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The addition of biogas liquid is a practical way to improve the yield of biological coalbed methane. The microbial composition in biogas liquid is complex, and whether it could participate in the sulfur conversion of coal remains unknown. In this study, sulfur conversion-related microbial communities were enriched from biogas liquid, which was dominated by genera Anaerosolibacter, Bacillus, Hydrogenispora, and Oxobacter. The co-culture of these groups with coal significantly changed the coal microbial community composition but did not increase the content of CH4 and H2S. The changed microbial communities mainly belonged to phyla Firmicutes, Proteobacteria, and Actinobacteriota, and increased the relative abundance of genera Bacillus, Thermicanus, Hydrogenispora, Oxobacter, Lutispora, Anaerovorax, Desulfurispora, Ruminiclostridium, and Fonticella. From the microscopic structure of coal, an increase in the number of holes and roughness on the surface of the coal was found but the change of surface functional groups was weak. In addition, the addition of S-related microbial communities increased the contents of phoxim, methylthiobenzoylglycine and glibornuride M5 in aromatic compounds, as well as the content of lauryl hydrogen sulfate in alkyl compounds. Furthermore, the dibenzothiophene degradation-related microbial communities included Bacillus, Brevibacillus, Brevundimonas, Burkholderia-Caballeronia-Paraburkholderia, and Thermicanus, which can break C-S bonds or disrupt benzene rings to degrade dibenzothiophene. In conclusion, the S-related microbial communities in biogas liquid could rebuild the coal microbial community and be involved in the conversion process of organic sulfur in coal.

Abstract Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Abstract Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein–protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.

Compound channels consisting of obvious riverbank beaches and deep grooves are widely found in the upper reaches of the Yangtze River, and the special and complex flow structure of compound channels has an important impact on fish habitats. Currently, there are insufficient studies on how the flow characteristics of compound channels affect the suitability of spawning habitats for fish. In this study, two different spawning types of fishes, namely, the Four major Chinese carps and the Schizothorax prenanti, were taken as representatives, and two different hydrodynamic effects, namely, the characteristic flow and the typical flow pulse process, were considered. Using the 3D hydrodynamic model and physical habitat suitability model, we investigated the spatio-temporal distribution characteristics of the habitat suitability indicator for representative fishes in a compound channel, and analyzed the impact of hydraulic characteristics of the compound channel on the suitability of spawning habitats for representative fish species. The results show that the suitable areas for spawning and habitat of the Four major Chinese carps are concentrated in the middle and upper layers of the flow field, with the distribution characteristics of locating in deep grooves under low flow and locating in riverbank beaches under high flow; the spawning and habitat suitability area for the Schizothorax prenanti is located mainly in the near-bottom flow field of the riverbank beach of the compound channel, and with the increase of the flow, the size of the suitable area in the riverbank beach decreases and migrates to the bank gradually. Under the effect of a high-flow pulse process in a certain flow interval, the ideal weighted usable area (IWUA) of habitat suitability indicator greater than 0.8 (HSI ≥ 0.8) for the Four major Chinese carps and Schizothorax prenanti will increase with the increase of flow, and the connectivity of ideal habitat patches will also be enhanced. The results of this study are of great significance for the conservation of river fish resources and ecological engineering construction, etc.

Summary: Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

Abstract Background This retrospective study was conducted to compare the safety and efficacy of Sun’s tip-flexible semirigid ureterorenoscopy (tf-URS), super-mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopy (FURS) in treating upper urinary tract calculi, including upper ureteral or renal calculi. Methods We included patients with upper ureteral calculi or renal calculi 1.0–2.0 cm in size, who underwent tf-URS, SMP or FURS, respectively. The indicators reflecting safety and efficacy were compared among the three surgical techniques. Results SMP presented with higher single stone crushing success rate, but longer operation time and postoperative hospital stay, more blood loss, and higher postoperative pain score compared with FURS and tf-URS (P 0.05). Conclusions tf-URS and FURS have the advantages in minimal invasion, hospitalization cost, patient comfort, and hospital stay while SMP has higher stone-free rate. These three surgical techniques are safe, reliable and complementary, which should be selected according to the actual situation.

Objectives: Acute aortic dissection (AAD) is an extremely life-threatening medical emergency, often misdiagnosed in its early stages, resulting in prolonged wait times for rescue. This study aims to identify potential serum biomarkers that can assist in the accurate diagnosis of AAD and effectively differentiate it from other conditions causing severe chest pain. Methods: A total of 122 patients with AAD and 129 patients with other severe chest pain disorders were included in the study. Serum samples were analyzed by measuring the peak intensities of Raman spectra. For each measurement, the Raman spectrum was accumulated by two accumulations (3 s per acquisition). Logistic regression and nomogram models were developed using these peak intensities as well as D-dimer levels to predict the occurrence of AAD. The clinical utilities of these models were assessed through receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) in both training and internal test cohorts. Results: The D-dimer levels of AAD patients were significantly increased, as well as higher intensities at specific Raman peaks, including 505 cm−1, 842 cm−1, 947 cm−1, 1254 cm−1, 1448 cm−1, and 1655 cm−1 when compared to non-AAD patients. Conversely, decreased intensities were observed at Raman peaks such as 750 cm−1, 1004 cm−1, 1153 cm−1, 1208 cm−1, and 1514 cm−1 in AAD patients. Least absolute shrinkage and selection operator regression analysis on the training cohort identified eight potential predictors: D-dimer along with intensity measurements at peaks such as 505 cm−1, 750 cm−1, 1153 cm−1, 1208 cm−1, 1254 cm−1, 1448 cm−1, and 1655 cm−1. The combination of these eight potential predictors demonstrated a good discriminatory performance, with an area under the curve (AUC) value of 0.928 in the training cohort and an AUC of 0.936 in the internal test cohort, outperforming the use of D-dimer alone. Furthermore, DCA curve analysis revealed that leveraging this combination of eight potential predictors would provide substantial net benefits for clinical application. Moreover, this combination significantly augmented discrimination power, as evidenced by a continuous NRI of 39.8 % and IDI of 9.95 % in the training cohort, as well as a continuous NRI of 27.1 % and IDI of 9.95 % in the internal test cohort. Conclusions: The employment of this combination of eight potential predictors effectively rules out AAD to a greater extent. This study presents a promising diagnostic strategy for early detection using optical diagnostic techniques such as Raman spectroscopy.

BackgroundAcute myeloid leukemia (AML) is a highly aggressive and pathogenic hematologic malignancy with consistently high mortality. Lysosomes are organelles involved in cell growth and metabolism that fuse to form specialized Auer rods in AML, and their role in AML has not been elucidated. This study aimed to identify AML subtypes centered on lysosome-related genes and to construct a prognostic model to guide individualized treatment of AML.MethodsGene expression data and clinical data from AML patients were downloaded from two high-throughput sequencing platforms. The 191 lysosomal signature genes were obtained from the database MsigDB. Lysosomal clusters were identified by unsupervised consensus clustering. The differences in molecular expression, biological processes, and the immune microenvironment among lysosomal clusters were subsequently analyzed. Based on the molecular expression differences between lysosomal clusters, lysosomal-related genes affecting AML prognosis were screened by univariate cox regression and multivariate cox regression analyses. Algorithms for LASSO regression analyses were employed to construct prognostic models. The risk factor distribution, KM survival curve, was applied to evaluate the survival distribution of the model. Time-dependent ROC curves, nomograms and calibration curves were used to evaluate the predictive performance of the prognostic models. TIDE scores and drug sensitivity analyses were used to explore the implication of the model for AML treatment.ResultsOur study identified two lysosomal clusters, cluster1 has longer survival time and stronger immune infiltration compared to cluster2. The differences in biological processes between the two lysosomal clusters are mainly manifested in the lysosomes, vesicles, immune cell function, and apoptosis. The prognostic model consisting of six prognosis-related genes was constructed. The prognostic model showed good predictive performance in all three data sets. Patients in the low-risk group survived significantly longer than those in the high-risk group and had higher immune infiltration and stronger response to immunotherapy. Patients in the high-risk group showed greater sensitivity to cytarabine, imatinib, and bortezomib, but lower sensitivity to ATRA compared to low -risk patients.ConclusionOur prognostic model based on lysosome-related genes can effectively predict the prognosis of AML patients and provide reference evidence for individualized immunotherapy and pharmacological chemotherapy for AML.

The high attrition rate of college counselors in Chinese colleges has evolved into a social problem that is receiving an increasing amount of attention. The current study aims to investigate the link between organizational justice and organizational commitment on turnover intention and whether this effect is mediated by job satisfaction, drawing upon the framework of Social Exchange Theory. Meanwhile, whether the relationship between organizational justice and turnover intention is moderated by job embeddedness based on the Job Embeddedness Theory. Data gathered from 161 college counselors in China were analyzed using a structural equation model. The results showed significant relationship between organizational justice, organizational commitment, and turnover intention. Furthermore, job embeddedness plays a moderating role in the relationship between job embeddedness and turnover intention; specifically, the higher the degree of job embeddedness, the weaker the effect of organizational justice on turnover intention. Most importantly, it is confirmed that job satisfaction partially mediates the link between organizational justice, organizational commitment, and turnover intention. These outcomes contribute valuable new knowledge that can be employed to improve counselor retention in colleges. Meanwhile, the findings are examined in detail, and recommendations for future studies are provided.

Abstract Objectives To explore the characteristics of myocardial involvement in Wilson Disease (WD) patients by cardiac magnetic resonance (CMR). Methods We prospectively included WD patients and age- and sex-matched healthy population. We applied CMR to analyze cardiac function, strain, T1 maps, T2 maps, extracellular volume fraction (ECV) maps, and LGE images. Subgroup analyzes were performed for patients with WD with predominantly neurologic manifestations (WD‐neuro +) or only hepatic manifestations (WD‐neuro −). Results Forty-one WD patients (age 27.9 ± 8.0 years) and 40 healthy controls (age 25.4 ± 2.9 years) were included in this study. Compared to controls, the T1, T2, and ECV values were significantly increased in the WD group (T1 1085.1 ± 39.1 vs. 1046.5 ± 33.1 ms, T2 54.2 ± 3.3 ms vs. 51.5 ± 2.6 ms, ECV 31.8 ± 3.6% vs. 24.3 ± 3.7%) (all p

This study utilizes a new approach for short-term stock correlation forecasting using a combination of convolutional neural networks (CNN), bi-directional long and short-term memory (BiLSTM), and attention mechanisms to address the issue of information loss due to excessively long input time series data. The objective is to improve the accuracy of short-term equity correlation forecasts, which is essential for the efficient management of financial asset portfolios. The existing time series models usually only take into account the effect of stock historical data characteristics on stock correlation but ignore the fact that stock correlation is affected by multiple factors and undergoes an unknown unstable trend. More efficient methods or algorithms need to be devised to deal with financial data. This paper explores stock metrics and introduces a multi-factor model to quantify the factors affecting stock returns in order to calculate the correlation between stocks. Meanwhile, to cope with the problem of incomplete input data, this paper simultaneously incorporates stock return data that is directly related to the correlation data. In the CNN-BiLSTM-Attention (CLATT) model, the role of the CNN module is to obtain high-dimensional features from the input time series data, and the role of the BiLSTM module is to process the time series information to capture the time-series features in the stock return data and correlation data in the sample. In order to acquire the inherent correlation between the input stock return data and correlation data and to enhance the prediction accuracy of the model, the attention mechanism is finally implemented and used to optimize the weights of the BiLSTM output. In this paper, mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE) metrics, mean absolute percentage of error (MAPE), and the coefficient of determination $R^{2}$ , as well as four benchmark models, are used to evaluate the performance of the proposed model. The result shows that the CLATT model has 57.32% and 33% improvement in the correlation prediction accuracy of different stock portfolios compared to the single LSTM model, and the model prediction accuracy has been improved. Compared with the benchmark CNN-BiLSTM, it also has 56.06% and 28.87% improvement.

AimsThe high salinity of soil, nutrient scarcity, and poor aggregate structure limit the exploitation and utilization of coastal mudflat resources and the sustainable development of saline soil agriculture. In this paper, the effects of applying exogenous organic acids combined with biological substrate on the composition and diversity of soil bacterial community were studied in moderately saline mudflats in Jiangsu Province.MethodsA combination of three exogenous organic acids (humic acid, fulvic acid, and citric acid) and four biological substrates (cottonseed hull, cow manure, grass charcoal, and pine needle) was set up set up on a coastal saline mudflat planted with a salt-tolerant forage grass, sweet sorghum. A total of 120 kg ha−1 of organic acids and 5,000 kg ha−1 of substrates were used, plus two treatments, CK without application of organic acids and substrates and CK0 in bare ground, for a total of 14 treatments.ResultsNo significant difference was found in the alpha diversity of soil bacterial community among all treatments (p ≥ 0.05), with the fulvic acid composite pine needle (FPN) treatment showing the largest increase in each index. The beta diversity differed significantly (p

Aims Turbulent aortic flow makes the cardiovascular system less effective. It remains unknown if patients with heart failure with preserved ejection fraction (HFpEF) have disturbed aortic flow. This study sought to investigate advanced markers of aortic flow disturbances in HFpEF. Methods This case-controlled observational study used four-dimensional flow cardiovascular magnetic resonance derived, two-dimensional phase-contrast reformatted plane data at an orthogonal plane just above the sino-tubular junction. We recruited 10 young healthy controls (HCs), 10 old HCs and 23 patients with HFpEF. We analysed average systolic aortic flow displacement (FDsavg), systolic flow reversal ratio (sFRR) and pulse wave velocity (PWV). In a sub-group analysis, we compared old HCs versus age-gender-matched HFpEF (N=10). Results Differences were significant in mean age (P 17.7% achieved 74% sensitivity, 70% specificity for differentiating them. sFRR was notably higher in HFpEF (11±10% vs 7±6%, P 7.3% yielded 78% sensitivity, 70% specificity in differentiating these groups. In sub-group analysis, FDsavg remained distinctly elevated in HFpEF (22.4±9.7% vs 16±4.9%, P=0.029). FDsavg of >16% showed 100% sensitivity and 70% specificity (P=0.01). Similarly, sFRR remained significantly higher in HFpEF (11.3±9.5% vs 6.6±6.4%, P=0.007). A sFRR of >7.2% showed 100% sensitivity and 60% specificity (P

Purpose The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root.Methods This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC.Results For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p

BackgroundPulmonary artery (PA) strain is associated with structural and functional alterations of the vessel and is an independent predictor of cardiovascular events. The relationship of PA strain to metabolomics in participants without cardiovascular disease is unknown.MethodsIn the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling. PA global longitudinal strain (GLS) analysis was performed by tracking the change in distance from the PA bifurcation to the pulmonary annular centroid, using standard cine CMR images. Circulating metabolites were measured by cross-sectional targeted metabolomics analysis.ResultsAmong n = 170 adults (mean age 71 ± 6.3 years old; 79 women), mean values of PA GLS were 16.2 ± 4.4%. PA GLS was significantly associated with age (β = −0.13, P = 0.017), heart rate (β = −0.08, P = 0.001), dyslipidemia (β = −2.37, P = 0.005), and cardiovascular risk factors (β = −2.49, P = 0.001). Alanine (β = −0.007, P = 0.01) and proline (β = −0.0009, P = 0.042) were significantly associated with PA GLS after adjustment for clinical risk factors. Medium and long-chain acylcarnitines were significantly associated with PA GLS (C12, P = 0.027; C12-OH/C10-DC, P = 0.018; C14:2, P = 0.036; C14:1, P = 0.006; C14, P = 0.006; C14-OH/C12-DC, P = 0.027; C16:3, P = 0.019; C16:2, P = 0.006; C16:1, P = 0.001; C16:2-OH, P = 0.016; C16:1-OH/C14:1-DC, P = 0.028; C18:1-OH/C16:1-DC, P = 0.032).ConclusionBy conventional CMR, PA GLS was associated with aging and vascular risk factors among a contemporary cohort of older adults. Metabolic pathways involved in PA stiffness may include gluconeogenesis, collagen synthesis, and fatty acid oxidation.

Abstract Background Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. Methods We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. Results Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = − 0.355 for LV and − 0.318 for RV), and KEiEDV E/A ratio (r = − 0.475 for LV and − 0.504 for RV) decreased significantly, with age. Conclusion These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Introduction Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. Methods A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. Results Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend

Urbanization is rapidly occupying green spaces, making it crucial to understand implicit conflicts between urbanization and greenness. This study proposes an ecological greenness index (EGI) and a comprehensive urbanization index (CUI) and selects Nanjing, a megacity in China, as the study area to research the spatial and temporal evolutionary trends of the EGI and CUI in the context of land use/land cover (LULC) changes from 2000 to 2020. Meanwhile, the conflicts and complex interaction characteristics of the EGI and CUI are discussed from both static and dynamic perspectives, and their driving mechanisms are investigated by combining specific indicators. The results demonstrate that over the past 20 years, LULC in Nanjing was dominated by cultivated land, forest land, and artificial surfaces. The encroachment of artificial surfaces on green space was strengthened, resulting in a decrease in the proportion of cultivated land from 70.09% in 2000 to 58.00% in 2020. The CUI increased at a change rate of 0.6%/year, while the EGI showed significant browning (change rate: −0.23%/year), mainly concentrated within the main urban boundaries. The relationship between the CUI and EGI made the leap from “primary coordination” to “moderate coordination”, but there remains a risk of further deterioration of the decoupling relationship between the CUI and ecological pressures. The multi-year average contribution of the CUI to the EGI was 49.45%. Urbanization activities that dominate changes in greenness have changed over time, reflecting the timing of urban conflict management. The results provide important insights for urban ecological health monitoring and management.

In the traditional farming systems, the excessive application of chemical fertilizers to boost crop yields has resulted in a range of issues, such as soil quality degradation, soil structure deterioration, and pollution of the farmland ecological environment. Green manure, as a high-quality biological fertilizer source with rich nutrient content, is of great significance for enhancing the soil quality and establishing a healthy farmland ecosystem. However, there are few studies on the effects of different green manures on the soil nutrient levels, enzyme activities, and soil bacterial community composition in the rice–wheat rotation areas in southern China. Thus, we planted Chinese milk vetch (MV; Astragalus sinicus L.), light leaf vetch (LV; Vicia villosa var.), common vetch (CV; Vicia sativa L.), crimson clover (CC; Trifolium incarnatum L.), Italian ryegrass (RG; Lolium multiflorum L.), and winter fields without any crops as a control in the Taihu Lake area of Jiangsu. The soil samples collected after tilling and returning the green manure to the field during the bloom period were used to analyze the effects of the different green manures on the soil nutrient content, enzyme activity, and the structural composition of the bacterial community. This analysis was conducted using chemical methods and high-throughput sequencing technology. The results showed that the green manure returned to the field increased the soil pH, soil organic matter (SOM), alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), available potassium (AK), sucrose (SC), urease (UE), and neutral phosphatase (NEP) contents compared to the control. They increased by 1.55% to 10.06%, 0.26% to 9.31%, 20.95% to 28.42%, 20.66% to 57.79%, 12.38% to 37.94%, 3.11% to 58.19%, 6.49% to 32.99%, and 50.0% to 80.36%, respectively. In addition, the green manure field increased the relative abundance of the genera Proteobacteria and Haliangium while decreasing the relative abundance of Gemmatimonadetes, Chloroflexi, SBR1031, and Anaeromyxobacter in the soil bacteria. Both the number of ASVs (amplicon sequence variants) and α-diversity of the soil bacterial communities were higher compared to the control, and the β-diversity varied significantly among the treatments. Alkali-hydrolyzed nitrogen and neutral phosphatase had the greatest influence on the soil bacterial community diversity, with alkali-hydrolyzed nitrogen being the primary soil factor affecting the soil bacterial community composition. Meanwhile, the results of the principal component analysis showed that the MV treatment had the most significant impact on soil improvement. Our study provides significant insights into the sustainable management of the soil quality in rice–wheat rotations. It identifies MV as the best choice among the green manure crops for improving the soil quality, offering innovative solutions for reducing chemical fertilizer dependence and promoting ecological sustainability.

As the sheep industry rapidly moves towards modernization, digitization, and intelligence, there is a need to build breeding farms integrated with big data. By collecting individual information on sheep, precision breeding can be conducted to improve breeding efficiency, reduce costs, and promote healthy breeding practices. In this context, the accurate identification of individual sheep is essential for establishing digitized sheep farms and precision animal husbandry. Currently, scholars utilize deep learning technology to construct recognition models, learning the biological features of sheep faces to achieve accurate identification. However, existing research methods are limited to pattern recognition at the image level, leading to a lack of diversity in recognition methods. Therefore, this study focuses on the small-tailed Han sheep and develops a sheep face recognition method based on three-dimensional reconstruction technology and feature point matching, aiming to enrich the theoretical research of sheep face recognition technology. The specific recognition approach is as follows: full-angle sheep face images of experimental sheep are collected, and corresponding three-dimensional sheep face models are generated using three-dimensional reconstruction technology, further obtaining three-dimensional sheep face images from three different perspectives. Additionally, this study developed a sheep face orientation recognition algorithm called the sheep face orientation recognition algorithm (SFORA). The SFORA incorporates the ECA mechanism to further enhance recognition performance. Ultimately, the SFORA has a model size of only 5.3 MB, with accuracy and F1 score reaching 99.6% and 99.5%, respectively. During the recognition task, the SFORA is first used for sheep face orientation recognition, followed by matching the recognition image with the corresponding three-dimensional sheep face image based on the established SuperGlue feature-matching algorithm, ultimately outputting the recognition result. Experimental results indicate that when the confidence threshold is set to 0.4, SuperGlue achieves the best matching performance, with matching accuracies for the front, left, and right faces reaching 96.0%, 94.2%, and 96.3%, respectively. This study enriches the theoretical research on sheep face recognition technology and provides technical support.

Abstract Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 ‘4D Flow CMR Consensus Statement’. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Abstract Background Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context. Objective whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug. Design a randomized, double-blind, parallel, multi-center clinical trial. Setting five university medical centers and three teaching hospitals in China. Participants patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia. Intervention patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg–1, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg–1, respectively), and a 10-min lockout time. Outcomes the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score

Intestinal parasites, such as Eimeria, are common among plateau pika (Ochotona curzoniae). The gut microbiome is an essential driver of the host response to gastrointestinal parasites. However, the effects of intestinal protozoal parasites on the temporal variations in the gut microbiome and behavioral and physiological activities remain unknown. Our study conducted treatments involving experimental feeding of pika with Eimeria oocysts or anticoccidia under laboratory conditions to focus on the parasite-associated alterations in gut bacterial communities, host behavioral activity, physiology, and host–bacteria relationships. The results showed insignificant differences in bacterial community structures among treatments on the basis of Bray–Curtis distance metrics, whereas the patterns of temporal alterations in the bacterial communities were changed by the treatments. Bacterial alpha diversities did not vary with the treatments, and experimental feeding with Eimeria slowed down the decrement rate of alpha diversity. Furthermore, few bacterial members were significantly changed by the treatments—only the genus Ruminococcus and the species Ruminococcus flavefaciens, which were associated with energy metabolism. Experimental feeding with Eimeria modified the temporal variations in the bacterial members, including a lower loss rate of the relative abundance of the dominant families Muribaculaceae and Ruminococcaceae in the group with Eimeria experimental feeding. Moreover, a shifting energy trade-off was suggested by the parasite-induced increments in thyroid hormones (triiodothyronine and tetraiodothyronine) and decrements in exploration behavior in the group with Eimeria feeding. However, we did not detect specific connections between gut bacterial communities and pika behaviors and physiology in terms of energy trade-offs. Further in-depth research is needed to examine the role of Eimeria-modified differences in the gut bacteria of plateau pika.

ABSTRACTBackground miR-454-3p is considered to have a crucial role in cancer progression, but the potential involvement in acute myeloid leukemia (AML) remains unclear.Methods Expression of miR-454-3p and ZEB2 mRNA and protein were quantified in AML cell lines. Cells were transfected with miR-454-3p inhibitor or mimic and cell growth was assessed by colony formation and CCK-8 assays and the cell cycle, apoptosis and autophagy were investigated by Western blotting, flow cytometry, immunofluorescence and 3-methyladenine (3-MA) treatment.Results miR-454-3p expression was attenuated in AML cells. miR-454-3p overexpression attenuated cell growth and stimulated cell cycle arrest, apoptosis and autophagy. Dual-luciferase reporter assays and bioinformatics analysis showed that AML progression was inhibited when miR-454-3p regulated ZEB2, an effect confirmed by rescue assays. 3-MA reduced the autophagy-inducing effect of ZEB2 knockdown and indicated that autophagy induced apoptosis. miR-454-3p downregulated p-mTOR/p-AKT levels in AML cells.Conclusion The novel role of miR-454-3p as a tumor inhibitor in AML via regulation of the ZEB2/AKT/mTOR axis was demonstrated, indicating miR-454-3p as a potential new molecular target for AML.

Aims Blood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data.Methods In this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals.Results Age and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002.Conclusion CMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters.

The rapid growth of industrialization and urbanization in China has led to an increase in soil heavy metal pollution, which poses a serious threat to ecosystem safety and human health. The advancement of spectral technology offers a way to rapidly and non-destructively monitor soil heavy metal content. In order to explore the potential of rice leaf spectra to indirectly estimate soil heavy metal content. We collected farmland soil samples and measured rice leaf spectra in Xushe Town, Yixing City, Jiangsu Province, China. In the laboratory, the heavy metals Cd and As were determined. In order to establish an estimation model between the pre-processed spectra and the soil heavy metals Cd and As content, a genetic algorithm (GA) was used to optimise the partial least squares regression (PLSR). The model’s accuracy was evaluated and the best estimation model was obtained. The results showed that spectral pre-processing techniques can extract hidden information from the spectra. The first-order derivative of absorbance was more effective in extracting spectral sensitive information from rice leaf spectra. The GA-PLSR model selects only about 10% of the bands and has better accuracy in spectral modeling than the PLSR model. The spectral reflectance of rice leaves has the capacity to estimate Cd content in the soil (relative percent difference [RPD] = 2.09) and a good capacity to estimate As content in the soil (RPD = 2.97). Therefore, the content of the heavy metals Cd and As in the soil can be estimated indirectly from the spectral data of rice leaves. This study provides a reference for future remote sensing monitoring of soil heavy metal pollution in farmland that is quantitative, dynamic, and non-destructive over a large area.

Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco. According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes (ZO-1, Occludin, Claudin-1) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes (TNF, IL-1β, IL-8, IL-10). In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.

Abstract Background Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. Methods PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. Results 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P

Abstract Background Implementation of physical activity strategies in older populations may be influenced by underlying psychosocial and gender-based factors to physical activity. We explored associations between these factors and physical activity behaviors and technology among older men and women. Methods Community older adults underwent echocardiography and interviewer administered questionnaires that collected physical activity habits, self-motivation, self-empowerment and smartphone usage patterns associated with physical activity. Aerobic capacity was denoted by VO2max (High VO2 was defined as VO2 > 35 (ml/kg/min) for men or VO2 > 27 (ml/kg/min) for women). Results Among 180 participants (mean age 77 (71–80) years; 43% females), 101 (56.1%) had a low VO2max. Barriers to activity were lack of time (27.8%), tiredness (26.7%), affordability (12.8%) and pain while exercising (12.2%). Compared to participants with high VO2max, those with low VO2max were less likely to report feeling good post-exercise (70.3% vs 86.1%, adjusted p = 0.041) and express barriers to exercise (72.3% vs 88.6%, adjusted p = 0.017). Compared to men, women were more likely to express motivation for exercise if they were guided by an instructor (20.5% vs 1.96%, adjusted p = 0.027), less likely to prefer control over exercise type and difficulty (57.7% vs 82.4%, adjusted p = 0.001), express interest in smartphone apps (7.84% vs 24.4%, adjusted p = 0.01) and participate in apps-guided exercise (10.3% vs 29.4%, adjusted p = 0.001). Major factors that motivated the use of smartphone applications to manage individual health were financial incentives (23.9%) and guidance on exercise routines (21.1%) while the reveal of personal information was a major deterrent (28.3%). Conclusions We observed differences in physical activity motivation, empowerment and technology use based on gender and functional status. Tailoring physical activity strategies, including digital health strategies, that target psychosocial and gender-based factors may improve activity participation in older adults.

Abstract Background DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3AR882) in acute myeloid leukemia (AML). AML patients with DNMT3A R882 mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it is urgent to investigate daunorubicin resistance in AML patients with DNMT3A R882 mutant. Method AML cell lines with DNMT3A-wild type (DNMT3A-WT), and DNMT3A-Arg882His (DNMT3A-R882H) mutation were constructed to investigate the role of DNMT3A R882H mutation on cell proliferation, apoptosis and cells’ sensitivity to Danunorubin. Bioinformatics was used to analyze the role of nuclear factor-E2-related factor (NRF2) in AML patients with DNMT3A R882 mutation. The regulatory mechanism of DNMT3A R882H mutation on NRF2 was studied by Bisulfite Sequencing and CO-IP. NRF2 inhibitor Brusatol (Bru) was used to explore the role of NRF2 in AML cells carried DNMT3A R882H mutation. Results AML cells with a DNMT3A R882H mutation showed high proliferative and anti-apoptotic activities. In addition, mutant cells were less sensitive to daunorubicin and had a higher NRF2 expression compared with those in WT cells. Furthermore, the NRF2/NQO1 pathway was activated in mutant cells in response to daunorubicin treatment. DNMT3A R882H mutation regulated the expression of NRF2 via influencing protein stability rather than decreasing methylation of NRF2 promoter. Also, NRF2/NQO1 pathway inhibition improved mutant cells’ sensitivity to daunorubicin significantly. Conclusion Our findings identified NRF2 as an important player in the regulation of cell apoptosis through which helps mediate chemoresistance to daunorubicin in AML cells with DNMT3A R882H mutation. Targeting NRF2 might be a novel therapeutic approach to treat AML patients with a DNMT3A R882H mutation. Video abstract

Abstract Background To validate the k-adaptive-t autocalibrating reconstruction for Cartesian sampling (kat-ARC), an exclusive sparse reconstruction technique for four-dimensional (4D) flow cardiac magnetic resonance (CMR) using conservation of mass principle applied to transvalvular flow. Methods This observational retrospective study (2020/21-075) was approved by the local ethics committee at the University of East Anglia. Consent was waived. Thirty-five patients who had a clinical CMR scan were included. CMR protocol included cine and 4D flow using Kat-ARC acceleration factor 6. No respiratory navigation was applied. For validation, the agreement between mitral net flow (MNF) and the aortic net flow (ANF) was investigated. Additionally, we checked the agreement between peak aortic valve velocity derived by 4D flow and that derived by continuous-wave Doppler echocardiography in 20 patients. Results The median age of our patient population was 63 years (interquartile range [IQR] 54–73), and 18/35 (51%) were male. Seventeen (49%) patients had mitral regurgitation, and seven (20%) patients had aortic regurgitation. Mean acquisition time was 8 ± 4 min. MNF and ANF were comparable: 60 mL (51−78) versus 63 mL (57−77), p = 0.310). There was an association between MNF and ANF (rho = 0.58, p < 0.001). Peak aortic valve velocity by Doppler and 4D flow were comparable (1.40 m/s, [1.30−1.75] versus 1.46 m/s [1.25−2.11], p = 0.602) and also correlated with each other (rho = 0.77, p < 0.001). Conclusions Kat-ARC accelerated 4D flow CMR quantified transvalvular flow in accordance with the conservation of mass principle and is primed for clinical translation.

Abstract Background Laparoscopic-assisted repairs for pediatric inguinal hernia have gained gradual acceptance over the past decade. However, consensus about the optimal management is still lacking. The aim of this study is to compare outcomes of a modified laparoscope-assisted single-needle laparoscopic percutaneous extraperitoneal closure (LPEC) versus open repair of pediatric hernias/hydrocele in a single institution. Materials and methods We retrospectively reviewed the medical data of children who underwent laparoscope-assisted single-needle LPEC and open repair (OR) for inguinal hernia from 2014 to 2019. Data collection included demographics, laterality of hernia, surgical time and time to follow-up. We also reviewed and analyzed the evidence of recurrence, the incidence of metachronous contralateral inguinal hernia (MCIH), and other complications. Results In our cohort, 961 patients in the OR group and 1098 patients in the LPEC group were analyzed retrospectively. Mean operative time was significantly shorter in the LPEC group (22.3 ± 3.5 min) than in the OR group (27.8 ± 5.9 min) for bilateral hernia repair (p

Objective The current study aimed to perform whole-genome resequencing of Chinese indigenous Mongolian sheep breeds including Ujimqin, Sunit, and Wu Ranke sheep breeds (UJMQ, SNT, WRK) and deeply analyze genetic variation, population structure, domestication, and selection for domestication traits among these Mongolian sheep breeds. Methods Blood samples were collected from a total of 60 individuals comprising 20 WRK, 20 UJMQ, and 20 SNT. For genome sequencing, about 1.5 μg of genomic DNA was used for library construction with an insert size of about 350 bp. Pair-end sequencing were performed on Illumina NovaSeq platform, with the read length of 150 bp at each end. We then investigated the domestication and signatures of selection in these sheep breeds. Results According to the population and demographic analyses, WRK and SNT populations were very similar, which were different from UJMQ populations. Genome wide association study identified 468 and 779 significant loci from SNT vs UJMQ, and UJMQ vs WRK, respectively. However, only 3 loci were identified from SNT vs WRK. Genomic comparison and selective sweep analysis among these sheep breeds suggested that genes associated with regulation of secretion, metabolic pathways including estrogen metabolism and amino acid metabolism, and neuron development have undergone strong selection during domestication. Conclusion Our findings will facilitate the understanding of Chinese indigenous Mongolian sheep breeds domestication and selection for complex traits and provide a valuable genomic resource for future studies of sheep and other domestic animal breeding.

Abstract Oral submucous fibrosis (OSF) is a chronic and insidious oral potentially malignant disorder associated with a 4–17% risk of oral squamous cell carcinoma (OSCC). Our previous study found that proteasomal activator 28 gamma (PA28γ) is frequently overexpressed in oral squamous cell carcinoma and negatively correlated with poor patient prognosis. However, the role of PA28γ in the occurrence and development of OSF remains unclear. Here, we screened PA28γ-related genes and investigated their function in OSF. We demonstrated that the expression of PA28γ was positively associated with MEK1 and gradually elevated from normal to progressive stages of OSF tissue. Arecoline, a pathogenic component of OSF, could upregulate the protein levels of PA28γ and phosphorylated MEK1 and contribute to epithelial to mesenchymal transition (EMT) in epithelial cells. Notably, PA28γ could interact with MEK1 and upregulate its phosphorylation level. Furthermore, arecoline upregulated BRAF, which can interact with PA28γ and upregulate its protein level. Additionally, BRAF, PA28γ, and MEK1 could form protein complexes and then enhance the MEK1/ERK signaling pathways. The concrete mechanism of the protein stability of PA28γ is that BRAF mediates its degradation by inhibiting its ubiquitination. These findings underscore the instrumental role of PA28γ in the BRAF/MEK1 pathway and enhanced EMT through MEK1/ERK activation in OSF.

Background: The reproducibility of mitral regurgitation (MR) quantification by cardiovascular magnetic resonance (CMR) imaging using different software solutions remains unclear. This research aimed to investigate the reproducibility of MR quantification between two software solutions: MASS (version 2019 EXP, LUMC, Netherlands) and CAAS (version 5.2, Pie Medical Imaging). Methods: CMR data of 35 patients with MR (12 primary MR, 13 mitral valve repair/replacement, and ten secondary MR) was used. Four methods of MR volume quantification were studied, including two 4D-flow CMR methods (MRMVAV and MRJet) and two non-4D-flow techniques (MRStandard and MRLVRV). We conducted within-software and inter-software correlation and agreement analyses. Results: All methods demonstrated significant correlation between the two software solutions: MRStandard (r=0.92, p

Abstract The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

IntroductionOral lichen planus (OLP) is a common chronic inflammatory disorder of the oral mucosa with an unclear etiology. Several types of immune cells are involved in the pathogenesis of OLP.MethodsWe used single-cell RNA sequencing and immune repertoire sequencing to characterize the mucosal immune microenvironment of OLP. The presence of tissue-resident memory CD8+ T cells are validated by multiplex immunofluorescence.ResultsWe generated a transcriptome atlas from four OLP biopsy samples and their paired peripheral blood mononuclear cells (PBMCs), and compared them with two healthy tissues and three healthy PBMCs samples. Our analysis revealed activated tissue-resident memory CD8+ T cells in OLP tissues. T cell receptor repertoires displayed apperant clonal expansion and preferrential gene pairing in OLP patients. Additionally, obvious BCR clonal expansion was observed in OLP lesions. Plasmacytoid dendritic cells, a subtype that can promote dendritic cell maturation and enhance lymphocyte cytotoxicity, were identified in OLP. Conventional dendritic cells and macrophages are also found to exhibit pro-inflammatory activity in OLP. Cell-cell communication analysis reveals that fibroblasts might promote the recruitment and extravasation of immune cells into connective tissue.DiscussionOur study provides insights into the immune ecosystem of OLP, serving as a valuable resource for precision diagnosis and therapy of OLP.

Abstract Objective Doppler echocardiographic aortic valve peak velocity and peak pressure gradient assessment across the aortic valve (AV) is the mainstay for diagnosing aortic stenosis. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) is emerging as a valuable diagnostic tool for estimating the peak pressure drop across the aortic valve, but assessment remains cumbersome. We aimed to validate a novel semi-automated pipeline 4D flow CMR method of assessing peak aortic value pressure gradient (AVPG) using the commercially available software solution, CAAS MR Solutions, against invasive angiographic methods. Results We enrolled 11 patients with severe AS on echocardiography from the EurValve programme. All patients had pre-intervention doppler echocardiography, invasive cardiac catheterisation with peak pressure drop assessment across the AV and 4D flow CMR. The peak AVPG was 51.9 ± 35.2 mmHg using the invasive pressure drop method and 52.2 ± 29.2 mmHg for the 4D flow CMR method (semi-automated pipeline), with good correlation between the two methods (r = 0.70, p = 0.017). Assessment of AVPG by 4D flow CMR using the novel semi-automated pipeline method shows excellent agreement to invasive assessment when compared to doppler-based methods and advocate for its use as complementary to echocardiography.

With the rapid development of China’s industrialization and urbanization, the problem of heavy metal pollution in soil has become increasingly prominent, seriously threatening the safety of the ecosystem and human health. The development of hyperspectral remote sensing technology provides the possibility to achieve the rapid and non-destructive monitoring of soil heavy metal contents. This study aimed to fully explore the potential of ground and satellite image spectra in estimating soil heavy metal contents. We chose Xushe Town, Yixing City, Jiangsu Province as the research area, collected soil samples from farmland over two different periods, and measured the contents of the heavy metals Cd and As in the laboratory. At the same time, under field conditions, we also measured the spectra of wheat leaves and obtained HuanJing-1A HyperSpectral Imager (HJ-1A HSI) satellite image data. We first performed various spectral transformation pre-processing techniques on the leaf and image spectral data. Then, we used genetic algorithm (GA) optimized partial least squares regression (PLSR) to establish an estimation model of the soil heavy metal Cd and As contents, while evaluating the accuracy of the model. Finally, we obtained the best ground and satellite remote sensing estimation models and drew spatial distribution maps of the soil Cd and As contents in the study area. The results showed the following: (1) spectral pre-processing techniques can highlight some hidden information in the spectra, including mathematical transformations such as differentiation; (2) in ground and satellite spectral modeling, the GA-PLSR model has higher accuracy than PLSR, and using a GA for spectral band selection can improve the model’s accuracy and stability; (3) wheat leaf spectra provide a good ability to estimate soil Cd (relative percent difference (RPD) = 2.72) and excellent ability to estimate soil As (RPD = 3.25); HJ-1A HSI image spectra only provide the possibility of distinguishing high and low values of soil Cd and As (RPD = 1.87, RPD = 1.91). Therefore, it is possible to indirectly estimate soil heavy metal Cd and As contents using wheat leaf hyperspectral data, and HJ-1A HSI image spectra can also identify areas of key pollution.

Abstract Background Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. Methods Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. Results In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P

During the last two decades, numerous studies have shown the effects of traffic noise on animal vocal communication. However, studies on the influences of traffic noise on wildlife behavior and physiology are scarce. In the present study, we experimentally manipulated the traffic noise exposure of plateau pika, a native small mammal widely distributed in the alpine meadow of Qinghai-Tibet Plateau, to explore the effects of traffic noise exposure on its behavior and physiology. We showed that noise exposure increased the pika’s exploration and cortisol concentration (CORT) but decreased the resting metabolic rate (RMR). In addition, the relationships between RMR and exploration or CORT appeared under traffic noise treatment. This study suggests that traffic noise plays a large role in the behavior and physiology of plateau pikas and may have a long-term negative effect on the fitness of rodent populations. Generalizing these non-lethal effects to different taxa is crucial for the conservation and management of biodiversity in this increasingly noisy world.

Abstract Background X‐linked cone‐rod dystrophy (CORDX) is one form of inherited retinal disorders (IRDs) characterized by progressive dysfunction of photoreceptor. Three types of CORDX were reported and CACNA1F gene defect can cause CORDX3. The aim of this study was to investigate the pathogenic variant in a Chinese family with IRD. Methods The two affected subjects including the proband and his elder sister underwent ophthalmic examinations. Whole exome sequencing (WES) was performed in the proband at first, then co‐segregation analysis was performed in the family by Sanger sequencing. Minigene approach was used to verify the effect of the mutation on the splicing of CACNA1F. X‐chromosomal inactivation assay was performed to evaluate the inactivation patterns of the female carriers. Results The ophthalmic examination results of the proband fit the clinical description of CORDX3, and the female patient presented with only mild symptoms due to mildly skewed X‐chromosomal inactivation (ratio 67: 33). Molecular genetic testing identified a novel splice‐site mutation c.3847‐2A > G in CACNA1F (NM_005183.4) gene in the patients, which inherited from their asymptomatic mother. Minigene approach confirmed that c.3847‐2A > G could affect the splicing of CACNA1F. Conclusion Our study identified a novel splice‐site mutation in the CACNA1F gene, which expanded the mutational spectrum of CACNA1F‐releated diseases and demonstrated the importance of combining clinical and genetic testing in the diagnosis of IRDs.

Abstract Background Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. Methods In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8–24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. Results PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p

The Yersinia outer protein J (YopJ) family of effectors, which are present in many plant and animal pathogens are non-canonical acetyltransferases that are activated by the eukaryote-specific cofactor inositol hexaphosphate (InsP6). Here, the authors combine X-ray crystallography, biochemical and functional analyses to characterise the structure and activation mechanism of the YopJ family effector PopP2 from the plant pathogen Ralstonia solanacearum and observe that InsP6 binding induces major conformational changes in PopP2 with a helix-to-strand fold-switching in its catalytic core.

Abstract Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene regulation. The most abundant modification of mRNA, N 6-methyladenosine (m6A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m6A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m6A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m6A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Abstract The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been considered to be crucial in tumor malignancy. Although CRNDE is highly expressed in acute myeloid leukemia (AML), its mechanism of action remains unknown. In this study, GEPIA and qRT-PCR were performed to confirm the expression of CRNDE in AML samples and cell lines, respectively. CRNDE shRNA vectors were transfected to explore the biological functions of CRNDE. The cell proliferation was assessed by the CCK8 assay, while apoptosis and cell cycle distribution were measured by flow cytometry and Western blotting. The results showed that CRNDE was overexpressed in both AML samples and cell lines. CRNDE silencing inhibited proliferation and increased apoptotic rate and cell cycle arrest of KG-1a cells. The luciferase reporter assay coupled with RIP assay revealed that CRNDE act as a ceRNA. Rescue assays demonstrated that the effects of CRNDE silencing could be reversed by miR-136-5p inhibitors. In conclusion, our results expound that the CRNDE/miR-136-5p/MCM5 axis modulates cell progression and provide a new regulatory network of CRNDE in KG-1a cells.

This research aimed to recover anthocyanin-rich extracts from blackberry (Rubus spp. Hull cultivar) by optimizing the processing conditions, and to characterize anthocyanin individuals and determine influences of optimization on enhancement of antioxidant and anti-hyperglycemic activities of anthocyanins as natural supplements. The ethanol concentration of 69.87%, HCl dosage of 0.53%, solid-to-liquid ratio of 1:19.06 at 47.68°C for 17.04 h were optimal to obtain the highest extraction yield of anthocyanins at 0.72 mg/g. By using AB-8 macroporous resins, the anthocyanin concentration of 3.0 mg/mL, ethanol concentration of 90%, and elution rate of 2.0 mL/min were selected to boost the anthocyanin purity up to be 60.11%. Moreover, the purified anthocyanin extracts from blackberry contained nine main pigments which could be divided into three aglycone-based forms, and cyanidin-3-O-glucoside was the most abundant among them. Due to the successive processes of extraction and purification, the blackberry purified anthocyanin extracts (BA-PAE) showed much higher bioactive capacities than the blackberry crude anthocyanin extracts (BA-CAE) and blackberry fruit slurry extracts (BA-FSE), e.g., DPPH and ABTS radical scavenging activities (EC50 = 0.08 and 0.04, 0.32 and 0.24, and 1.31 and 0.41 mg/mL), oxygen radical absorbance capacity (1.60, 0.59, and 0.15 mmol TEAC/g), cytoprotective effects against oxidative stress in PC12 cells (1.69-, 1.58-, and 1.50-fold cell viability compared to oxidative group), α-amylase and α-glucosidase inhibitory activities (IC50 = 0.10 and 0.06, 0.56 and 0.32, and 3.98 and 2.16 mg/mL), and antibacterial activity (93.23, 40.85, and 80.42% reduced biofilm).

BackgroundGastrointestinal bleeding (GIB) is one of the most serious complications of acute myocardial infarction (AMI) and is correlated with poor outcomes.ObjectiveTo evaluate the prevalence, risk factors and in-hospital mortality of GIB in patients with AMI.MethodsThis observational case-control study retrospectively enrolled consecutive patients with AMI from the Department of Cardiovascular Medicine and Cardiovascular Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020. GIB after AMI was identified by International Classification of Diseases (ICD) codes from inpatient medical settings and validated by medical record review. AMI patients without GIB were accordingly classified as the control group. Propensity score matching (PSM) was used to match with the GIB group and the control group. All anonymized clinical data were provided by the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University.ResultsA total of 5,868 AMI patients were enrolled, 0.87% (51/5,868) of whom developed GIB after AMI. On the univariate analysis, history of diabetes, chronic kidney disease, Killip IV, a lower hemoglobin concentration, a higher serum level of creatinine, blood urea nitrogen and D-dimer were closely associated with the risk of GIB (P < 0.05). On the multivariable analysis, a lower hemoglobin concentration (OR: 0.93, 95% CI: 0.89–0.96, P < 0.001) was independently associated with the risk of GIB. Patients with GIB had a much higher in-hospital mortality rate than those without GIB (14.3 vs. 2.1%, P = 0.047). In-hospital mortality among patients with GIB after AMI appeared to be associated with a decreased hemoglobin concentration (OR: 0.93, 95% CI: 0.86–0.99, P = 0.045) and Killip IV (OR: 51.59, 95% CI: 2.65–1,005.30, P = 0.009).ConclusionThe history of diabetes, poor renal function and heart failure were associated with the high risk of GIB in patients experiencing AMI. The in-hospital mortality in patients with AMI complicating GIB was higher than that in patients without GIB and was associated with a decreased hemoglobin concentration and high Killip classification.

Understanding the spatial associations of ecosystem services (ESs) driven by socio-ecological factors is essential for regional ecosystem management and effective resource allocation. Yet previous studies of mechanisms driving ESs have focused mainly on the supply or demand for ESs, rarely consider their threshold effects and supply–demand ratios. Taking the upper reach of Ganjiang watershed (URGW) in southern China as an example, the supply, demand, and supply–demand ratio of ESs (ESDRs) were quantified for grain production (GP), water yield (WY), soil retention (SR), carbon sequestration (CS), and green space recreation (GR). Correlation analysis and random forest models were used to investigate the spatial associations of five ESDRs and the relative importance and marginal effects of 9 socio-ecological factors upon them. At the watershed scale, only SR incurred a supply–demand deficit (ESDR 0). When considered across 188 sub-watersheds, all ESs had different supply–demand deficits. The trade-offs in ESDRs mainly derived from two ESs (GP, SR) and the other three ESs (WY, CS, GR). The supply–demand ratio of SR was mainly determined by topography (i.e., slope gradient), while land use (i.e., proportions of cropland and forest land areas) played a decisive role in the supply–demand ratios of GP and WY. The supply–demand ratios of GR and CS showed similar spatial distribution, driven mainly by the normalized difference vegetation index and human population density. Specific socio-ecological factors (e.g., slope gradient and proportion of forest land area) had significant threshold effects on the ESDRs. Accordingly, research on the mechanisms driving ESs should consider ESs’ supply and demand in tandem, and pay particular attention to the potential threshold effects of socio-ecological factors.

Left atrial appendage (LAA) is believed to be a common site of thrombus formation in patients with atrial fibrillation (AF). However, the commonly-applied stroke risk stratification model (such as. CHA2DS2-VASc score) does not include any structural or hemodynamic features of LAA. Recent studies have suggested that it is important to incorporate LAA geometrical and hemodynamic features to evaluate the risk of thrombus formation in LAA, which may better delineate the AF patients for anticoagulant administration and prevent strokes. This review focuses on the LAA-related factors that may be associated with thrombus formation and cardioembolic events.