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Abstract Background Sanniang Bay (SNB) and Dafeng River (DFR), located in the northern Beibu Gulf, is well-known as one of the eight habitats for humpback dolphins in China. This region is representative of typical estuarine and bay ecosystems and produce complex hydrodynamic seawater conditions. Moreover, anthropogenic pressure, such as eutrophication and large-scale infrastructure projects, have caused ongoing habitat deterioration and loss. It is urgent to know the phytoplankton community and their relationships with environmental factors in this region. Results In this study, we assessed the diversity and assembly mechanisms of phytoplankton communities, as well as their relationship with the physicochemical characteristics of seawater in SNB and DFR region using 18 S rDNA metabarcoding analysis. The results showed that seasonal changes markedly impacted the alpha diversity of the phytoplankton community. From March to July, with the average temperature increasing from 25.2℃ to 28.1℃,the Shannon or Species Richness were negatively correlated with temperature. During hot season (in Sep, average temperature 32.1℃), phytoplankton diversity was negatively correlated with nutrients (NH4 +, NO3 −, PO4 3−, TN). Additionally, during the rainy season, the Bray-Curtis similarity of the phytoplankton community was significantly lower than during the dry season. In March, the distance among the sampling sites was most strongly and positively correlated with the Bray-Curtis dissimilarity. Stochastic processes, specifically dispersal limitation and ecological drift, are the primary drivers of community assembly, while deterministic assembly processes (mainly heterogeneous selection) contribute a relatively minor portion (

Abstract Background Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Materials and methods Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques. Results In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P

IntroductionAsthma has an annual increasing morbidity rate and imposes a heavy social burden on public healthcare systems. The aim of this study was to use machine learning to identify asthma-specific genes for the prediction and diagnosis of asthma.MethodsDifferentially expressed genes (DEGs) related to asthma were identified by examining public sequencing data from the Gene Expression Omnibus, coupled with the support vector machine recursive feature elimination and least absolute shrinkage and selection operator regression model. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis and correlation analyses between gene and immune cell levels were performed. An ovalbumin-induced asthma mouse model was established, and eukaryotic reference transcriptome high-throughput sequencing was performed to identify genes expressed in mouse lung tissues.ResultsThirteen specific asthma genes were obtained from our dataset analysis (LOC100132287, CEACAM5, PRR4, CPA3, POSTN, LYPD2, TCN1, SCGB3A1, NOS2, CLCA1, TPSAB1, CST1, and C7orf26). The GO analysis demonstrated that DEGs linked to asthma were primarily related to positive regulation of guanylate cyclase activity, gpi anchor binding, peptidase activity and arginine binding. The renin-angiotensin system, arginine biosynthesis and arginine and proline metabolism were the key KEGG pathways of DEGs. Additionally, the genes CEACAM5, PRR4, CPA3, POSTN, CLCA1, and CST1 expression levels were positively associated with plasma cells and resting mast cells. The mouse model revealed elevated nos2 and clca1 expression in the asthmatic mouse group compared with that in normal mice, which was consistent with the findings in asthmatic patients.DiscussionThis study identified new marker genes for the prediction and diagnosis of asthma, which can be further validated and applied clinically

Background Glioblastoma (GBM) is an aggressive primary brain tumor with a high recurrence rate and poor prognosis. Necroptosis, a pathological hallmark of GBM, is poorly understood in terms of its role in prognosis, tumor microenvironment (TME) alteration, and immunotherapy.Methods & Results We assessed the expression of 55 necroptosis-related genes in GBM and normal brain tissues. We identified necroptosis-stratified clusters using Uni-Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression to establish the 10-gene Glioblastoma Necroptosis Index (GNI). GNI demonstrated significant prognostic efficacy in the TCGA dataset (n = 160) and internal validation dataset (n = 345) and in external validation cohorts (n = 591). The GNI-high subgroup displayed a mesenchymal phenotype, lacking the IDH1 mutation, and MGMT methylation. This subgroup was characterized by significant enrichment in inflammatory and humoral immune pathways with prominent cell adhesion molecules (CD44 and ICAM1), inflammatory cytokines (TGFB1, IL1B, and IL10), and chemokines (CX3CL1, CXCL9, and CCL5). The TME in this subgroup showed elevated infiltration of M0 macrophages, neutrophils, mast cells, and regulatory T cells. GNI-related genes appeared to limit macrophage polarization, as confirmed by immunohistochemistry and flow cytometry. The top 30% high-risk score subset exhibited increased CD8 T cell infiltration and enhanced cytolytic activity. GNI showed promise in predicting responses to immunotherapy and targeted treatment.Conclusions Our study highlights the role of necroptosis-related genes in glioblastoma (GBM) and their effects on the tumor microenvironment and patient prognosis. TheGNI demonstrates potential as a prognostic marker and provides insights into immune characteristics and treatment responsiveness.

Saccharina japonica is a commercially important species in the seaweed industry, with a long history of cultivation. Understanding the differences in the integrated quality of S. japonica across major production regions is necessary for achieving high-quality output and maximizing resource utilization efficiency. However, to date, comprehensive analyses and evaluations of S. japonica have received limited attention. In this study, we analyzed variations and characteristics of 17 physical and chemical indices of S. japonica from nine cultivated populations across the three primary producing provinces in China, namely Fujian, Liaoning and Shandong. Correlation and path analysis were used to explore the interrelationships among the indices, while hierarchical cluster analysis was used to further identify similarities and differences among populations. We employed two comprehensive analysis methods: grey correlation degree analysis (GCDA) and dynamic technique for order preference by similarity to ideal solution (DTOPSIS) to evaluate the integrated quality of S. japonica. The results showed that coefficients of variation for all physical and chemical indices were 9.4 %–54.6 %, with the color index b* exhibiting the greatest variability. Significant correlations were observed among the physical and chemical indices, and blade length and width were identified as key determinants of fresh weight. Moreover, physical and chemical indices showed significant differences among populations and producing provinces. S. japonica from Liaoning exhibited superior morphological traits, while samples from Shandong displayed better appearance color and higher mannitol content. According to the ranking from the two comprehensive analysis methods, S. japonica from Liaoning had the best overall integrated quality. These findings provide a foundation for the scientific evaluation of the integrated quality of cultivated S. japonica, offering insights for breeding and cultivation strategies, and promoting the high-value utilization of S. japonica.

Abstract Background Dendrobium officinale Kimura et Migo (D. officinale) is parasitic on rocks or plants with very few mineral elements that can be absorbed directly, so its growth and development are affected by nutritional deficiencies. Previous studies found that phosphorus deficiency promotes polysaccharides accumulation in D. officinale, the expression of DoCSLA6 (glucomannan synthase gene) was positively correlated with polysaccharide synthesis. However, the molecular mechanism by which the low phosphorus environment affects polysaccharide accumulation remains unclear. Results We found that DoSPX1 can reduce phosphate accumulation in plants and promote the expression of PSIs genes, thereby enhancing plant tolerance to low phosphorus environments.Y1H and EMSA experimental show that DoMYB37 can bind the promoter of DoCSLA6. DoSPX1 interact with DoMYB37 transiently overexpressed DoSPX1 and DoMYB37 in D. officinale protocorm-like bodies, decreased the Pi content, while increased the expression of DoCSLA6. Conclusions The signaling pathway of DoSPX1-DoMYB37-DoCSLA6 was revealed. This provides a theoretical basis for the accumulation of polysaccharide content in D. officinale under phosphorus starvation.

Abstract Objectives This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. Methods 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Results Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p

Abstract Background Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. Materials and methods This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. Results The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1. Conclusions Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract

Abstract Background and aim An increasing amount of research has indicated obesity greatly affects individuals with overactive bladder (OAB). However, traditional anthropometric methods present challenges in accurately assessing the likelihood of OAB. Hence, this study’s objective was to identify the correlation between the body roundness index (BRI) and OAB. Methods The research included 12,401 individuals who participated in the National Health and Nutrition Examination Survey spanning 2005–2018. The correlation between BRI and OAB was explored by using weighted multiple logistic regression and weighted restricted cubic spline (RCS). Subgroup analyses showed the associations based on different population types. The study also analyzed the predictive capability of various anthropometric indices, including BRI, body mass index, waist circumference, and weight, in assessing the likelihood of OAB through Receiver-operating characteristic (ROC) curves. Results An independent positive correlation between OAB and BRI was identified after adjusting for potential confounders in weighted multivariate logistic models[odds ratio (OR) = 1.15, 95% confidence interval (CI), 1.12–1.17]. Weighted RCS analysis found a positive dose-response correlation between OAB and BRI. The effect size of BRI on OAB remained stable across all prespecified subgroups (all P for interactions > 0.05). In ROC analysis, BRI showed better discriminatory ability for OAB compared with other anthropometric measures for both genders (all P

Microbial fertilizer is an environment-friendly fertilizer that can effectively improve the microecological environment of soil, playing an important role in the remediation of saline–alkali soil and promoting sustainable agricultural development. In this study, we examined the impact of microbial fertilizer application on saline–alkali field improvement over two years. The results indicated that, compared to NS0 and NS2 (the initial sowing period without microbial fertilizer addition), the soil pH and electrical conductivity (EC) levels significantly decreased by 4.1% and 8.49% and 60.56% and 39.66% for NS1 (after the first harvest) and NS3 (after the second harvest), respectively. Compared to NS0, the concentrations of Na+ and Cl−, among the eight major ions in the soil, decreased significantly by 87.23% and 80.91% in the second year, while Ca2+ increased significantly in NS1 and NS3, being 5.27 times and 2.46 times higher than before sowing. Comparing NS3 to NS0, the sodium adsorption ratio decreased by 87.04%. The activities of soil urease, alkaline phosphatase, and invertase in NS3 increased significantly by 90.18%, 45.67%, and 82.31% compared to those in NS0. In contrast, the activity of catalase decreased by 2.79% (p < 0.05). Alpha diversity analysis demonstrated that the Ace, Chao1, and Sobs indices for both bacteria and fungi were significantly higher at NS3 than before sowing, indicating the highest species richness at this stage. The Shannon index exhibited an ascending trend, and the difference in the Simpson index was not significant. After applying microbial fertilizer in the saline–alkali field, the number of bacterial and fungal operational taxonomic units (OTUs) significantly increased. In the bacteria, the proportion of Proteobacteria rose, while Actinobacteriota exhibited a significant reduction. Among fungi, the proportion of Ascomycota decreased and Basidiomycota increased. Principal component analysis (PCA) revealed distinct separation among treatments, indicating significant differences in microbial communities. Redundancy analysis (RDA) identified that the key physicochemical factors influencing bacterial community structure were available phosphorus (AP), electrical conductivity (EC), and pH, whereas for fungi, they were AP, available potassium (AK), and dissolved organic carbon (DOC). This research presents the effects of microbial fertilizer application on the improvement in a saline–alkali field over two years. It provides a scientific basis for the remediation of the saline–alkali field via microbe-induced changes in soil physicochemical properties, enzyme activity, microbial diversity, and community structure at different periods.

Mangroves, as blue carbon reservoirs, provide a unique habitat for supporting a variety of microorganisms. Among these, bacteria play crucial roles in the biogeochemical processes of mangrove sediments. However, little is known about their community composition, spatial distribution patterns, and environmental driving factors, particularly across the large geographical scales of mangrove wetlands. In this study, the composition and spatial distribution of the bacterial community structure and its response to fifteen physicochemical parameters (including temperature, pH, salinity, moisture, clay, silt, sand, organic carbon (OC), total nitrogen (TN), total phosphorus (TP), inorganic phosphorus (IP), organic phosphorus (OP), δ13C, δ15N, and carbon/nitrogen ratio (C/N ratio)) were characterized in 32 sampling locations of six different mangrove habitats from Guangxi, China, applying 16S rRNA gene high-throughput sequencing technology and correlation analysis. Our results indicated that the spatial distribution patterns in bacterial communities were significantly different among the six different mangrove sites, as evidenced by NMDS (non-metric multidimensional scaling), ANOSIM (analysis of similarity), and LDA (linear discriminant analysis) analysis. Composition analysis of bacterial communities showed that overall, Chloroflexi (8.3–31.6%), Proteobacteria (13.6–30.1%), Bacteroidota (5.0–24.6%), and Desulfobacterota (3.8–24.0%) were the most abundant bacterial phyla in the mangrove surface sediments. Redundancy analysis (RDA) further highlighted that salinity, δ13C, temperature, δ15N, and silt were the most critical environmental variables influencing the composition of bacterial communities across the whole mangrove samples. Notably, Chloroflexi, one of the most abundant bacterial phyla in the mangrove wetlands, displayed a significantly positive correlation with OC and a negative correlation with δ13C, suggesting its essential role in the degradation of terrestrial-derived organic carbon. These findings support the current understanding of the roles of the bacterial communities and their interactions with environmental factors in diverse mangrove ecosystems.

Abstract. Background:. Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients. Methods:. The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Results:. A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram. Conclusions:. We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

In recent years, Graph Convolutional Networks (GCNs) have emerged as a crucial methodology for handling graph-structured data, exhibiting superior performance in semi-supervised classification tasks. However, most existing GCNs encounter two main issues in real-world scenarios: 1) graph-structured data may be incomplete, for example, containing outlier nodes and noisy edges, which poses a great challenge for GCNs to extract the relation information for classification tasks; 2) the scarcity of labeled data, often limited to a few-shot scenario, hampers the ability of GCNs to learn comprehensive embedding representations. To cope with these issues, we propose a novel framework called pseudo labeling collaborative multi-channel graph convolutional networks (PCM-GCN). First, considering incomplete graph-structured data, we develop two modules: graph generation module and multi-channel fusion module. The graph generation module is designed to extend the raw data to multiple graphs, which avoids being constrained by the effective expression ability of the raw data. Meanwhile, the multi-channel fusion module integrates embeddings from multiple graphs, capturing the complementarity among multiple channels. Second, to address the problem of sparse labels, we develop a confidence-based pseudo labeling module, appending confident data with pseudo label to the labeled set to enlarge the training set. PCM-GCN leverages pseudo labeling to enhance multi-channel embedding fusion, resulting in rich and comprehensive node embedding representation. Extensive experiments on five benchmark datasets have shown that PCM-GCN surpasses other state-of-the-art methods in semi-supervised node classification tasks.

Abstract Background Diverse microbes, such as bacteria, are of immense worth to mangrove ecosystems due to their adaptability to salinity and variable environmental characteristics conditions. Pyridine and its derivatives compose most heterocyclic aromatic compounds largely produced by human activities that lead to environmental pollution. Bacteria have a crucial role in the nutrient cycling of carbon and nitrogen etc., to understand their functional involvement with environmental factors or ecosystem functioning as well as the species invasion and domestic or agriculture pyridine degradation pollution activities that threaten the mangrove ecosystem. Methods This work established the genetic-based molecular degradation of organic compounds in the mangrove ecosystem, which ultimately makes the availability of nutrients. As well as the effects of various abiotic factors on pyridine degradation to discover the pyridine degradation and the removal of ammonia nitrogen and the proposed nitrogen metabolism pathway. Results The novel bacterial strain NM1-A2 was isolated from mangrove sediments and, after 16S rRNA gene sequence analysis identified as Bacillus aryabhattai. NM1-A2 completely degraded pyridine within a 100 h incubation period at a temperature of 35 °C, an initial pH of 7.0, glucose and a pyridine concentration of 500 mg/L. The pseudo-first-order kinetics model described the pyridine biodegradation profile of NM1-A2 well. Interestingly, within 96 h the strain achieved almost complete pyridine degradation with a total organic carbon (TOC) removal of 87.9% ± 0.19% (from 377.52 ± 6.9 mg/L to 45.65 ± 0.14 mg/L). Within 96 h, the pyridine ring in the total nitrogen (TN) fraction at the maximum concentration of 55.31 ± 0.17 mg/L, furtherly 51.3% ± 2.39% of (TN) converted into Ammonia nitrogen (NH4 +-N). Furthermore, NM1-A2 exhibited its pyridine biodegradation activity decreased by only 4% after three consecutive cycles (48 h each). Moreover, NM1-A2 possessed nrt-ABCD nitrate transport family and gltABCD operons that participate in the activities of glutamine and glutamate synthetase in NH4 + conversion in the nitrogen cycle. Furthermore, the nitrogen metabolism genes (nrtA, nrtB, nrtC, nirB, nirD, gltB, gltD, glnA) exhibited expression in NM1-A2. Conclusion This research offers a potential treatment strategy for pyridine degradation in the mangrove ecosystem. Graphical Abstract

Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is the preferred treatment for EGFR-mutated lung cancer. However, acquired resistance inevitably develops. While non-coding RNAs have been implicated in lung cancer through various functions, the molecular mechanisms responsible for osimertinib resistance remain incompletely elucidated. Methods: RNA-sequencing technology was employed to determine differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) between H1975 and H1975OR cell lines. Starbase 2.0 was utilized to predict DE-lncRNA and DE-mRNA interactions, constructing ceRNA networks. Subsequently, functional and pathway enrichment analysis were performed on target DE-mRNAs to identify pathways associated with osimertinib resistance. Key target DE-mRNAs were then selected as potential risk signatures for lung adenocarcinoma (LUAD) prognostic modeling using multivariate Cox regression analyses. The Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry staining were used for result validation. Results: Functional analysis revealed that the identified DE-mRNAs primarily enriched in EGFR-TKI resistance pathways, especially in the PI3K/Akt signaling pathway, where their concerted actions may lead to osimertinib resistance. Specifically, upregulation of LINC00313 enhanced COL1A1 expression by acting as a miR-218-5p sponge, triggering an upstream response that activates the PI3K/Akt pathway, potentially contributing to osimertinib resistance. Furthermore, the expressions of LINC00313 and COL1A1 were validated by qRT-PCR, and the activation of the PI3K/Akt pathway was confirmed by immunohistochemistry staining. Conclusions: Our results suggest that the LINC00313/miR-218-5p/COL1A1 axis potentially contributes to osimertinib resistance through the PI3K/Akt signaling pathway, providing novel insights into the molecular mechanisms underlying acquired osimertinib resistance in LUAD. Additionally, our study may aid in the identification of potential therapeutic targets for overcoming resistance to osimertinib.

Galectins-8 (Gal-8), the tandem repeat sequences of the galectin family, can influence the pathophysiologic processes in neurological disorders. However, its effect on intracerebral hemorrhage and related mechanisms remains nebulous. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of Gal-8 on cellular and molecular immune inflammatory responses in hemorrhagic brain and evaluated the severity of short- and long-term brain injury. Our results showed that activated microglia in the periphery of hematoma in mice with intracerebral hemorrhage expressed Gal-8, while Gal-8 could regulate the expression of cytokines, such as HMGB-1 (P = 0.0032), TNF-α (P = 0.0158), and IL-10 (P = 0.0379). Inhibition of the glucose-binding activity of Gal-8 by thiogalactoside (TDG) significantly reduced the volume of cerebral hematoma (P = 0.0241) and hydrocephalus (P = 0.0112) during the acute phase of cerebral hemorrhage and improved the long-term prognosis. TDG can reduce acute-phase brain tissue injury and improve the prognosis by inhibiting the activation of immune-inflammatory cells in the periphery of hematoma and reducing the release of pro-inflammatory factors.

IntroductionUncertainty intolerance and perceived environmental uncertainty can influence an individual’s emotions and behavioral responses. Previous research showed that high uncertainty intolerance and high perceived environmental uncertainty were both negatively associated with an individual’s life satisfaction. We explored the interaction effects of uncertainty intolerance and perceived environmental uncertainty on ego depletion of early adulthood and its mechanisms.MethodsInvestigating 292 college students using an uncertainty intolerance scale, a perceived environmental uncertainty scale, a negative coping style questionnaire, and an ego depletion scale. The correlations among all variables were calculated using Pearson’s product-moment correlation coefficient, and then we used the PROCESS macro (model 8) in SPSS to test the conditional process model in the relationship between uncertainty intolerance and ego depletion.ResultsThe results showed that the interaction terms of uncertainty intolerance and perceived environmental uncertainty were significantly associated with negative coping styles. Only in the high perceived environmental uncertainty situations, uncertainty intolerance was positively associated with negative coping styles, and negative coping styles were positively associated with ego depletion.DiscussionIn general, compared with perceived environmental uncertainty, participants’ cognition towards environmental uncertainty was much more associated with individual’s coping styles and psychological state, individuals with high uncertainty intolerance would face great stress and experience more emotional problems. Our results suggest that it is important for individuals’ mental health to gain a sense of control in an uncertain environment and improve the tolerance of uncertainty. Future research needs to pay attention to the intervention strategy of decreasing uncertainty intolerance.

Lewis Fry Richardson proposed his famous picture of turbulent flows in 1922, where the kinetic energy is transferred from large-scale to small-scale structures until the viscosity converts it into heat. This cascade idea, also known as the forward energy cascade, is now widely accepted and is treated as the cornerstone of not only turbulent modeling, but also global circulation models of the ocean and atmosphere. In this work, the Filter-Space-Technique is applied to the oceanic flow field provided by the CMEMS reanalysis model to quantify the scale-to-scale energy flux. A rich dynamical pattern associated with different scales is observed. More precisely, either positive or negative fluxes are observed, indicating the direction of the energy cascade, where the energy is transferred from large-scale structures to small-scale ones or vice versa. High-intensity energy exchange is found mainly in the Western Boundary Current Systems and Equatorial Counter Currents. For the latter case, a wavelike pattern is observed on the westward travel. Moreover, strong seasonal variation is evident for some scales and regions. These results confirm the existence of forward and inverse cascades and rich regional dynamics.

Litopenaeus vannamei is one of the important crustaceans in aquaculture in China. In recent years, the shrimp culture industry has gradually developed into an intensive and high-density model, which can lead to environmental deterioration and large-scale outbreak of diseases. The widespread use of antibiotics has led to the increase of pathogen drug resistance, environmental pollution, and ecological imbalance, resulting in secondary pollution in the water. Probiotics are live microbial additives that promote good health and are environmentally sustainable and safe for use. They are often used as important substitutes for antibiotics. Brevibacillus laterosporu, as a biocontrol probiotic, is commonly used for disease control of crops, animals, and poultry, but its use is rarely reported in aquaculture. A 28-day breeding experiment was carried out with L. vannamei weighing (1.00±0.08) g, to study the effects of adding B. laterosporu FAS05 in the feed on the growth, disease resistance, and immunity of L. vannamei. The experiment was divided into four groups with three replicates in each group, and 50 shrimps in each replicate were fed with the experimental feed supplemented with 0 CFU/g (group C, as the control group), 105 CFU/g (group BL1), 107 CFU/g (group BL2), and 109 CFU/g (group BL3) of B. laterosporu FAS05. B. laterosporu FAS05 was isolated from the aquaculture pond with a low number of Vibrio in summer. The bacterium was added into the basic feed with fish meal, soybean meal, and corn meal as the main protein source, fish oil and phospholipid oil were added as the fat source, wheat flour as the main sugar source, and inorganic salts and vitamins as supplements. L. vannamei was purchased from a prawn farm in Weihai City, Shandong Province. The temperature was 25–28 ℃ and the salinity was 27–30. During the breeding experiment, eight shrimps were randomly selected in each tank every two weeks and their body length, weight, and plumpness were measured. The phagocytic activity assay was modified on the basis of the method reported by Delaporte et al (2003). Fl-1 channel flow cytometry was used to detect and analyze the offset of respiratory burst peak. The blood lymphocytes, serum, and hepatopancreas of shrimp were collected 24 hours after the experiment. The activities of immune related enzymes in hepatopancreas, such as superoxide dismutase (SOD), catalase (CAT), acid phosphatase (ACP), and alkaline phosphatase (ALP) levels, and the activities of immune related enzymes in serum, phenol oxidase (PO), and lysozyme (LZM), were determined by kits. The phagocytic activity was measured, and the assay was modified on the basis of Delaporte et al (2003). Fl-1 channel flow cytometry was used to detect and analyze the offset of respiratory burst peak. After the feeding test, a one-week infection test of Vibrio parahaemolyticus was carried out to determine disease resistance. The experimental results were expressed as Mean±SD. One-way ANOVA analysis was conducted for all data using statistical software SPSS 16.0, and significance level was defined as P < 0.05. LSD homogeneity of variance test was used to compare the differences between experimental treatment groups and control groups. The results showed that there was no significant difference in survival rate among all groups (P > 0.05), and the body length, body weight, and specific growth rate of shrimps in the BL1 and BL2 groups were significantly higher than those in group C (P < 0.05). Compared to that in group C, the abundance of Vibrio in the aquaculture water in the BL1 to BL3 groups was significantly decreased (P < 0.05). After infection with V. parahemolyticus, the survival rate of group C was about 45%, while the survival rate of the BL1 to BL3 groups was more than 80%; therefore, the survival rate of the BL1 to BL3 groups was significantly higher than that in group C (P < 0.05), and no significant difference was found among the BL1 to BL3 groups (P > 0.05). Compared to that of group C, the phagocytizing rate of shrimp blood cells in the BL1 to BL3 groups increased significantly (P < 0.05), while the production of ROS in blood cells decreased significantly (P < 0.05). The LZM, CAT and ACP activities of shrimps in the BL1 to BL3 groups were significantly higher than those in group C (P < 0.05). There was no significant difference in LZM and ACP activities among the BL1 to BL3 groups (P > 0.05). The PO of shrimps in the BL2 group was significantly higher than those in other groups (P < 0.05). The ALP and SOD in the BL1 and BL2 groups were significantly higher than those in group C and BL3 (P < 0.05). The above results showed that B. laterosporu FAS05 as a feed additive could promote the growth of shrimp, activate the immune system, improve disease resistance, and inhibit the growth of Vibrio in the surrounding environment. The reference dosage was 105 CFU/g. When the infection is serious, the dosage can be increased to 107 CFU/g to further improve the non-specific immunity of shrimp. The results of this study can provide basic data for the application of B. laterosporu FAS05 in shrimp culture and production.

This study analyzed flower bud differentiation and fruiting stages to investigate how the structure of the plant endophytic microbial community in the roots of tomatoes changes with plant senescence. Based on high-throughput sequencing technology, the diversity and relative abundance of endophytic microorganisms (bacteria and fungi) in tomato stems at different growth stages were analyzed. At the same time, based on LEfSe analysis, the differences in endophytic microorganisms in tomato stems at different growth stages were studied. Based on PICRUSt2 function prediction and FUNGuild, we predicted the functions of endophytic bacterial and fungal communities in tomato stems at different growth stages to explore potential microbial functional traits. The results demonstrated that not only different unique bacterial genera but also unique fungal genera could be found colonizing tomato roots at different growth stages. In tomato seedlings, flower bud differentiation, and fruiting stages, the functions of colonizing endophytes in tomato roots could primarily contribute to the promotion of plant growth, stress resistance, and improvement in nutrient cycling, respectively. These results also suggest that different functional endophytes colonize tomato roots at different growth stages.

IntroductionGroup 2 innate lymphoid cells (ILC2s) play a crucial role in house dust mite (HDM)-induced allergic inflammation, and allergen immunotherapy (AIT) holds promise for treating the disease by reducing the frequency of ILC2s. Despite significant progress in AIT for allergic diseases, there remains a need to improve the control of allergic symptoms.MethodsWe investigated the synergistic effect of the Notch signaling pathway and subcutaneous immunotherapy (SCIT) in treating allergic airway inflammation in mice and their impact on the ratio of ILC2s in lung tissues. This was achieved by establishing the HDM-induced airway allergic disorders (HAAD) model and SCIT model. Additionally, we conducted in vitro investigations into the effect of the Notch signaling pathway on the secretory function of activated ILC2s using fluorescence-activated cell sorting. Furthermore, we explored the coactivation of the Notch signaling pathway with SCIT in vitro by sorting ILC2s from the lung tissues of mice after SCIT modeling.ResultsPreviously, our group demonstrated that Notch signaling pathway inhibitors can reduce allergic airway inflammation in mice. Notch signaling induces lineage plasticity of mature ILC2s. In this study, we showed that AIT alleviates allergic airway inflammation and suppresses the frequency of ILC2s induced by HDM. Interestingly, AIT combined with a γ-secretase inhibitor (GSI), an inhibitor of the Notch signaling pathway, significantly inhibited the frequency of ILC2s, reduced airway inflammation, and suppressed Th2-type responses in a mouse model. Furthermore, lung ILC2s from HDM-challenged mice with or without AIT were treated with GSI in vitro, and we found that GSI dramatically reduced the secretion of type 2 inflammatory factors in ILC2s.DiscussionThese findings suggest that Notch signaling pathway inhibitors can be used as adjuvant therapy for AIT and may hold potential treatment value in the cooperative control of allergic airway inflammation during early AIT.

Melittin, a classical antimicrobial peptide, is a highly potent antitumor agent. However, its significant toxicity seriously hampers its application in tumor therapy. In this study, we developed novel melittin analogs with pH-responsive, cell-penetrating and membrane-lytic activities by replacing arginine and lysine with histidine. After conjugation with camptothecin (CPT), CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions. Notably, we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus. CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity. Collectively, the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

Interleukin-17A (IL-17A) levels are elevated in patients with asthma. Ferroptosis has been identified as the non-apoptotic cell death type associated with asthma. Data regarding the relation of ferroptosis with asthma and the effect of IL-17A on modulating ferroptosis in asthma remain largely unclear. The present work focused on investigating the role of IL-17A in allergic asthma-related ferroptosis and its associated molecular mechanisms using public datasets, clinical samples, human bronchial epithelial cells, and an allergic asthma mouse model. We found that IL-17A was significantly upregulated within serum in asthma cases. Adding IL-17A significantly increased ferroptosis within human bronchial epithelial cells (BEAS-2B). In ovalbumin (OVA)-induced allergic asthmatic mice, IL-17A regulated and activated lipid peroxidation induced ferroptosis, whereas IL-17A knockdown effectively inhibited ferroptosis in vivo by protection of airway epithelial cells via the xCT-GSH-GPX4 antioxidant system and reduced airway inflammation. Mouse mRNA sequencing results indicated that the tumor necrosis factor (TNF) pathway was the differential KEGG pathway in the OVA group compared to healthy controls and the OVA group compared to the IL-17A knockout OVA group. We further used N-acetylcysteine (TNF inhibitor) to inhibit the TNF signaling pathway, which was found to protect BEAS-2B cells from IL-17A induced lipid peroxidation and ferroptosis damage. Our findings reveal a novel mechanism for the suppression of ferroptosis in airway epithelial cells, which may represent a new strategy for the use of IL-17A inhibitors against allergic asthma.

Objective: The aim of our study was to investigate whether the Dietary Inflammatory Index (DII) correlated with gout in American adults. Method: The study used data from the 2007–2018 National Health and Nutrition Examination Survey, with 27,710 adults participating. Initially, multivariable analysis was performed, with controls for covariates, to assess the link of DII and gout. Then, restricted cubic splines (RCS) were applied to model the nonlinear relationship of DII and gout. Furthermore, propensity score matching (PSM) as a further study of potential relationships was established. Eventually, subgroup analysis was performed. Result: Participants within the highest DII quartile would be more susceptible to increased risk of gout in the univariate regression model (Q4 vs. Q1, OR = 1.31, CI: 1.05–1.63). Additionally, a positive correlation was detected between gout risk and DII after adjusting on drinking, smoking, gender, race, age, and BMI. Based on RCS analysis, we observed that the risk of gout raised sharply as DII values increased, then flattened, and increased sharply again when the DII was greater than approximately 2.5. After performing the PSM, it was observed that DII correlated in a positive way to the presence of gout on a fully adjusted multivariable model. Subgroup analysis revealed that the link of DII and gout showed no statistical significance in females, blacks, Mexicans, nor in the population that smoked. Conclusion: Greater degrees of pro-inflammation correlate with a higher risk of gout and might be a predisposing factor for gout. Hence, tactics fostering an anti-inflammatory diet for preventing and improving gout in adults should be regarded.

Abstract Background The treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis. Methods The principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods. Results Based on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p

Abstract Shotgun metagenome sequencing provides the opportunity to recover underexplored rare populations and identify difficult-to-elucidate biochemical pathways. However, information on sulfur genes, including their sequences, is scattered in public databases. Here, we introduce SMDB ( https://smdb.gxu.edu.cn/ )—a manually curated database of sulfur genes based on an in-depth review of the scientific literature and orthology database. The SMDB contained a total of 175 genes and covered 11 sulfur metabolism processes with 395,737 representative sequences affiliated with 110 phyla and 2340 genera of bacteria/archaea. The SMDB was applied to characterize the sulfur cycle from five habitats and compared the microbial diversity of mangrove sediments with that of other habitats. The structure and composition of microorganism communities and sulfur genes were significantly different among the five habitats. Our results show that microorganism alpha diversity in mangrove sediments was significantly higher than in other habitats. Genes involved in dissimilatory sulfate reduction were abundant in subtropical marine mangroves and deep-sea sediments. The neutral community model results showed that microbial dispersal was higher in the marine mangrove ecosystem than in others habitats. The Flavilitoribacter of sulfur-metabolizing microorganism becomes a reliable biomarker in the five habitats. SMDB will assist researchers to analyze genes of sulfur cycle from the metagenomic efficiently.

There are approximately 2.2 billion people around the world with varying degrees of visual impairments. Among them, individuals with severe visual impairments predominantly rely on hearing and touch to gather external information. At present, there are limited reading materials for the visually impaired, mostly in the form of audio or text, which cannot satisfy the needs for the visually impaired to comprehend graphical content. Although many scholars have devoted their efforts to investigating methods for converting visual images into tactile graphics, tactile graphic translation fails to meet the reading needs of visually impaired individuals due to image type diversity and limitations in image recognition technology. The primary goal of this paper is to enable the visually impaired to gain a greater understanding of the natural sciences by transforming images of mathematical functions into an electronic format for the production of tactile graphics. In an effort to enhance the accuracy and efficiency of graph element recognition and segmentation of function graphs, this paper proposes an MA Mask R-CNN model which utilizes MA ConvNeXt as its improved feature extraction backbone network and MA BiFPN as its improved feature fusion network. The MA ConvNeXt is a novel feature extraction network proposed in this paper, while the MA BiFPN is a novel feature fusion network introduced in this paper. This model combines the information of local relations, global relations and different channels to form an attention mechanism that is able to establish multiple connections, thus increasing the detection capability of the original Mask R-CNN model on slender and multi-type targets by combining a variety of multi-scale features. Finally, the experimental results show that MA Mask R-CNN attains an 89.6% mAP value for target detection and 72.3% mAP value for target segmentation in the instance segmentation of function graphs. This results in a 9% mAP improvement for target detection and 12.8% mAP improvement for target segmentation compared to the original Mask R-CNN.

Abstract Background Previous research has demonstrated that harsh parenting negatively affects children’s psychological development. This study examined the association between harsh parenting during childhood and life satisfaction of Chinese college students. We further looked at whether this association is explained in part by negative coping styles, and whether peer support lessens the potential effect of harsh parenting on negative coping styles and life satisfaction. Method The sample included 609 Chinese students (aged 17–21 years, M = 18.39, SD = 0.82). The participants responded to questionnaires measuring past experiences with harsh parenting, life satisfaction, negative coping styles, and peer support. Results Regression analysis showed that harsh parenting negatively contributed to students’ life satisfaction via the mediator of negative coping styles, and peer support moderated this negative relationship. Specifically, the negative impact of harsh parenting on life satisfaction was only significant when there was low peer support. The effect of harsh parenting on negative coping styles was higher in individuals with high peer support than in those with low peer support. Conclusion This study highlights the roles of intrinsic (negative coping style) and extrinsic (peer support) factors in understanding the negative effects of harsh parenting on adolescents’ life satisfaction. These results provide insight into how to enhance adolescents’ life satisfaction by reducing harsh parenting and negative coping styles and by promoting peer support.

Nerium oleander is an important medicinal plant. In order to study the diversity of endophytic fungi from N. oleander and evaluate the activity of its secondary metabolites, the endophytic fungi of N. oleander in Guangxi were isolated and purified, and identified by a combination of morphology and ITS sequence analysis. Then the antibacterial activities of endophytic fungus extracts were screened with five indicator bacteria (including three Vibrio species). The results were as follows: (1) A total of 19 endophytic fungi were obtained from Guangxi N. oleander. The ITS sequence analysis showed that these 19 endophytic fungi all belonged to the Ascomycota, and covered five orders and seven genera, which including Colletotrichum, Guignardia, Phyllosticta, Neofusicoccum, Aspergillus, Nothophoma and Diaporthe. Among them, the dominant genera were Colletotrichum (the separation rate was 36.85%) and Guignardia (the isolation rate was 21.05%). Colletotrichum was mainly distributed on stems, and Guignardia all originated from leaves. (2) Antibacterial experiments showed that jing-117 (Neofusicoccum sp.) and ye-130 (Guignardia sp.) had specific antibacterial effects on Vibrio campbellii, ye-136 (Aspergillus sp.) could simultaneously inhibit Bacillus cereus and Vibrio campbellii. ye-135 (Aspergillus sp.) and jing-116 (Colletotrichum sp.) could only inhibit B. cereus, and ye-134 (Guignardia sp.) had an inhibitory activity to Vibrio alginolyticus. The study revealed for the first time that endophytic fungi of N. oleander in Guangxi has a relatively rich diversity based on the ITS sequence. Some antibacterial active strains could be screened, and their extracts could inhibit the growth of aquatic pathogen Vibrio, which will has good development value in the future.

Abstract Background The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. Methods We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). Results During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p

The purpose of this study was to explore the effect of parental emotional neglect on the academic procrastination of late adolescents and further analyze the mediating role of future self-continuity and ego depletion. This study included 609 college students, 344 males and 265 females, ranging in age from 17 to 21 years (M = 18.39, SD = 0.82), who responded to four questionnaires measuring parental emotional neglect, academic procrastination, future self-continuity, and ego depletion, respectively. The results showed that future self-continuity and ego depletion mediated the association between parental emotional neglect and late adolescents’ academic procrastination in a serial pattern. Perceived higher levels of parental emotional neglect correlated with lower future self-continuity and higher ego depletion in these late adolescents, leading to higher levels of academic procrastination.

Osthole is widely used in medicine because of its anti-oxidative, anti-allergenic and anti-inflammatory. In this study, we explored the protective effects of osthole on food allergenic mice and investigated its potential mechanism of action. We first established a food allergic mouse model by intraperitoneal sensitization and OVA (ovalbumin) oral challenge. Osthole were orally administered before OVA challenge. Diarrhea and allergy scores were used to assess food allergy symptoms. The pathological changes of the intestine were examined by H&E staining and electron microscopy. OVA-IgE, mucosal mast cell protease-1 (mMCP-1), IL-33, ST2, group 2 innate lymphoid cell (ILC2), and regulatory T (Treg) related-cytokine levels were assessed.We found that the oral administration of osthole after OVA sensitization could improve food allergy symptoms and induce beneficial intestinal pathological changes in mice. Osthole reduce the levels of IgE and mMCP-1 and inhibited the IL33/ST2 signaling pathway, thereby blocking ILC2 response and improving Treg response.

Attribute reduction is a core technique in the rough set domain and an important step in data preprocessing. Researchers have proposed numerous innovative methods to enhance the capability of attribute reduction, such as the emergence of multi-granularity rough set models, which can effectively process distributed and multi-granularity data. However, these innovative methods still have numerous shortcomings, such as addressing complex constraints and conducting multi-angle effectiveness evaluations. Based on the multi-granularity model, this study proposes a new method of attribute reduction, namely using multi-granularity neighborhood information gain ratio as the measurement criterion. This method combines both supervised and unsupervised perspectives, and by integrating multi-granularity technology with neighborhood rough set theory, constructs a model that can adapt to multi-level data features. This novel method stands out by addressing complex constraints and facilitating multi-perspective effectiveness evaluations. It has several advantages: (1) it combines supervised and unsupervised learning methods, allowing for nuanced data interpretation and enhanced attribute selection; (2) by incorporating multi-granularity structures, the algorithm can analyze data at various levels of granularity. This allows for a more detailed understanding of data characteristics at each level, which can be crucial for complex datasets; and (3) by using neighborhood relations instead of indiscernibility relations, the method effectively handles uncertain and fuzzy data, making it suitable for real-world datasets that often contain imprecise or incomplete information. It not only selects the optimal granularity level or attribute set based on specific requirements, but also demonstrates its versatility and robustness through extensive experiments on 15 UCI datasets. Comparative analyses against six established attribute reduction algorithms confirms the superior reliability and consistency of our proposed method. This research not only enhances the understanding of attribute reduction mechanisms, but also sets a new benchmark for future explorations in the field.

Granular computing (GrC) is a methodology for reducing the complexity of problem solving and includes two basic aspects: granulation and granular-based computing. Strongly connected components (SCCs) are a significant subgraph structure in digraphs. In this paper, two new granulation strategies were devised to improve the efficiency of computing SCCs. Firstly, four SCC correlations between the vertices were found, which can be divided into two classes. Secondly, two granulation strategies were designed based on correlations between two classes of SCCs. Thirdly, according to the characteristics of the granulation results, the parallelization of computing SCCs was realized. Finally, a parallel algorithm based on granulation strategy for computing SCCs of simple digraphs named GPSCC was proposed. Experimental results show that GPSCC performs with higher computational efficiency than algorithms.

As an acute and highly lethal infectious disease, there is no specific therapeutic drug for canine distemper (CD). Although the process of large-scale production of canine distemper virus (CDV) vaccine of mink has been greatly improved, there are still many deficiencies to be perfected. As one of the most promising technologies for large-scale vaccine production, microcarrier suspension culture technology needs to be further improved. In this study, the application effect of the new Cephodex microcarrier in CDV culture was evaluated to establish a set of technical process for DF-1 cell high-density growth and CDV efficient proliferation. To perfect the large-scale CDV production process, Cephodex was used to suspension culture DF-1 cells for proliferating CDV. In a shake flasks culture system, the optimal culture conditions were established by optimizing culture temperature, virus inoculation and harvest time. Therefore, mink CD vaccine high-efficiency production was laid on the preliminarily established technology of CDV microcarrier suspension culture. The cell density could reach over 3×106 cells/mL after 72 h cultured with Cephodex microcarrier at 37°C. Proliferated at 35°C, the CDV titer after 72 h was about 100.5 TCID50/0.1ml higher than that at 33°C and 37°C. These results show that the Cephodex microcarrier could be used for large-scale culture of DF-1 cells and efficient proliferation of CDV.

Abstract Aims Recent studies suggested that both left ventricular ejection fraction (LVEF) lower than 60% or higher than 65% were associated with an increased mortality in the general population. Uncertainty remains regarding adverse outcomes across LVEF in coronary artery disease (CAD). The common understanding was that LVEF 40%. We aimed to evaluate the relationship between LVEF and mortality or adverse events in CAD patients undergoing percutaneous coronary intervention (PCI). Methods and results A total of 10 252 CAD patients undergoing PCI from an observational cohort were studied. All‐cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) were set as outcomes. Kaplan–Meier curves, adjusted Cox regression models, and restricted cubic spline analyses were used for evaluation. A total of 137 (1.3%) patients had all‐cause mortality, and 816 (8.0%) patients had MACCE during a median of 2.4 years of follow‐up. The median LVEF was 64%. All‐cause mortality and MACCE rates changed substantially across LVEF categories, and a linear inverse relationship of LVEF with all‐cause mortality and MACCE risk was observed. All‐cause mortality or MACCE risk increased significantly below an LVEF of 55 or 65%, respectively. Patients with LVEF

As the only semi-enclosed sea area in China, the Bohai Sea is the strategic support and key support for the vigorous development of Beijing-Tianjin-Hebei Urban Agglomeration. The stability of its ecological environment is closely related to the well-being of coastal human beings, and its ecological environment restoration has become a research hotspot in recent years. This study focused on the analysis of the impact of global climate change and human activities on the ecological environment of the Bohai Sea, and comprehensively compared and analyzed the successful cases of ecological restoration in similar waters at home and abroad. Based on the characteristics and present situation of the Bohai Sea, some ecological restoration principles such as dynamic thinking and holistic preservation, habitat connectivity restoration principles, and different spatio-temporal scale restoration principle were proposed. It also pointed out that the ecological restoration of the Bohai Sea required rational planning of fishery economic activities, and overall consideration of the relationship between the Bohai Sea ecology and flushing water. It was recommended to use a forward-looking thinking model and concept, reasonably predict, plan, locate, configure, implement and maintain the stability of the Bohai Sea ecosystem, and focus on exploring the best adaptive management strategies to deal with global climate change.

Background: Hypoxia is known to play a critical role in tumor occurrence, progression, prognosis, and therapy resistance. However, few studies have investigated hypoxia markers for diagnosing and predicting prognosis in colon adenocarcinoma (COAD). This study aims to identify a hypoxia genes-based biomarker for predicting COAD patients’ prognosis and response to immunotherapy on an individual basis. Methods: Hypoxia-related genes were extracted from the Molecular Signatures Database. Gene expression, clinical data, and mutation data of COAD were collected retrospectively from the Cancer Genome Atlas, the Gene Expression Omnibus, and the International Cancer Genome Consortium databases. Univariate and multivariate cox regression, and the least absolute shrinkage and selection operator method were used to select the genes most associated with the prognosis of COAD patients. Kaplan–Meier survival analysis, receiver operating characteristic curves, calibration curves, and decision curve analyses were performed to validate the efficacy of the signature in predicting the prognosis of COAD patients. EdU incorporation assays, cell survival assays, western blot assays, and trans-well invasion assays were performed to further confirm the function of the screened genes in tumorigenesis. Results: ENO3 and KDM3A were identified as key genes for constructing prognostic and diagnostic signatures, which were found to be independent risk factors for predicting the prognosis and diagnosis of COAD patients. Using these signatures, COAD patients could be stratified into high-risk and low-risk groups, with the latter exhibiting better overall survival outcomes. Moreover, the high-risk group displayed elevated levels of immune checkpoint genes and tumor mutation burden, indicating that these patients may benefit from immune checkpoint inhibitor therapy. Conclusion: The signature developed in this study demonstrates excellent efficacy in prognosticating the outcomes of COAD patients. Moreover, it can serve as a valuable tool for clinicians to identify COAD patients who are suitable for ICI therapy.

BackgroundGliomas are the most common primary tumors of the central nervous system, with high heterogeneity and highly variable survival rates. Accurate classification and prognostic assessment are key to the selection of treatment strategies. One hallmark of the tumor is resistance to cell death. PANoptosis, a novel mode of programmed cell death, has been frequently reported to be involved in the innate immunity associated with pathogen infection and played an important role in cancers. However, the intrinsic association of PANoptosis with glioma requires deeper investigation.MethodsThe genetics and expression of the 17 reported PANoptosome-related genes were analyzed in glioma. Based on these genes, patients were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between clusters, a prognostic model called PANopotic score was constructed after univariate Cox regression, LASSO regression, and multivariate Cox regression. The expression of the 5 genes included in the PANopotic score was also examined by qPCR in our cohort. The prognostic differences, clinical features, TME infiltration status, and immune characteristics between PANoptotic clusters and score groups were compared, some of which even extended to pan-cancer levels.ResultsGene mutations, CNVs and altered gene expression of PANoptosome-related genes exist in gliomas. Two PANoptotic clusters were significantly different in prognosis, clinical features, immune characteristics, and mutation landscapes. The 5 genes included in the PANopotic score had significantly altered expression in glioma samples in our cohort. The high PANoptotic score group was inclined to show an unfavorable prognosis, lower tumor purity, worse molecular genetic signature, and distinct immune characteristics related to immunotherapy. The PANoptotic score was considered as an independent prognostic factor for glioma and showed superior prognostic assessment efficacy over several reported models. PANopotic score was included in the nomogram constructed for the potential clinical prognostic application. The associations of PANoptotic score with prognostic assessment and tumor immune characteristics were also reflected at the pan-cancer level.ConclusionMolecular subtypes of glioma based on PANoptosome-related genes were proposed and PANoptotic score was constructed with different clinical characteristics of anti-tumor immunity. The potential intrinsic association between PANoptosis and glioma subtypes, prognosis, and immunotherapy was revealed.

Aerosols play a crucial role in the surface radiative budget by absorbing and scattering both shortwave and longwave radiation. While most aerosol types exhibit a relatively minor longwave radiative forcing when compared to their shortwave counterparts, dust aerosols stand out for their substantial longwave radiative forcing. In this study, radiometers, a sun photometer, a microwave radiometer and the parameterization scheme for clear-sky radiation estimation were integrated to investigate the radiative properties of aerosols. During an event in Xianghe, North China Plain, from 25 April to 27 April 2018, both the composition (anthropogenic aerosol and dust) and the aerosol optical depth (AOD, ranging from 0.3 to 1.5) changed considerably. A notable shortwave aerosol radiative effect (SARE) was revealed by the integrated system (reaching its peak at −131.27 W·m−2 on 26 April 2018), which was primarily attributed to a reduction in direct irradiance caused by anthropogenic aerosols. The SARE became relatively consistent over the three days as the AODs approached similar levels. Conversely, the longwave aerosol radiative effect (LARE) on the dust days ranged from 8.94 to 32.93 W·m−2, significantly surpassing the values measured during the days of anthropogenic aerosol pollution, which ranged from 0.35 to 28.67 W·m−2, despite lower AOD values. The LARE increased with a higher AOD and a lower Ångström exponent (AE), with a lower AE having a more pronounced impact on the LARE than a higher AOD. It was estimated that, on a daily basis, the LARE will offset approximately 25% of the SARE during dust events and during periods of heavy anthropogenic pollution.

Abstract Transcatheter arterial chemoembolization (TACE) is one of the main palliative therapies for advanced hepatocellular carcinoma (HCC), which is also regarded as a promising therapeutic strategy for cancer treatment. However, drug-loaded microspheres (DLMs), as commonly used clinical chemoembolization drugs, still have the problems of uneven particle size and unstable therapeutic efficacy. Herein, gelatin was used as the wall material of the microspheres, and homogenous gelatin microspheres co-loaded with adriamycin and Fe3O4 nanoparticles (ADM/Fe3O4-MS) were further prepared by a high-voltage electrospray technology. The introduction of Fe3O4 nanoparticles into DLMs not only provided excellent T2-weighted magnetic resonance imaging (MRI) properties, but also improved the anti-tumor effectiveness under microwave-induced hyperthermia. The results showed that ADM/Fe3O4-MS plus microwave irradiation had significantly better antitumor efficacy than the other types of microspheres at both cell and animal levels. Our study further confirmed that ferroptosis was involved in the anti-tumor process of ADM/Fe3O4-MS plus microwave irradiation, and ferroptosis marker GPX4 was significantly decreased and ACSL4 was significantly increased, and ferroptosis inhibitors could reverse the tumor cell killing effect caused by ADM/Fe3O4-MS to a certain extent. Our results confirmed that microwave mediated hyperthermia could amplify the antitumor efficacy of ADM/Fe3O4-MS by activating ferroptosis and the introduction of Fe3O4 nanoparticles can significantly improve TACE for HCC. This study confirmed that it was feasible to use uniform-sized gelatin microspheres co-loaded with Fe3O4 nanoparticles and adriamycin to enhance the efficacy of TACE for HCC. Graphical Abstract

Chia is an annual crop whose seeds have the highest content of α-linolenic acid (ALA) of any plant known to date. We generated a high-quality assembly of the chia genome using circular consensus sequencing (CCS) of PacBio. The assembled six chromosomes are composed of 21 contigs and have a total length of 361.7 Mb. Genome annotation revealed a 53.5% repeat content and 35,850 protein-coding genes. Chia shared a common ancestor with Salvia splendens ~6.1 million years ago. Utilizing the reference genome and two transcriptome datasets, we identified candidate fatty acid desaturases responsible for ALA biosynthesis during chia seed development. Because the seed of S. splendens contains significantly lower proportion of ALA but similar total contents of unsaturated fatty acids, we suggest that strong expression of two ShFAD3 genes are critical for the high ALA content of chia seeds. This genome assembly will serve as a valuable resource for breeding, comparative genomics, and functional genomics studies of chia.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Abstract Background Tumor microenvironments are characterized by resistance to chemotherapeutic agents and radiotherapy. Hypoxia plays an important role in the development of tumor resistance, as well as the generation of metastatic potential. YAP also participates in the regulation of hypoxia-mediated chemoresistance, and is negatively regulated by protein tyrosine phosphatase non-receptor type 14 (PTPN14). Methods The PTPN14 expression in hepatocellular carcinoma (HCC) tissues were evaluated by qRT-PCR, western blot and tissue microarrays. The effect of PTPN14 on HCC progression was investigated in vitro and in vivo. Results Here, we report that PTPN14 expression was downregulated in HCC tissues and cell lines. Silencing PTPN14 significantly enhanced proliferation, migration, invasion of HepG2 cells in vitro and tumor growth and metastasis in vivo, whereas overexpression of PTPN14 significantly inhibited these abilities in SK-Hep1 cells. We also found that hypoxia-induced nuclear translocation and accumulation of PTPN14 led to resistance to sorafenib in HCC cells. Further mechanistic studies suggested that NPM1 regulates PTPN14 localization, and that NPM1 regulates YAP by retaining PTPN14 in the nucleus under hypoxic conditions. Conclusions These data suggest that a therapeutic strategy against chemoresistant HCC may involve disruption of NPM1-mediated regulation of YAP by retaining PTPN14 in the nucleus under hypoxic conditions.

Porous titanium is an excellent bone-implant biomaterial. This article uses SiC as a reinforcing agent to compound into porous titanium materials to improve the mechanical properties of porous titanium as medical materials. Porous titanium with different SiC(0–7.5wt.%) content was prepared by the conventional powder metallurgy method. Results revealed that SiC significantly improves porous titanium's densification and sintering properties. Moreover, when the SiC content is 3wt.%, the compressive capacity of porous titanium reaches 191.1Mpa. Likewise, the addition of SiC significantly improves the hardness and strength.

ObjectiveThis study aimed to analyze and visualize the current research focus, research frontiers, evolutionary processes, and trends of artificial intelligence (AI) in the field of gastric cancer using a bibliometric analysis.MethodsThe Web of Science Core Collection database was selected as the data source for this study to retrieve and obtain articles and reviews related to AI in gastric cancer. All the information extracted from the articles was imported to CiteSpace to conduct the bibliometric and knowledge map analysis, allowing us to clearly visualize the research hotspots and trends in this field.ResultsA total of 183 articles published between 2017 and 2022 were included, contributed by 201 authors from 33 countries/regions. Among them, China (47.54%), Japan (21.86%), and the USA (13.11%) have made outstanding contributions in this field, accounting fsor 82.51% of the total publications. The primary research institutions were Wuhan University, Tokyo University, and Tada Tomohiro Inst Gastroenterol and Proctol. Tada (n = 12) and Hirasawa (n = 90) were ranked first in the top 10 authors and co-cited authors, respectively. Gastrointestinal Endoscopy (21 publications; IF 2022, 9.189; Q1) was the most published journal, while Gastric Cancer (133 citations; IF 2022, 8.171; Q1) was the most co-cited journal. Nevertheless, the cooperation between different countries and institutions should be further strengthened. The most common keywords were AI, gastric cancer, and convolutional neural network. The “deep-learning algorithm” started to burst in 2020 and continues till now, which indicated that this research topic has attracted continuous attention in recent years and would be the trend of research on AI application in GC.ConclusionsResearch related to AI in gastric cancer is increasing exponentially. Current research hotspots focus on the application of AI in gastric cancer, represented by convolutional neural networks and deep learning, in diagnosis and differential diagnosis and staging. Considering the great potential and clinical application prospects, the related area of AI applications in gastric cancer will remain a research hotspot in the future.

ObjectiveThis study aimed to evaluate the current research hotspots and development tendency of Transcranial Direct Current Stimulation (tDCS) in the field of neurobiology from a bibliometric perspective by providing visualized information to scientists and clinicians.Materials and methodsPublications related to tDCS published between 2000 and 2022 were retrieved from the Web of Science Core Collection (WOSCC) on May 5, 2022. Bibliometric features including the number of publications and citations, citation frequency, H-index, journal impact factors, and journal citation reports were summarized using Microsoft Office Excel. Co-authorship, citation, co-citation, and co-occurrence analyses among countries, institutions, authors, co-authors, journals, publications, references, and keywords were analyzed and visualized using CiteSpace (version 6.1.R3).ResultsA total of 4,756 publications on tDCS fulfilled the criteria we designed and then were extracted from the WOSCC. The United States (1,190 publications, 25.02%) and Harvard University (185 publications, 3.89%) were the leading contributors among all the countries and institutions, respectively. NITSCHE MA and FREGNI F, two key researchers, have made great achievements in tDCS. Brain Stimulation (306 publications) had the highest number of publications relevant to tDCS and the highest number of citations (4,042 times). In terms of potential hotspots, we observed through reference co-citation analysis timeline viewer related to tDCS that “depression”#0, “Sensorimotor network”#10, “working memory”#11, and “Transcranial magnetic stimulation”#9 might be the future research hotspots, while keywords with the strong burst and still ongoing were “intensity” (2018–2022), “impairment” (2020–2022), “efficacy” (2020–2022), and “guideline” (2020–2022).ConclusionThis was the first-ever study of peer-reviewed publications relative to tDCS using several scientometric and visual analytic methods to quantitatively and qualitatively reveal the current research status and trends in the field of tDCS. Through the bibliometric method, we gained an in-depth understanding of the current research status and development trend on tDCS. Our research and analysis results might provide some practical sources for academic scholars and clinicians.

Background and aimPyroptosis is an inflammatory form of programmed cell death implicated in inflammation and disease. Moreover, inducing pyroptosis has been appreciated as anti-cancer therapy for its ability to unleash anti-cancer immune responses.MethodsUtilizing the data available in The Cancer Genome Atlas (TCGA), pyroptosis-related genes’ (PRGs) expression, genomic aberrations, and clinical significance were systematically analyzed in pan-cancer. A GSVA score was obtained to rate pyroptosis level and divide the cancers into pyroptosis-low and pyroptosis-high groups. Immunohistochemistry (IHC) was used to evaluate the differential expression of major PRGs (GSDMC, GSDMD, GSDME, NLRP3, NLRC4, IL1B) in selected tumor types (COAD, HNSC, KIRC, LIHC, LUAD, LUSC). Selection of tumors for immunohistochemistry (IHC) was based on their expression pattern in TCGA cancers, clinical relevance, tumor epidemiology, and sample availability.ResultsDifferential expression of PRGs was evident in various cancers and associated with prognosis which was driven by genomic variations and epigenetic abnormalities, such as single nucleotide variations (SNVs), copy number variation (CNV) and DNA methylation level. For example, methylation of PRGs in lower grade glioma (LGG), uveal melanoma (UVM) and kidney renal clear cell carcinoma (KIRC) were predictive of improved survival as upregulation of PRGs was risky in these cancers. Pyroptosis level significantly differentiated tumor from normal samples in 15 types of cancers, exhibited a progressive trend with cancer stage, observed variation among cancer subtypes, and showed a significant association with cancer prognosis. Higher pyroptosis level was associated with worst prognosis in majority of the cancers in terms of OS (KIRC, LGG, and UVM), PFS (GBM, KIRC, LGG, PRAD, THCA, and THYM) and DSS (KIRC and LGG) as estimated by Kaplan-Meier survival curves. Moreover, Pyroptosis level was strongly indicative of a hot tumor immune microenvironment with high presence of CD8+ T cell and other T cell subtypes. Several oncogenic pathways, such as P53 pathway, DNA repair, KRAS signaling, epithelial-mesenchymal transition (EMT), IL6 JAK STAT3 signaling, IL2 STAT5 signaling, PI3K AKT MTOR signaling and angiogenesis, were enriched in pyroptosis-hi subgroups across cancers.ConclusionsGenetic alterations in PRGs greatly influence the pyroptosis level and cancer prognosis. A relatively hot tumor immune microenvironment was associated with pyroptosis irrespective of the cancer prognosis. Overall, our study reveals the critical role of pyroptosis in cancer and highlights pyroptosis-based therapeutic vulnerabilities.