between histone lactylation and reactive oxygen species which exacerbates neutrophil recruitment under light disorder conditions in Zebrafish. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is an essential micronutrient but can be cytotoxic when present in excess. Plants have evolved mechanisms to tolerate Zn toxicity. To identify genetic loci responsible for natural variation of plant tolerance to Zn toxicity, we conduct genome-wide association studies for root growth responses to high Zn and identify 21 significant associated loci. Among these loci, we identify Trichome Birefringence (TBR) allelic variation determining root growth variation in high Zn conditions. Natural alleles of TBR determine TBR transcript and protein levels which affect pectin methylesterification in root cell walls. Together with previously published data showing that pectin methylesterification increase goes along with decreased Zn binding to cell walls in TBR mutants, our findings lead to a model in which TBR allelic variation enables Zn tolerance through modulating root cell wall pectin methylesterification. The role of TBR in Zn tolerance is conserved across dicot and monocot plant species. Zinc is an essential micronutrient for plants, however its excess causes cellular damage. Here, the authors report that natural variation of Trichome Birefringence (TBR) gene confers zinc toxicity tolerance through modulating root cell wall pectin methylesterification in Arabidopsis. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson's staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P < 0.05). Conversely, in the HG + inhibitor group, the protein expression of Collagen I and FN was notably reduced compared to the HG group (P < 0.05). The dual luciferase reporter assay confirmed that miR-483-3p could inhibit the luciferase activity of IGF-1's 3′-UTR region (P < 0.05). miR-483-3p exerts targeted regulation on IGF-1, promoting apoptosis and fibrosis in renal tubular epithelial cells induced by high glucose conditions. [ABSTRACT FROM AUTHOR]

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia–reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression. [ABSTRACT FROM AUTHOR]