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Since determining the weight of pigs during large-scale breeding and production is challenging, using non-contact estimation methods is vital. This study proposed a novel pig weight prediction method based on a modified mask region-convolutional neural network (mask R-CNN). The modified approach used ResNeSt as the backbone feature extraction network to enhance the image feature extraction ability. The feature pyramid network (FPN) was added to the backbone feature extraction network for multi-scale feature fusion. The channel attention mechanism (CAM) and spatial attention mechanism (SAM) were introduced in the region proposal network (RPN) for the adaptive integration of local features and their global dependencies to capture global information, ultimately improving image segmentation accuracy. The modified network obtained a precision rate (P), recall rate (R), and mean average precision (MAP) of 90.33%, 89.85%, and 95.21%, respectively, effectively segmenting the pig regions in the images. Five image features, namely the back area, body length, body width, average depth, and eccentricity, were investigated. The pig depth images were used to build five regression algorithms (ordinary least squares (OLS), AdaBoost, CatBoost, XGBoost, and random forest (RF)) for weight value prediction. AdaBoost achieved the best prediction result with a coefficient of determination (R2) of 0.987, a mean absolute error (MAE) of 2.96 kg, a mean square error (MSE) of 12.87 kg2, and a mean absolute percentage error (MAPE) of 8.45%. The results demonstrated that the machine learning models effectively predicted the weight values of the pigs, providing technical support for intelligent pig farm management.

Abstract The benefits provided by ecological assets play a crucial role in enhancing human well-being. However, there is a scarcity of viable methods for assessing their status. This study is grounded in Land Use and Land Cover Change (LUCC) and integrates both the quantity and quality aspects of these assets. Utilizing the ecological asset index (EQ and EQi), this study conducts a quantitative assessment of the assets in the Shibing karst and the Libo-Huanjiang karst heritage sites, while also qualitatively analyzing their influencing factors. The findings reveal that: (1) In the Shibing heritage site, forest and impervious surface assets exhibited an upward trend, whereas cropland and grassland experienced a decline; meanwhile, shrub and water body assets remained relatively stable. The total area of assets rated as excellent or good increased by 95.371 km2, resulting in an EQ enhancement of 45.427. (2) Likewise, in the Libo-Huanjiang heritage site, forest and impervious surface assets demonstrated an upward trajectory, while shrub assets declined. Cropland, grassland, and water body assets experienced minimal variation. The total area of assets rated as excellent or good expanded by 168.227 km2, resulting in an EQ enhancement of 80.806. (3) The execution of a series of ecological protection projects and management plans for heritage site conservation primarily accounts for the enhancement of regional assets. Notably, ecological resources, socio-economic conditions, human resources, and conservation management policies serve as pivotal drivers influencing the alterations in heritage site assets.

BackgroundAtrial fibrillation (AF) and breast cancer pose significant risks to human health. The reasons behind the concurrent occurrence of AF and breast cancer remain unclear, leading to complex treatment approaches. Mendelian Randomization (MR) analyses aim to offer genetic evidence supporting the causation of AF and breast cancer and to investigate common druggable genes associated with both conditions.MethodsWe used two-samples of MR to sequentially explore the causal relationship between atrial fibrillation and breast cancer, and between atrial fibrillation and breast cancer therapeutic drugs, and verified the stability of the results through colocalization analysis. We utilized the Connectivity map database to infer the direction of drug effects on disease. Finally, we explored druggable genes that play a role in AF and breast cancer and performed a Phenome-wide MR analysis to analyze the potential side effects of drug targets.ResultsWe found 15 breast cancer therapeutic drugs that significantly support a causal association between AF and breast cancer through expression in blood and/or atrial appendage tissue. Among these, activation of ANXA5 by Docetaxel, inhibition of EIF5A by Fulvestrant, and inhibition of GNA12 by Tamoxifen increased the risk of AF, while inhibition of ANXA5 by Gemcitabine and Vinorebine and inhibition of PCGF6 by Paclitaxel reduced the risk of AF. Inhibition of MSH6 and SF3B1 by Cyclophosphamide, as well as inhibition of SMAD4 and PSMD2 and activation of ASAH1 and MLST8 by Doxorubicin can have bidirectional effects on AF occurrence. XBP1 can be used as a common druggable gene for AF and breast cancer, and there are no potential side effects of treatment against this target.ConclusionThis study did not find a direct disease causality between AF and breast cancer but identified 40 target genes for 15 breast cancer therapeutic drugs associated with AF, clarified the direction of action of 8 breast cancer therapeutic drugs on AF, and finally identified one common druggable target for AF and breast cancer.

IntroductionMango is a vital horticultural fruit crop, and breeding is an essential strategy to enhance ongoing sustainability. Knowledge regarding population structure and genetic diversity in mango germplasm is essential for crop improvement.MethodsA set of 284 mango accessions from different regions of the world were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction to generate genomic single-nucleotide polymorphism (SNP).ResultsAfter filtering, raw data containing 539.61 M reads were obtained. A total of 505,300 SLAFs were detected, of which, 205,299 were polymorphic. Finally, 29,136 SNPs were employed to dissect the population structure, genetic relationships, and genetic diversity. The 284 mango accessions were divided into two major groups: one group consisted mainly of mango accessions from Australia, the United States, Cuba, India, Caribbean, Israel, Pakistan, Guinea, Burma, China, and Sri Lanka, which belonged to the Indian type (P1); the other group contained mango accessions from the Philippines, Thailand, Indonesia, Vietnam, Cambodia, Malaysia, and Singapore, which belonged to Southeast Asian type (P2). Genetic diversity, principal component analysis (PCA), and population structure analyses revealed distinct accession clusters. Current results indicated that the proposed hybridization occurred widely between P1 and P2.DiscussionMost of the accessions (80.99%) were of mixed ancestry, perhaps including multiple hybridization events and regional selection, which merits further investigation.

Summary: Bromodomain protein BRD4 binds to acetylated histones to regulate transcription. BRD4 also drives cancer cell proliferation. However, the role of BRD4 in normal cell growth has remained unclear. Here, we investigated this question by using mouse embryonic fibroblasts with conditional Brd4 knockout (KO). We found that Brd4KO cells grow more slowly than wild type cells; they do not complete replication, fail to achieve mitosis, and exhibit extensive DNA damage throughout all cell cycle stages. BRD4 was required for expression of more than 450 cell cycle genes including genes encoding core histones and centromere/kinetochore proteins that are critical for genome replication and chromosomal segregation. Moreover, we show that many genes controlling R-loop formation and DNA damage response (DDR) require BRD4 for expression. Finally, BRD4 constitutively occupied genes controlling R-loop, DDR and cell cycle progression. In summary, BRD4 epigenetically marks above genes and serves as a master regulator of normal cell growth.

Abstract Background Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. Method Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. Result A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794–0.928] P

Abstract Background To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). Methods The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. Results A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (

Abstract Background This study aimed to evaluate the characteristics of mandibular protrusive condylar trajectory in adolescents with skeletal Class II Division 1 malocclusion and the changes of condylar trajectory during mandibular advancement (MA) treatment using clear functional aligners. Methods This prospective study consisted of a cross-sectional study and a longitudinal study. In cross-sectional study, sixty-one adolescents were divided into two groups: Class I (n = 30) and Class II Division 1 (n = 31). The condylar trajectory was measured and compared using the Mann–Whitney U test. The longitudinal study was the MA treatment group using clear functional aligner and consisted of 16 participants from Class II Division 1group. The condylar trajectory was collected at three-time points: pre-treatment (T1), during MA treatment at approximately 3 months (T2, 105.6 days average), and at the end of MA treatment (T3, 237.6 days average). The changes at T1, T2, and T3, as well as the symmetry between the left and right condyles across all groups, were examined using the Wilcoxon paired test. Results A greater increase in the anteroposterior displacement and space displacement during protrusive movements was observed in the Class II Division 1 group compared with that in the Class I group, with a large difference being observed in the left and right condylar movements. The condylar anteroposterior displacement and space displacement decreased significantly at T2 and increased significantly at T3; however, no significant difference was observed between T1 and T3. A significant difference was observed between the condylar movement on the left and right sides at T1; however, no significant difference was observed at T2 and T3. Conclusions Adolescents with Class II Division 1 malocclusion had higher protrusive capacity than those with Class I. Moreover, their left and right condylar motion was more asymmetric. The range of condyle motion decreased first and then increased during MA therapy, and the left and right condyle movement became more symmetrical, which may be the adaptive response of neuromuscular function to the changes in jaw position.

Background & Aims: The nuclear receptor coactivator 5 (NCOA5) is a putative type 2 diabetes susceptibility gene. NCOA5 haploinsufficiency results in the spontaneous development of nonalcoholic fatty liver disease (NAFLD), insulin resistance, and hepatocellular carcinoma (HCC) in male mice; however, the cell-specific effect of NCOA5 haploinsufficiency in various types of cells, including macrophages, on the development of NAFLD and HCC remains unknown. Methods: Control and myeloid-lineage–specific Ncoa5 deletion (Ncoa5ΔM/+) mice fed a normal diet were examined for the development of NAFLD, nonalcoholic steatohepatitis (NASH), and HCC. Altered genes and signaling pathways in the intrahepatic macrophages of Ncoa5ΔM/+ male mice were analyzed and compared with those of obese human individuals. The role of platelet factor 4 (PF4) in macrophages and the underlying mechanism by which PF4 affects NAFLD/NASH were explored in vitro and in vivo. PF4 expression in HCC patient specimens and prognosis was examined. Results: Myeloid-lineage–specific Ncoa5 deletion sufficiently causes spontaneous NASH and HCC development in male mice fed a normal diet. PF4 overexpression in Ncoa5ΔM/+ intrahepatic macrophages is identified as a potent mediator to trigger lipid accumulation in hepatocytes by inducing lipogenesis-promoting gene expression. The transcriptome of intrahepatic macrophages from Ncoa5ΔM/+ male mice resembles that of obese human individuals. High PF4 expression correlated with poor prognosis of HCC patients and increased infiltrations of M2 macrophages, regulatory T cells, and myeloid-derived suppressor cells in HCCs. Conclusions: Our findings reveal a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC.

Abstract Background Our study aimed to use three-dimensional (3D) spatial morphological measurement methods to compare the influence of Twin-Block and clear functional aligners on the temporomandibular joint (TMJ) of adolescent Class II division 1 malocclusion mandibular retraction patients. We also aimed to explore the similarities and differences in the effects on the TMJ upon using Twin-Block and clear functional aligner. Methods Cone-beam computed tomography (CBCT) data of 49 patients with Class II division 1 malocclusion (Twin-Block group: 24; clear functional aligner group: 25) were collected before and after functional orthodontic treatment, and a 3D model of the TMJ was reconstructed using MIMICS 21.0 software. Eighteen measurement parameters, including the anterior, superior, and posterior joint spaces, were measured and compared using the 3D model. Results After the two groups underwent functional appliance treatment, the height, volume, and surface area of the condyle, length of the mandibular ramus and mandibular length increased; The retro-displaced condyle moved to the middle position of the articular fossa, while the rest of the condylar position did not change significantly. Remodeling of the articular fossa after treatment was not evident. The superior joint space of the clear functional aligner group increased, but there was no significant change after Twin-Block appliances treatment. Conclusions Both appliances promote condylar growth and sagittal and vertical development of the mandible in adolescent Class II division 1 malocclusion mandibular retraction patients. The length of the mandibular ramus showed a more significant increase following treatment with the Twin-Block appliances than with clear function aligners.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p

Macrophage pyroptosis plays a significant role in the pathogenesis of various diseases, especially acute lung injury, atherosclerosis, and sepsis. Despite its importance, analysis of the existing literature has been limited. Therefore, we conducted a bibliometric analysis to provide a comprehensive overview of research on macrophage pyroptosis and identify the current research foci and trends in this field. We collected articles related to macrophage pyroptosis published between 2001 and 2022 from the Web of Science Core Collection and PubMed. Citespace, VOSviewer, bibliometrix R package, and Microsoft Excel 2019 were used to analyze co-occurrence relationships and the contribution of countries/regions, institutions, journals, authors, references, and keywords. In total, 1321 papers were included. China and the United States of America published the most articles in this field. TD Kanneganti had the most publications; BT Cookson was the most cited. Although China contributed the most publications, it had a relatively low ratio of multiple-country collaborations (0.132). Among journals, Frontiers in Immunology and Cell Death Disease published the most papers; Nature and the Journal of Immunology were frequently co-cited. Frequently occurring keywords included “inflammation,” “NLRP3 inflammasome,” “apoptosis,” “caspase-1,” and “cell death.” Moreover, with the advancement of gene editing technology and the integration of clinical applications, novel molecules (“caspases,” “GSDMD,” “ASC”), programmed cell death topics (“pyroptosis,” “ferroptosis,” “necrosis”), and clinical applications (“alveolar macrophage,” “atherosclerosis,” “prognosis”) emerged as frontiers. The macrophage pyroptosis field is rapidly evolving and holds promise as a potential target for treating macrophage pyroptosis-related diseases.

Valeriana jatamansi Jones (VJJ), renowned for its extensive history in traditional Chinese medicine and ethnomedicine within China, is prevalently utilized to alleviate ailments such as epigastric distension and pain, gastrointestinal disturbances including food accumulation, diarrhea, and dysentery, as well as insomnia and other diseases. Moreover, the Iridoid-rich fraction derived from Valeriana jatamansi Jones (IRFV) has demonstrated efficacy in facilitating the recuperation of motor functions after spinal cord injury (SCI). This study is aimed to investigate the therapeutic effect of IRFV on SCI and its underlying mechanism. Initially, a rat model of SCI was developed to assess the impact of IRFV on axonal regeneration. Subsequently, employing the PC12 cell model of oxidative damage, the role and mechanism of IRFV in enhancing axonal regeneration were explored using the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway inhibitor LY294002. Ultimately, the same inhibitor was administered to SCI rats to confirm the molecular mechanism through which IRFV promotes axonal regeneration by activating the PI3K/Akt signaling pathway. The results showed that IRFV significantly enhanced motor function recovery, reduced pathological injury, and facilitated axonal regeneration in SCI rats. In vitro experiments revealed that IRFV improved PC12 cell viability, augmented axonal regeneration, and activated the PI3K/Akt signaling pathway. Notably, the inhibition of this pathway negated the therapeutic benefits of IRFV in SCI rats. In conclusion, IRFV promote promotes axonal regeneration and recovery of motor function after SCI through activation of the PI3K/Akt signaling pathway.

Abstract Background Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. Methods Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. Results Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. Conclusions These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX) is a pervasive perfluorinated compound with scant understood toxic effects. Toxicological studies on GenX have been conducted using animal models. To research deeper into the potential toxicity of GenX in humans and animals, we undertook a comprehensive analysis of transcriptome datasets across different species. A rank-in approach was utilized to merge different transcriptome datasets, and machine learning algorithms were employed to identify key genetic mechanisms common among various species and humans. We identified seven genes—TTR, ATP6V1B1, EPHX1, ITIH3, ATXN10, UBXN1, and HPX—as potential variables for classification of GenX-exposed samples, and the seven genes were verified in separate datasets of human, mouse, and rat samples. Bioinformatic analysis of the gene dataset further revealed that mitochondrial function and metabolic processes may be modulated by GenX through these key genes. Our findings provide insights into the underlying genetic mechanisms and toxicological impacts of GenX exposure across different species and offer valuable references for future studies using animal models to examine human exposure to GenX.

BackgroundSalidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques.MethodsRGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software.ResultsIn the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3.ConclusionThis study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.

BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261-12.432; P < 0.001; FDR-corrected P < 0.001) and MI (OR = 2.287; 95% CI 1.218-4.300; P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.

Abstract Purpose Transfusing red blood cells promptly corrects anemia and improves tissue oxygenation in around 40% of patients hospitalized in the intensive care unit (ICU) after major surgical operations. This study’s goal is to investigate how blood transfusions affect the mortality rates of patients after major surgery who are hospitalized in the ICU. Methods Retrospective research was done on recently hospitalized patients who had major procedures in the ICU between October 2020 and February 2022 at the Huanggang Central Hospital of Yangtze University, China. The patients’ prognoses at three months were used to classify them as either survivors or deceased. Patient demographic information, laboratory results, and blood transfusion histories were acquired, and the outcomes of the two groups were compared based on the differences. Univariate and multivariate logistic regression analyses were used to examine the prognosis of surgical disease patients first admitted to the ICU. The receiver operating characteristic (ROC) curve was used to evaluate the predictive power of each risk factor. The relationship between transfusion frequency, transfusion modality, and patient outcome was examined using Spearman’s correlation analysis. Results Data from 384 patients was included in the research; of them, 214 (or 55.7%) died within three months of their first stay in the ICU. The death group had higher scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) than the survival group did (all P = 12 points, SOFA score > = 6, and blood transfusion. When all three indicators were used jointly to predict a patient’s prognosis after major surgery, the accuracy increased to 86.4% (sensitivity) and 100% (specificity). There was a negative correlation between the number of blood transfusions a patient had and their outcome (r = 0.605, P

Abstract Background To compare the severity of radiation-induced lung injury (RILI) after the right lung of SD rats received interstitial brachytherapy and stereotactic radiotherapy (SBRT). Methods RILI rat model was established using interstitial brachytherapy and SBRT methods, respectively. CT scan was performed to analyze the lung volume and the CT value difference between the left and right lungs in rats. Then the lung tissues were analyzed through H&E staining, peripheral blood was extracted to detect the expression levels of serum inflammatory cytokines, pro-fibrotic cytokines, and fibrotic-inhibiting cytokines by ELISA. Results The difference between right and left lung CT values was significantly elevated in the SBRT group when compared with the control group and the interstitial brachytherapy group (P

Abstract Background To investigate changes in the three-dimensional (3D) spatial morphology of the temporomandibular joint (TMJ) and condyle position in adult patients with Class II division 2 malocclusion using a 3D spatial measurement method and to investigate the similarities and differences in the effects of fixed appliance and clear aligner treatments on the TMJ. Methods Cone-beam computed tomography (CBCT) data of 47 adult patients with Class II division 2 malocclusion (25, fixed appliance group; 22, clear aligner group) were collected before and after treatment. Mimics 21.0 was used to reconstruct the TMJ 3D model. Fourteen measurement items, such as the anterior, upper, and posterior joint spaces, were measured directly on the 3D model and compared. Results Post-orthodontic treatment, the shape and position of the condyle changed in adult patients with Class II division 2 malocclusion. Reduction in the anterior joint space and increase in the posterior joint space after orthodontic treatment were significant in both fixed appliance and clear aligner treatments; the condyle moved forward to the center of the fossa. The superior joint space and depth of the glenoid fossa increased after clear aligner treatment, but there was no significant change after fixed appliance treatment. Conclusions The condylar shape and position in patients with Class II division 2 malocclusion changed significantly post-treatment, indicating that the condyle undergoes adaptive reconstruction during orthodontic treatment in these patients. These results provide a reference for diagnosis, design of treatment plan, and monitoring of treatment in orthodontic clinics.

The combustion of diesel fuel in internal combustion engines faces challenges associated with excessive emissions of pollutants. A direct solution to this issue is the incorporation of cleaner energy sources. In this study, a numerical model was constructed to investigate the characteristics of ammonia–diesel dual-fuel application in a medium-speed diesel engine. Effects of ammonia–diesel blending ratios on engine performance and emissions were investigated. The results indicate that for this engine model, the optimal diesel energy ratio is about 22%. When the diesel energy ratio is less than 22%, the engine’s output performance is significantly affected by the diesel energy ratio, while above 22%, the influence of the intake becomes more pronounced. When the diesel energy ratio is below 16%, the cylinder cannot reach combustion conditions. Diesel energy ratios below 22% can cause ammonia leakage. With increasing diesel energy ratio, the final emissions of carbon oxides increase. With a higher diesel energy ratio, NO emissions become lower. When the diesel fuel energy ratio exceeds 22%, the N2O emissions can be almost neglected, while below 22%, with poor combustion conditions inside the cylinder, the N2O emissions will increase.

Understanding soil loss pathways in karst regions is crucial for erosion control. Combining high-density measurements of grid points with runoff plot monitoring, we attempt to use a new indirect method to study the characteristics of soil loss in karst rocky desertification areas of Salaxi Town, Guizhou province. One cycle year monitoring data of 12640 grid points were applied in the soil loss analysis. This study identifies underground leakage as the primary pathway of soil loss, with an mean soil leakage of 21.51 kg in potential areas, accounting for 83.12%, and an average leakage of 22.69 kg in in mild karst rocky desertification areas accounting for 81.48%. Mixed vegetation types (forest, shrub, and grass) were better at preventing surface soil loss but increased underground leakage compared to single vegetation types. The rainy season significantly influences soil erosion, accounting for 67.88% of total loss, with slight variations among different karst rocky desertification grades and vegetation types. Mean underground leakage rates during the rainy and dry seasons are 63.34% and 36.66%, respectively. Although this method still has certain limitations, it plays a positive role in revealing the mechanism of soil erosion processes in karst regions.

Increasingly stringent emission standards have led shippers and port operators to consider alternative energy sources which can reduce emissions while minimizing capital investment. It is essential to understand whether there is a certain economic investment gap for alternative energy. The present work mainly focuses on the simulation study of ships using ammonia and hydrogen fuels arriving at Guangzhou Port to investigate the emission advantages and cost-benefit analysis of ammonia and hydrogen as alternative fuels. By collecting actual data and fuel consumption emissions of ships arriving at Guangzhou Port, the present study calculated the pollutant emissions and cost of ammonia and hydrogen fuels substitution. As expected, it is shown that with the increase of NH3 in fuel, mixed fuels will effectively reduce CO and CO2 emissions. Compared to conventional fuel, the injection of NH3 increases the NOx emission. However, the cost savings of ammonia fuel for CO2, SOx and PM10 reduction are higher than that for NOx. In terms of pollutants, ammonia is less expensive than conventional fuels when applied to the Guangzhou Port. However, the cost of fuel supply is still higher than conventional energy as ammonia has not yet formed a complete fuel supply and storage system for ships. On the other hand, hydrogen is quite expensive to store and transport, resulting in higher overall costs than ammonia and conventional fuels, even if no pollutants are produced. At present, conventional fuels still have advantage in terms of cost. With the promotion of ammonia fuel technology and application, the cost of supply will be reduced. It is predicted that by 2035 ammonia will not only have emission reduction benefits, but also will have a lower overall economic cost than conventional fuels. Hydrogen energy will need longer development and technological breakthroughs due to the limitation of storage conditions.

Summary: Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5+/− mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5+/− male mice but dramatically increases HCC incidence in Ncoa5+/− female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hinders HCC development in female mice. Furthermore, HCN3 amplification and overexpression occur in human HCCs and correlate with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.

We present NICER observations of the accreting X-ray pulsar 1A 0535+262 during its faint state (≲6 × 10 ^36 erg s ^−1 ), observed in several type I and type II outbursts. We discovered a transition of temporal and spectral properties around the luminosity L _t = 3.3 × 10 ^35 erg s ^−1 , below which spectra are relatively soft and the pulse profiles have only a narrow peak. The spectra are harder and a secondary hump gradually appears in the pulse profiles when L ≳ L _t . We discuss possible physical mechanisms for this transition, including different Comptonization seed photons, the disappearance of gas shocks on the neutron star surface, and the combination of plasma and vacuum polarization effects.

We report timing and spectral studies of the high-mass X-ray binary 4U 1700-37 using Insight-HXMT observations carried out in 2020 during its out-of-eclipse state. We found significant variations in flux on a timescale of kilo-seconds, while the hardness (count rate ratio between 10–30 keV and 2–10 keV) remains relatively stable. No evident pulsations were found over a frequency range of 10 ^−3 –2000 Hz. During the spectral analysis, for the first time, we took the configuration of different Insight-HXMT detectors’ orientations into account, which allows us to obtain reliable results even if stable contamination exists in the field of view. We found that the spectrum could be well described by some phenomenological models that are commonly used in accreting pulsars (e.g., a power law with a high energy cutoff) in the energy range of 2–100 keV. We found hints of cyclotron absorption features around ∼16 keV or/and ∼50 keV.

Background The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram’s discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610–0.724]) and 0.697 (95% CIs [0.649–0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

The number of nominations for transboundary world heritage properties has increasingly grown in the context of global integration. At the same time, some scholars who are interested in it have conducted related researches on transboundary properties. However, no comprehensive literature review covering studies on transboundary world heritage properties is available. A systematic literature review based on 79 relevant articles retrieved from Web of Science and China National Knowledge Infrastructure (CNKI) databases was conducted in this paper to increase the richness of transboundary world heritage research. Firstly, quantitative research was conducted, and yearly quantity, theme, content and study area of the published literature were analyzed. Secondly, significant progresses and achievements in the research on transboundary world heritage properties were classified and summarized. Finally, eight critical scientific issues to be solved and the orientation of future research were presented in this study in consideration of the existing research on transboundary world heritage properties.

Conservation of crop wild relatives is critical for plant breeding and food security. The lack of clarity on the genetic factors that lead to endangered status or extinction create difficulties when attempting to develop concrete recommendations for conserving a citrus wild relative: the wild relatives of crops. Here, we evaluate the conservation of wild kumquat (Fortunella hindsii) using genomic, geographical, environmental, and phenotypic data, and forward simulations. Genome resequencing data from 73 accessions from the Fortunella genus were combined to investigate population structure, demography, inbreeding, introgression, and genetic load. Population structure was correlated with reproductive type (i.e., sexual and apomictic) and with a significant differentiation within the sexually reproducing population. The effective population size for one of the sexually reproducing subpopulations has recently declined to ~1,000, resulting in high levels of inbreeding. In particular, we found that 58% of the ecological niche overlapped between wild and cultivated populations and that there was extensive introgression into wild samples from cultivated populations. Interestingly, the introgression pattern and accumulation of genetic load may be influenced by the type of reproduction. In wild apomictic samples, the introgressed regions were primarily heterozygous, and genome-wide deleterious variants were hidden in the heterozygous state. In contrast, wild sexually reproducing samples carried a higher recessive deleterious burden. Furthermore, we also found that sexually reproducing samples were self-incompatible, which prevented the reduction of genetic diversity by selfing. Our population genomic analyses provide specific recommendations for distinct reproductive types and monitoring during conservation. This study highlights the genomic landscape of a wild relative of citrus and provides recommendations for the conservation of crop wild relatives.

BackgroundSecond primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history.MethodsThis cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated.ResultsA total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34–0.37, p

ABSTRACT Mycoplasma genitalium is a prokaryotic microorganism that causes urogenital tract infections. M. genitalium protein of adhesion (MgPa) was essential for M. genitalium attachment and subsequent invasion into host cells. Our prior research confirmed that Cyclophilin A (CypA) was the binding receptor for MgPa and MgPa-CypA interaction can lead to the production of inflammatory cytokines. In this study, we revealed that the recombinant MgPa (rMgPa) could inhibit the CaN-NFAT signaling pathway to reduce the level of IFN-γ, IL-2, CD25, and CD69 in Jurkat cells by binding to the CypA receptor. Moreover, rMgPa inhibited the expressions of IFN-γ, IL-2, CD25, and CD69 in primary mouse T cells. Likewise, the expressions of these T cells activation-related molecules in CypA-siRNA-transfected cells and CypA−/− mouse primary T cell was strengthened by rMgPa. These findings showed that rMgPa suppressed T cell activation by downregulating the CypA-CaN-NFAT pathway, and as a result, acted as an immunosuppressive agent. IMPORTANCE Mycoplasma genitalium is a sexually transmitted bacterium that can co-infect with other infections and causes nongonococcal urethritis in males, cervicitis, pelvic inflammatory disease, premature birth, and ectopic pregnancy in women. The adhesion protein of M. genitalium (MgPa) is the primary virulence factor in the complicated pathogenicity of M. genitalium. This research proved that MgPa could interact with host cell Cyclophilin A (CypA) and prevent T cell activation by inhibiting Calcineurin (CaN) phosphorylation and NFAT nuclear translocation, which clarified the immunosuppression mechanism of M. genitalium to host T cells. Therefore, this study can provide a new idea that CypA can be used for a therapeutic or prophylactic target for M. genitalium infection.

Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3 h, 6 h, and 12 h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.

Sustainable ammonia is one of the leading candidates in the search for alternative clean fuels for marine applications. This paper aims to build a simulation model of a six-cylinder, four-stroke diesel engine to investigate the effects of increasing the ammonia proportion in methanol–ammonia fuel blends on engine performance and emissions. In the present study, the conditions of different speeds and different proportions of ammonia in fuel blends are investigated. The results show that the average effective pressure, brake power, and brake torque increase by about 5% with an increased ammonia substitution ratio. In terms of economic performance, the changes under medium and low speed conditions are not obvious. However, the change in high speed conditions is significant. The brake specific fuel consumption (BSFC) is reduced by 6.6%, and the brake thermal efficiency (BTE) is increased by 4%. It is found that the performance of the engine is best at medium speed. The best performance is achieved with higher efficiency and lower emissions. The present results can provide guidance for the optimization of ammonia–methanol blends and their applications in engines.

Based on consumers' preferences, AI (artificial intelligence) recommendation automatically filters information, which provokes scholars' debate. Supporters believe that by analyzing the consumers' preferences, AI recommendation enables consumers to choose products more quickly and at a lower cost. Critics deem that consumers are more easily trapped in information cocoons because of the use of AI recommendations. This reduces the possibility of consumers contacting a variety of commodities, thus lowering the consumer decision quality. Based on experiments, this paper discusses the moderating role of AI recommendation on the relationship between consumers' preferences and information cocoons. Moreover, it examines the relationship between information cocoons and consumer decision quality. The findings are: AI recommendation strengthens consumers' preferences; consumers' preferences are positively correlated with information cocoons and further lead to the decline of consumers’ decision quality. In the AI era, this paper contributes to revealing the dark sides of AI recommendation and provides empirical evidence for the regulation of AI behaviors.

Abstract Background JAK1 and JAK2 have been implicated in fibrosis and cancer as a fibroblast-related marker; however, their role in liver fibrosis has not been elucidated. Here, we aim to determine the effect and underlying mechanism of JAK1/2 inhibition on liver fibrosis and hepatic stellate cells (HSCs) and further explore the therapeutic efficacy of Ruxolitinib, a JAK1/2 selective inhibitor, on preventing and reversing liver fibrosis in mice. Methods Immunohistochemistry staining of JAK1 and JAK2 were performed on liver tissue in mice with hepatic fibrosis and human liver tissue microarray of liver cirrhosis and liver cancer. LX-2 cells treated with specific siRNA of JAK1 and JAK2 were used to analysis activation, proliferation and migration of HSCs regulated by JAK1/2. The effects of Ruxolitinib (JAK1/2 inhibitor) on liver fibrosis were studied in LX-2 cells and two progressive and reversible fibrosis animal models (carbon tetrachloride (CCl4), Thioacetamide (TAA)). Results We found that JAK1/2 expression was positively correlated with the progression of HCC in humans and the levels of liver fibrosis in mice. Silencing of JAK1/2 down-regulated their downstream signaling and inhibited proliferation, migration, and activation of HSCs in vitro, while Ruxolitinib had similar effects on HSCs. Importantly, Ruxolitinib significantly attenuated fibrosis progression, improved cell damage, and accelerated fibrosis reversal in the liver of mice treated with CCl4 or TAA. Conclusions JAK1/2 regulates the function of HSCs and plays an essential role in liver fibrosis and HCC development. Its inhibitor, Ruxolitinib, may be an effective drug for preventing and treating liver fibrosis.

ABSTRACT Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma and its unique clinicopathological mechanism is unclear. Herein, the expression of endothelin-1 (ET-1) in EBVaGC was lower than of Epstein-Barr virus-negative gastric carcinoma (EBVnGC) and associated with a low frequency of lymph node metastasis of EBVaGC. Functional studies showed that the activation of ET-1/endothelin receptor type A (ETAR) axis could promote cell growth, migration, and antiapoptosis. The expression of the ET-1 gene was unrelated to methylation of its promoter region and miRNAs (-1, -125a, -125b). After being treated with MEK1/2 inhibitor (PD0325901), the inactivation of ERK1/2 pathway resulted in downregulation of ET-1 and forkhead box O1 (FOXO1) expression. Further, FOXO1 knockdown decreased the ET-1 expression. These findings indicated that ET-1 could be involved in development of gastric cancer and EBV could suppress the expression of ET-1 via the regulation of the transcription factor FOXO1 through the MAPK/ERK pathway. IMPORTANCE The relationship between Epstein-Barr virus and gastric cancer has been relatively clear. However, there are still many unresolved mechanisms of the virus in tumorigenesis. In recent years, activation of the endothelin-1 signaling axis has been found to play an important role in tumorigenesis, which is involved in tumor angiogenesis and epithelial-mesenchymal transition. EBV genes. In our study, we found that ET-1 was low-expressed in EBV-positive gastric cancer cells, which was due to the inhibition of ERK signaling by EBNA1 through the repression of FOXO1 expression. The low expression of ET-1 limits the proliferation, migration, and anti-apoptotic ability of tumor cells. These findings contribute to further understanding of the role of EBV in EBV-associated gastric cancer.

Human activities have had a significant impact on ecosystems. Studying landscape patterns and ecosystem services (ES) at the village scale based on land use and land cover (LULC) is essential in addressing current ecosystem issues. Based on GF images, the paper selects village ecosystems of karst desertification control (KDC) as the research object. It uses the landscape pattern index, topographic position index (TPI), and value equivalent method to conduct a spatial and temporal analysis of the ecosystem service value (ESV) of the karst desertification control cycle (2015–2020). The results show that: 1) forest land, orchard land, and construction land increase, and dryland and grassland decrease. The landscape shows an aggregated state, with spreading and connectivity increasing while fragrant diversity is decreasing. 2) The total ecosystem service value increased by CNY 63.45 × 104, with regulating and cultural services on the rise and supply and support services on the decline. 3) With the rise of the TPI, the value of the supply services is inversely U-shaped, while the value of the remaining services increases. This study provides a case study about karst desertification areas for village-scale ecosystem services research.

Abstract Background Previous studies have shown that the N6-methyladenosine (m6A) modification enhances the binding ability of mRNAs/long noncoding RNAs (lncRNAs) to microRNAs (miRNAs), but the impact of this modification on the competitive endogenous RNA (ceRNA) function of circular RNAs (circRNAs) is unclear. Methods We used a human circRNA microarray to detect the expression profiles of circRNAs in 3 pairs of cancer and paracancerous tissues from patients with colorectal cancer (CRC) and 3 pairs of peripheral blood specimens from patients with CRC and healthy individuals. The circRNAs highly expressed in both peripheral blood and tumour tissues of patients with CRC, including circALG1, were screened. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of an expanded sample size was performed to detect the expression level of circALG1 in peripheral blood and tumour tissues of patients with CRC and determine its correlation with clinicopathological features, and circRNA loop-forming validation and stability assays were then conducted. Transwell assays and a nude mouse cancer metastasis model were used to study the function of circALG1 in CRC and the role of altered m6A modification levels on the regulation of circALG1 function. qRT-PCR, western blot (WB), Transwell, RNA-binding protein immunoprecipitation (RIP), RNA antisense purification (RAP), and dual-luciferase reporter gene assays were performed to analyse the ceRNA mechanism of circALG1 and the effect of the m6A modification of circALG1 on the ceRNA function of this circRNA. Results CircALG1 was highly expressed in both the peripheral blood and tumour tissues of patients with CRC and was closely associated with CRC metastasis. CircALG1 overexpression promoted the migration and invasion of CRC cells, and circALG1 silencing and reduction of the circALG1 m6A modification level inhibited CRC cell migration and invasion. In vivo experiments further confirmed the prometastatic role of circALG1 in CRC. Further mechanistic studies showed that circALG1 upregulated the expression of placental growth factor (PGF) by binding to miR-342-5p and that m6A modification enhanced the binding of circALG1 to miR-342-5p and promoted its ceRNA function. Conclusion M6A modification enhances the binding ability of circALG1 to miR-342-5p to promote the ceRNA function of circALG1, and circALG1 could be a potential therapeutic target in and a prognostic marker for CRC.

Abstract Radioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

ABSTRACT Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows an anti-tuberculosis activity but, unlike BDQ, did not prolong QT interval (QT) in animal model studies. This study evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM). Fifty reference strains of different mycobacterial species, and 132 NTM clinical isolates from four commonly isolated NTM species were recruited. The microplate alamarBlue assay was performed to determine the MIC of WX-081 and BDQ. Cytotoxicity assay was performed for both drugs using the THP-1 cells, and the minimum bactericidal concentrations (MBCs) of both drugs against the reference strains of five selected NTM species were also determined. All the tested reference strains had MICs lower than 0.5 μg/mL, with the majority having MICs far below 0.1 μg/mL for WX-081. The epidemiological cut-offs of WX-081 ranged from 0.0156 μg/mL to 0.25 μg/mL against commonly isolated NTM, and this value was comparable with that of BDQ. The MBC/MIC ratios suggest a bacteriostatic activity for both drugs against the five selected NTM species. Cytotoxicity assays indicated that THP-1 cells had nearly 100% viability when exposed to WX-081 for 24 h below 4 μg/mL, 200- to 300-fold the MICs of Mycobacterium intracellulare, Mycobacterium avium, and Mycobacterium kansasii. WX-081 has a strong antimicrobial activity against different NTM species with low cytotoxicity and therefore has the potential to be used for treating NTM infections. IMPORTANCE Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. Over 200 species or subspecies of NTM have been reported, whereas pulmonary diseases in humans are caused mainly by M. avium complex (MAC), M. kansasii, and M. abscessus. Treatment of NTM infection is often challenging as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant-tuberculosis (MDR-TB) may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the antituberculosis efficacy but eliminate the severe side effect of BDQ. This study initially evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM).

In this paper, we study a kind of Stackelberg game where the controlled systems are described by backward stochastic differential delayed equations (BSDDEs). By introducing a new kind of adjoint equation, we establish the sufficient verification theorem for the optimal strategies of the leader and the follower in a general case. Then, we focus on the linear–quadratic (LQ) backward Stackelberg game with delay. The backward Stackelberg equilibrium is presented by the generalized fully coupled anticipated forward–backward stochastic differential delayed Equation (AFBSDDE), which is composed of anticipated stochastic differential equations (ASDEs) and BSDDEs. Moreover, we obtain the unique solvability of the AFBSDDE using the continuation method. As an application of the theoretical results, the pension fund problem with delay effect is considered.

The roles of rainfall with various intensities in hydraulic erosion processes are obviously different. In-depth knowledge about the spatiotemporal variation in extreme rainfall erosivity is critical for soil erosion risk assessment and formulation of response measures. In the period of 1961–2020, more than 390,000 erosive rainfall data from 212 meteorological stations were collected to explore the erosion characteristics of different intensities of rainfall erosivity across southern China. The asymmetric characteristic of extreme rainfall erosion was analyzed and expressed by an asymmetric change index (ACI) defined in this study. Correlation analysis was applied to study the impact of global extreme climate events on the ACI. The results showed that different patterns of precipitation had evident asymmetric characteristics in rainfall erosivity, and fewer high-intensity precipitation events contributed to much higher total rainfall erosivity, particularly for rainstorms (≥100 mm). The ACI of the rainfall erosivity exhibited evident spatial heterogeneity; insignificant increasing trends were found in the ACIs for heavy rainfall, torrential, and rainstorm erosivities over the past 60 years. The change rate of ACI varied greatly on both monthly and interdecadal scales, and the ACI of rainstorms showed the maximum linear increasing trend on the long-time scale. There were significantly high correlations between the ACI and erosive rainfall days and the ACI and erosive rainfall (p < 0.01), and the correlation coefficients were relatively higher from May to October, where the precipitation was concentrated. Additionally, the El Niño-Southern Oscillation and tropical cyclones clearly influenced the spatiotemporal distribution of the ACI and rainfall erosivity but were limited to specific periods and regions. These results could provide a reference for extreme soil erosion event monitoring and control in southern China.

Despite the high demand for STEM (science, technology, engineering, and mathematics) professionals, the STEM talent pipeline continues to leak. A framework of STEM identity could provide insight into why and to what extent individuals engage in STEM-related activities. The present study describes the process of developing and validating an instrument for assessing students’ STEM identity. This instrument was created using the conceptual framework of science identity as its foundation. It aims to conceptualize student STEM identity and extend the STEM identity model. This developmental instrument was examined through expert review, small-scale pilot tests, student interviews, and large-scale field tests. The present study involved 2100 Chinese adolescents from middle and high schools in 10 regions. Factor analysis and Rasch analysis provided evidence of reliability and validity. The final instrument contained four dimensions: recognition, belonging, performance and competence, and interest. Our findings provide multiple sets of evidence for reliability and validity, supporting the appropriate structure of the instrument. It exhibits strong psychometric properties, which can be used to assess sustainability in students’ STEM fields.

ObjectiveTo investigate the association between body mass index (BMI) and overall survival (OS) of patients with stage II/III gastric cancer (GC) after radical gastrectomy, and evaluate the potential influence of perioperative adjuvant chemotherapy (PAC).MethodsMedical records of 2,510 consecutive stage II/III GC patients who underwent curative resection between November 2010 and December 2020 were retrospectively reviewed. The optimal cutoff value of BMI for OS was determined by X-tile. The independent predictive factors for completeness of PAC were identified using univariate and multivariate logistic regression analyses. Cox regression analyses assessed the association among BMI, completeness of PAC, and OS.ResultsOf the 2,510 patients, 813 cases with BMI < 20.3 kg/m2 were classified as belonging in the low BMI group. Further analyses confirmed that low BMI was an independent predictor for incomplete PAC (< 6 cycles, n = 920) and poorer OS (hazard ratio: 1.317, 95% confidence interval: 1.162-1.494, P < 0.001), but neo-adjuvant chemotherapy (NAC) was a protective factor. An additive effect was found in those with both low BMI and incomplete PAC, as they had even worse OS. However, in patients with low BMI, completion of PAC (≥ 6 cycles) significantly improved OS, which became comparable to that in the high BMI group (P = 0.143).ConclusionsLow preoperative BMI independently affects completion of PAC and prognosis of patients with stage II/III GC, but completing PAC can compensate for the adverse influence of low BMI on OS. Thus, strategies designed to ensure the completion of PAC, such as NAC and nutritional support, should be further investigated.

BackgroundThere are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia.PurposeThis study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model.MethodsWe conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria.ResultsSerum RBP4 level had a highly significant association with hyperuricemia (P

Roots of Euphorbia fischeriana and Euphorbia ebracteolata are recorded as the source plant of traditional Chinese medicine “Langdu,” containing active ingredients with anticancer and anti-AIDS activity. However, the two species have specific patterns in the graphic distribution. Compared with E. ehracteolata, E. fischeriana distributes in higher latitude and lower temperature areas and might have experienced cold stress adaptation. To reveal the molecular mechanism of environmental adaptation, RNA-seq was performed toward the roots, stems, and leaves of E. fischeriana and E. ehracteolata. A total of 6,830 pairs of putative orthologs between the two species were identified. Estimations of non-synonymous or synonymous substitution rate ratios for these orthologs indicated that 533 of the pairs may be under positive selection (Ka/Ks > 0.5). Functional enrichment analysis revealed that significant proportions of the orthologs were in the TCA cycle, fructose and mannose metabolism, starch and sucrose metabolism, fatty acid biosynthesis, and terpenoid biosynthesis providing insights into how the two closely related Euphorbia species adapted differentially to extreme environments. Consistent with the transcriptome, a higher content of soluble sugars and proline was obtained in E. fischeriana, reflecting the adaptation of plants to different environments. Additionally, 5 primary or secondary metabolites were screened as the biomarkers to distinguish the two species. Determination of 4 diterpenoids was established and performed, showing jolkinolide B as a representative component in E. fischeriana, whereas ingenol endemic to E. ebracteolate. To better study population genetics, EST-SSR markers were generated and tested in 9 species of Euphorbia. A total of 33 of the 68 pairs were screened out for producing clear fragments in at least four species, which will furthermore facilitate the studies on the genetic improvement and phylogenetics of this rapidly adapting taxon. In this study, transcriptome and metabolome analyses revealed the evolution of genes related to cold stress tolerance, biosynthesis of TCA cycle, soluble sugars, fatty acids, and amino acids, consistent with the molecular strategy that genotypes adapting to environment. The key active ingredients of the two species were quantitatively analyzed to reveal the difference in pharmacodynamic substance basis and molecular mechanism, providing insights into rational crude drug use.

The ever-increasing resolution puts tremendous pressure to the onboard hyperspectral imaging system. Compressed sensing technology is one of the important ways to solve this problem. Distributed compressed sensing was proposed to exploit both intra- and inter-correlation structures of hyperspectral images. However, the implementation method of distributed compressed sampling has not been reported, and the joint sparsity reconstruction algorithm cannot achieve excellent image reconstruction performance. In this paper, a distributed compressed sampling strategy inspired by distributed compressed video sensing and optical implementation model are proposed to collect compressed hyperspectral data. In the image reconstruction process, we discard the direct application of the joint sparsity constraint on the data itself. Instead, we explore the estimation method of abundance and endmember with the help of the existing spectral library. Then, the images are recovered by applying the linear mixing model of hyperspectral. The comparison experiments of various schemes show that the proposed compressed sensing scheme has an obvious advantage in reconstruction performance under the low sampling rate. The proposed compressed sensing scheme has great potential in a high-compression ratio onboard hyperspectral imaging system.

Urban green space is an essential form of infrastructure for cities, providing a significant spatial guarantee for sustainable urban development, an essential ecological, social, and cultural function, and an important symbol of urban modernisation and civilisation. However, with the development of cities, urban problems are becoming more serious, such as the increase in impervious surfaces and urban heat islands and the decrease in urban green space and liveability. Therefore, this study integrates the theories and methods of landscape ecology and spatial syntax with GIS technology to construct a comprehensive model for examining the spatial accessibility of green spaces based on remote images and landscape pattern indices, using Fuzhou City as the study area. The study then incorporates demographic variables to explore the characteristics of an equitable distribution of urban green space at the street scale. The results show that the accessibility of green space in the urban areas of Fuzhou decreases from the centre to the periphery. From north to south, there is a trend of ‘low-high-low’, with the northern region exhibiting the lowest accessibility, followed by the southeastern region, and then the western region. In terms of spatial equity in green space, Fuzhou has a more significant share of surplus green space provision, both in terms of the number of streets and area. This shows that the surplus of green space in Fuzhou is greater than the deficit and that the distribution of space is fair. We hope this study will not only help people gain a deeper understanding of green space but also provide a reference for their rational planning and management, thereby improving the accessibility and equity of urban green space as well as their quality and configuration. We also expect it to provide valuable theoretical and technical support for the planning of ecological functions and sustainable development.

The assessment and prediction of ecological quality can help to quickly and systematically understand the ecological status of World Natural Heritage and assist with developing appropriate strategies to ensure the sustainable and healthy development of that heritage. Using the google earth engine platform, the remote sensing ecological index (RSEI) is rapidly constructed based on principal component analysis to evaluate the spatial and temporal distribution characteristics and the main impact indicators of the ecological environment, and the cellular automata (CA)-Markov model are used to simulate and predict the ecological quality, taking the Libo–Huanjiang karst world natural heritage site as the study area. The results show that: (a) the contribution rate of the four ecological indicators on the first principal component (PC1) are more than 90%. The construction of RSEI based on PC1 are applicable in karst world nature heritage sites and can be used to monitor and evaluate the spatial and temporal variation characteristics of the ecological environment. (b) The mean values of RSEI of the Libo–Huanjiang heritage site during 2000, 2007, 2013 and 2020 were 0.5435, 0.5465, 0.6009 and 0.5101, The overall ecological quality is mainly moderate and good, but in the eastern part of the heritage site the ecological quality is poor. (c) The evolution of the ecological environment quality during 20 years is mainly divided into the development trend of rapidly getting better, slowly getting better, and maintaining stability. (d) In the analysis of the relationship between RSEI and altitude, it is found that the ecological environment quality is mainly inferior, less favorable and moderate in areas with altitudes below 600 m, and there is a positive relationship between ecological quality level and altitude. (e) By analyzing the apparent spatial aggregation between the ecological environment quality, and then simulating the ecological grades in 2027 and 2033 using CA-Markov model, it is predicted that the area of medium and excellent ecological grades will increase in the future, but the ecological environment quality still needs to be improved in the eastern region due to the development of the tourism industry. Overall, the remote sensing ecological index is an effective model for evaluating and monitoring the ecological environment quality of karst heritage sites; the ecological environment quality of the Libo–Huanjiang heritage site is in a steady state of improvement, and the conservation measures of relevant departments are beginning to bear fruit; further coordination between conservation and development is needed to promote the sustainable development of heritage sites and to provide effective solutions for monitoring other karst-like heritage sites.

The evaluation and monitoring of the ecological environment quality of heritage sites can help provide sustainable and healthy development strategies for heritage management organizations. In this study, an ecological evaluation model based on the remote sensing ecological index (RSEI) was used to measure the ecological environment of the Shibing Karst World Heritage Site and its buffer zone and the Moran index and geographic probe model were combined to quantify the ecological environment. The results show that, (1) from 2013 to 2020, the ecological environment quality of the heritage site and buffer zone was moderate to high and the mean RSEI values in the three periods studied were 0.720, 0.723 and 0.742, showing an overall upward and improving trend; (2) ecological environment quality grades of moderate and good accounted for more than 70% of the area, the distribution pattern of ecological environment quality is significantly better at the heritage site than in the buffer zone and the southwest is better than the northeast; (3) the Moran index increased from 0.600 in 2013 to 0.661 in 2020, residing in the first and third quadrants, respectively, with significantly spatial aggregation; and (4) greenness and humidity were shown to play a positive feedback role on the ecological environment quality and the spatial influence ability of humidity and dryness was greater. Overall, the RSEI is an effective method of evaluating and monitoring the ecological environment quality of heritage sites, the ecological environment quality of the Karst heritage site in Shibing is in a steady state of improvement and the relevant departments of heritage conservation need to further coordinate the relationship between conservation and development to promote the sustainable development of the heritage site and provide effective solutions for the monitoring of other Karst World Heritage sites.