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Abstract Background Developing novel germplasm by using wheat wild related species is an effective way to rebuild the wheat resource bank. The Psathyrostachys huashanica Keng (P. huashanica, 2n = 2x = 14, NsNs) is regarded as a superior species to improve wheat breeding because of its multi-resistance, early maturation and numerous tiller traits. Introducing genetic components of P. huashanica into the common wheat background is the most important step in achieving the effective use. Therefore, the cytogenetic characterization and influence of the introgressed P. huashanica large segment chromosomes in the wheat background is necessary to be explored. Results In this study, we characterized a novel derived line, named D88-2a, a progeny of the former characterized wheat-P. huashanica partial amphiploid line H8911 (2n = 7x = 49, AABBDDNs). Cytological identification showed that the chromosomal composition of D88-2a was 2n = 44 = 22II, indicating the addition of exogenous chromosomes. Genomic in situ hybridization demonstrated that the supernumerary chromosomes were a pair of homologues from the P. huashanica and could be stably inherited in the common wheat background. Molecular markers and 15 K SNP array indicated that the additional chromosomes were derived from the sixth homoeologous group (i.e., 6Ns) of P. huashanica. Based on the distribution of the heterozygous single-nucleotide polymorphism sites and fluorescence in situ hybridization karyotype of each chromosome, this pair of additional chromosomes was confirmed as P. huashanica 6Ns large segment chromosomes, which contained the entire short arm and the proximal centromere portion of the long arm. In terms of the agronomic traits, the addition line D88-2a exhibited enhanced stripe rust resistance, improved spike characteristics and increased protein content than its wheat parent line 7182. Conclusions The new wheat germplasm D88-2a is a novel cytogenetically stable wheat-P. huashanica 6Ns large segment addition line, and the introgressed large segment alien chromosome has positive impact on plant spikelet number and stripe rust resistance. Thus, this germplasm can be used for genetic improvement of cultivated wheat and the study of functional alien chromosome segment.

Abstract Large language models (LLMs) are becoming a significant source of content generation in social networks, which is a typical complex adaptive system (CAS). However, due to their hallucinatory nature, LLMs produce false information that can spread through social networks, which will impact the stability of the whole society. The uncertainty of LLMs false information spread within social networks is attributable to the diversity of individual behaviors, intricate interconnectivity, and dynamic network structures. Quantifying the uncertainty of false information spread by LLMs in social networks is beneficial for preemptively devising strategies to defend against threats. To address these challenges, we propose an LLMs hallucination-aware dynamic modeling method via agent-based probability distributions, spread popularity and community affiliation, to quantify the uncertain spreading of LLMs hallucination in social networks. We set up the node attributes and behaviors in the model based on real-world data. For evaluation, we consider the spreaders, informed people, discerning and unwilling non-spreaders as indicators, and quantified the spreading under different LLMs task situations, such as QA, dialogue, and summarization, as well as LLMs versions. Furthermore, we conduct experiments using real-world LLM hallucination data combined with social network features to ensure the validity of the proposed quantifying scheme.

Abstract The color of red-skinned pear (Pyrus spp.) is primarily attributed to accumulation of anthocyanins, which provide nutritional benefits for human health and are closely associated with the commercial value of fruits. Here, we reported the functional characterization of a R2R3-MYB repressor PyMYB107, which forms an ‘activator-repressor’ loop to control anthocyanin accumulation in the red-skinned pear. PyMYB107 overexpression inhibited anthocyanin biosynthesis in both pear calli and fruits, while virus-induced gene silencing of PyMYB107 increased anthocyanin accumulation in pear fruits. Furthermore, ectopic expression of PyMYB107 decreased anthocyanin accumulation in tomato, strawberry and tobacco. PyMYB107 can competitively bind to PybHLH3 with PyMYB10/MYB114, thereby suppressing the transcriptional activation of key anthocyanin biosynthesis genes, PyANS and PyUFGT. Site-directed mutagenesis showed that mutations within the R3 domain and EAR motif of PyMYB107 eliminated its repressive activity. Additionally, PyMYB107 exhibited a comparable expression pattern to PyMYB10/MYB114 and was transcriptionally activated by them. Our finding advanced comprehension of the repression mechanism underlying anthocyanin accumulation, providing valuable molecular insights into improving quality of pear fruits.

China is a country in the world with the serious environmental pollution of coal mine “three wastes” (solid, liquid, gas). A lot of in-depth research and practice has been carried out on the utilization and treatment of “three wastes”. However, there are still many problems such as imperfect standards and norms, small scale of treatment and unsound technology. In order to solve the problem of synergistic development of low-cost geological storage of large-scale “three wastes” and ecological environment in China’s coal mines, on the basis of the definition of geological storage in other countries, the connotation of geological storage in China has been expanded. The progress and current status of research on the geological storage of “three wastes” are analyzed. Literature and patents related to the geological storage of “three wastes” at home and abroad are reviewed. The problems faced by China in carrying out the geological storage of “three wastes” and the suggestions for further development are put forward. It is pointed out that the main problem faced by the geological storage of “three wastes” in China is the inadequacy of the standards and regulations in the field of environment, especially the extensive lack of standards for the deep-well injection of waste liquids. The systematic research has shown that the research institutions in China are paying increasing attention to research in the field of the geological storage of the “three wastes”, and that the results of the research account for a high percentage of research in the world. China’s coal mine “three wastes” geological storage and ecological environment synergistic development awareness and system is being formed. However, there is insufficient support for research on the large-scale geological storage of “three wastes”, the cyclic system of geological storage of “three wastes” in the whole cycle of coal mining, and the synergistic relationship between CO2 capture, utilization and storage (CCUS) technology and the ecological environment. This seriously restricts the large-scale implementation and application of the concepts, technologies and projects of geological storage. China should expeditiously strengthen the scientific and technological research and development of coal mine “three wastes” geological storage technology and ecological environment synergistic development. Through the establishment of improved standards and norms, increased technological research and development, and strengthened environmental supervision and other measures, the green and sustainable development in China’s coal mines is promoted, helping the China’s “dual-carbon” goal to be realized.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

With the rapid progress of information technology and life sciences, artificial intelligence (AI) technology has substantially changed the way in many areas of biomaterials and biomedicine, including biomaterials and formulation design, drug development, preclinical study, clinical diagnosis and treatment, as well as health management. This perspective outlines the key issues of AI in the fields of biomaterials and biomedicine applications, and analyzes some opportunities and challenges of AI in the biomedical and clinical development. The gap between experts from multiple disciplines and fields needs to be narrowed, and common participation should be applied to open the next frontier of integrated AI-biomedicine.

Abstract Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

Abstract Gastrointestinal stromal tumors (GISTs) predominantly develop in the stomach. While nomogram offer tremendous therapeutic promise, there is yet no ideal nomogram comparison customized specifically for handling categorical data and model selection related gastric GISTs. (1) We selected 5463 patients with gastric GISTs from the SEER Research Plus database spanning from 2000 to 2020; (2) We proposed an advanced missing data imputation algorithm specifically designed for categorical variables; (3) We constructed five Cox nomogram models, each employing distinct methods for the selection and modeling of categorical variables, including Cox (Two-Stage), Lasso-Cox, Ridge-Cox, Elastic Net-Cox, and Cox With Lasso; (4) We conducted a comprehensive comparison of both overall survival (OS) and cancer-specific survival (CSS) tasks at six different time points; (5) To ensure robustness, we performed 50 randomized splits for each task, maintaining a 7:3 ratio between the training and test cohorts with no discernible statistical differences. Among the five models, the Cox (Two-Stage) nomogram contains the fewest features. Notably, at Near-term, Mid-term, and Long-term intervals, the Cox (Two-Stage) model attains the highest Area Under the Curve (AUC), top-1 ratio, and top-3 ratio in both OS and CSS tasks. For the prediction of survival in patients with gastric GISTs, the Cox (Two-Stage) nomogram stands as a simple, stable, and accurate predictive model with substantial promise for clinical application. To enhance the clinical utility and accessibility of our findings, we have deployed the nomogram model online, allowing healthcare professionals and researchers worldwide to access and utilize this predictive tool.

Abstract Purpose Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study. Methods Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates. Results Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029–1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy. Conclusions This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Abstract Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (T c) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a T c value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high T c and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-T c ferroelectrics with various physical properties.

An innovative metallic buffer consisting of series-connected hat-shaped entangled wire mesh damper (EWMD) and parallel springs are proposed in this work to enhance the reliability of engineering equipment. The impact response and the energy dissipation mechanism of hat-shaped EWMD under different quasi-static compression deformations (2–7 mm) and impact heights (100–200 mm) are investigated using experimental and numerical methods. The results demonstrate distinct stages in the quasi-static mechanical characteristics of hat-shaped EWMD, including stiffness softening, negative stiffness, and stiffness hardening. The loss factor gradually increases with increasing compression deformation before entering the stiffness hardening stage. Under impact loads, the hat-shaped EWMD exhibits optimal impact energy absorption when it enters the negative stiffness stage (150 mm), resulting in the best impact isolation effect of metallic buffer. However, the impact energy absorption significantly decreases when hat-shaped EWMD enters the stiffness hardening stage. Interestingly, quasi-static compression analysis after experiencing different impact loads reveals the disappearance of the negative stiffness phenomenon. Moreover, with increasing impact loads, the stiffness hardening point progressively shifts to an earlier stage.

Abstract Background The application of radiomics in thoracic lymph node metastasis (LNM) of lung adenocarcinoma is increasing, but diagnostic performance of radiomics from primary tumor to predict LNM has not been systematically reviewed. Therefore, this study sought to provide a general overview regarding the methodological quality and diagnostic performance of using radiomic approaches to predict the likelihood of LNM in lung adenocarcinoma. Methods Studies were gathered from literature databases such as PubMed, Embase, the Web of Science Core Collection, and the Cochrane library. The Radiomic Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were both used to assess the quality of each study. The pooled sensitivity, specificity, and area under the curve (AUC) of the best radiomics models in the training and validation cohorts were calculated. Subgroup and meta-regression analyses were also conducted. Results Seventeen studies with 159 to 1202 patients each were enrolled between the years of 2018 to 2022, of which ten studies had sufficient data for the quantitative evaluation. The percentage of RQS was between 11.1% and 44.4% and most of the studies were considered to have a low risk of bias and few applicability concerns in QUADAS-2. Pyradiomics and logistic regression analysis were the most commonly used software and methods for radiomics feature extraction and selection, respectively. In addition, the best prediction models in seventeen studies were mainly based on radiomics features combined with non-radiomics features (semantic features and/or clinical features). The pooled sensitivity, specificity, and AUC of the training cohorts were 0.84 (95% confidence interval (CI) [0.73–0.91]), 0.88 (95% CI [0.81–0.93]), and 0.93(95% CI [0.90–0.95]), respectively. For the validation cohorts, the pooled sensitivity, specificity, and AUC were 0.89 (95% CI [0.82–0.94]), 0.86 (95% CI [0.74–0.93]) and 0.94 (95% CI [0.91–0.96]), respectively. Conclusions Radiomic features based on the primary tumor have the potential to predict preoperative LNM of lung adenocarcinoma. However, radiomics workflow needs to be standardized to better promote the applicability of radiomics. Trial registration CRD42022375712.

Abstract Background Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. Methods A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. Results Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized β [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. Conclusions Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.

Abstract Pigeon pea (Cajanus cajan L.) is one of the most important legume crops grown in subtropical and tropical regions with high nutritional quality. However, the consumption of pigeon pea is very limited worldwide owing to its high level of anti‐nutrients, hard texture, and unpleasant characteristic taste. The present review summarized the nutritional profile and health benefit of pigeon pea with special attention to its bioactive phytochemicals (e.g., cajanin, cajanol, and cajaninstilbene acid). Furthermore, some aspects that can help promote the application of pigeon pea in foods were highlighted from the perspectives of physical (i.e., thermal, extrusion, and ultrasound‐assisted), chemical (i.e., chemical modification and enzymatic hydrolysis), and biological treatment (i.e., sprouting and fermentation). The primary impact of physical methods was confined to the mitigation of anti‐nutrients. Chemical approaches were less explored and mainly targeted on the modification of starch and protein in pigeon pea. In contrast, the biological methods were found to decrease the level of anti‐nutritional factors, increase the production of bioactive phytochemicals, and improve the sensory properties of pigeon pea. Therefore, biological methods, especially sprouting techniques, are considered to be more promising.

Abstract Background Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. Materials and methods The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and β-glycerophosphate (β-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. Results In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/β-GP-induced VSMCs. In HG/β-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/β-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. Conclusion EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.

Abstract Background Sesterterpenoids are rare species among the terpenoids family. Ophiobolins are sesterterpenes with a 5-8-5 tricyclic skeleton. The oxidized ophiobolins exhibit significant cytotoxic activity and potential medicinal value. There is an urgent need for large amounts of ophiobolins supplication for drug development. The synthetic biology approach has been successfully employed in lots of terpene compound production and inspired us to develop a cell factory for ophiobolin biosynthesis. Results We developed a systematic metabolic engineering strategy to construct an ophiobolin biosynthesis chassis based on Saccharomyces cerevisiae. The whole-cell biotransformation methods were further combined with metabolic engineering to enhance the expression of key ophiobolin biosynthetic genes and improve the supply of precursors and cofactors. A high yield of 5.1 g/L of ophiobolin F was reached using ethanol and fatty acids as substrates. To accumulate oxidized ophiobolins, we optimized the sources and expression conditions for P450-CPR and alleviated the toxicity of bioactive compounds to cells through PDR engineering. We unexpectedly obtained a novel ophiobolin intermediate with potent cytotoxicity, 5-hydroxy-21-formyl-ophiobolin F, and the known bioactive compound ophiobolin U. Finally, we achieved the ophiobolin U titer of 128.9 mg/L. Conclusions We established efficient cell factories based on S. cerevisiae, enabling de novo biosynthesis of the ophiobolin skeleton ophiobolin F and oxidized ophiobolins derivatives. This work has filled the gap in the heterologous biosynthesis of sesterterpenoids in S. cerevisiae and provided valuable solutions for new drug development based on sesterterpenoids.

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

In this Correspondence, B. Minassian and colleagues report that GHF201, an autophagy activator shown to diminish abnormal glycogen aggregates in a mouse model of Adult Polyglucosan Body Disease, fails to reduce such accumulations in a mouse model of Lafora disease.

Abstract Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical. Graphic Abstract

Abstract Background DNA methylation is an essential epigenetic modification. However, its contribution to trait changes and diversity in the domestication of perennial fruit trees remains unknown. Results Here, we investigate the variation in DNA methylation during pear domestication and improvement using whole-genome bisulfite sequencing in 41 pear accessions. Contrary to the significant decrease during rice domestication, we detect a global increase in DNA methylation during pear domestication and improvement. We find this specific increase in pear is significantly correlated with the downregulation of Demeter-like1 (DML1, encoding DNA demethylase) due to human selection. We identify a total of 5591 differentially methylated regions (DMRs). Methylation in the CG and CHG contexts undergoes co-evolution during pear domestication and improvement. DMRs have higher genetic diversity than selection sweep regions, especially in the introns. Approximately 97% of DMRs are not associated with any SNPs, and these DMRs are associated with starch and sucrose metabolism and phenylpropanoid biosynthesis. We also perform correlation analysis between DNA methylation and gene expression. We find genes close to the hypermethylated DMRs that are significantly associated with fruit ripening. We further verify the function of a hyper-DMR-associated gene, CAMTA2, and demonstrate that overexpression of CAMTA2 in tomato and pear callus inhibits fruit ripening. Conclusions Our study describes a specific pattern of DNA methylation in the domestication and improvement of a perennial pear tree and suggests that increased DNA methylation plays an essential role in the early ripening of pear fruits.

A reliable geological model plays a fundamental role in the efficiency and safety of mountain tunnel construction. However, regional models based on limited survey data represent macroscopic geological environments but not detailed internal geological characteristics, especially at tunnel portals with complex geological conditions. This paper presents a comprehensive methodological framework for refined modeling of the tunnel surrounding rock and subsequent mechanics analysis, with a particular focus on natural space distortion of hard-soft rock interfaces at tunnel portals. The progressive prediction of geological structures is developed considering multi-source data derived from the tunnel survey and excavation stages. To improve the accuracy of the models, a novel modeling method is proposed to integrate multi-source and multi-scale data based on data extraction and potential field interpolation. Finally, a regional-scale model and an engineering-scale model are built, providing a clear insight into geological phenomena and supporting numerical calculation. In addition, the proposed framework is applied to a case study, the Long-tou mountain tunnel project in Guangzhou, China, where the dominant rock type is granite. The results show that the data integration and modeling methods effectively improve model structure refinement. The improved model's calculation deviation is reduced by about 10% to 20% in the mechanical analysis. This study contributes to revealing the complex geological environment with singular interfaces and promoting the safety and performance of mountain tunneling.

[Objective] In order to thoroughly implement the national strategy of building China with a strong transportation network and the low-carbon assembly and construction concepts such as standardization, intelligence and refinement, and to address the problems of insufficient construction accuracy, outdated construction equipment, lack of maintenance methods, and poor overall life cycle systematicity caused by the current cast-in-place ballast, which is presently the main track structure in urban rail transit, it is necessary to make research on high-precision prefabricated track technology for urban rail transit. [Method] In terms of the prefabricated tracks, theoretical research and scheme design, effect experiments and verification, and online monitoring of track conditions are carried out in accordance with the overall research and development technology route of "standardized design, factory production, mechanized construction, high-precision control, and full life management", and based on the Phase II and Phase III construction projects of Shanghai Metro. The application effect of the high-precision prefabricated track is briefly introduced. [Result & Conclusion] The key technologies of prefabricated track in urban rail transit, including high-precision prefabrication and assembly technology, energy saving construction facility technology, green construction technology and intelligent monitoring technology are developed, significantly improving the quality of rail construction, rail operation and maintenance. The application of high precision prefabricated track technology improves the construction precision of track structure effectively, improves the indicators like excellent geometry, stability and smoothness of the track structure significantly. Series of trackless construction equipment saves a lot of manpower, material resources and time cost during construction. The application of track condition online monitoring system and management platform reduces the workload of manual inspection by 30%~40%, increases the maintenance efficiency by 20%~30% and the disease detection rate by 30%~40%, reducing the environmental impact of urban rail transit train operation.

Abstract Cuproptosis and disulfidptosis, recently discovered mechanisms of cell death, have demonstrated that differential expression of key genes and long non-coding RNAs (lncRNAs) profoundly influences tumor development and affects their drug sensitivity. Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, presently lacks research utilizing cuproptosis and disulfidptosis-related lncRNAs (CDRLRs) as prognostic markers. In this study, we analyzed RNA-seq data, clinical information, and mutation data from The Cancer Genome Atlas (TCGA) on ccRCC and cross-referenced it with known cuproptosis and disulfidptosis-related genes (CDRGs). Using the LASSO machine learning algorithm, we identified four CDRLRs—ACVR2B-AS1, AC095055.1, AL161782.1, and MANEA-DT—that are strongly associated with prognosis and used them to construct a prognostic risk model. To verify the model's reliability and validate these four CDRLRs as significant prognostic factors, we performed dataset grouping validation, followed by RT-qPCR and external database validation for differential expression and prognosis of CDRLRs in ccRCC. Gene function and pathway analysis were conducted using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) for high- and low-risk groups. Additionally, we have analyzed the tumor mutation burden (TMB) and the immune microenvironment (TME), employing the oncoPredict and Immunophenoscore (IPS) algorithms to assess the sensitivity of diverse risk categories to targeted therapeutics and immunosuppressants. Our predominant objective is to refine prognostic predictions for patients with ccRCC and inform treatment decisions by conducting an exhaustive study on cuproptosis and disulfidptosis.

Abstract Aiming at oil extraction from a tight reservoir, the Jilin oil field was selected as the research object of this study. Based on the molecular structures of conventional long-chain alkyl anionic surfactants, a new temperature-resistant anionic/nonionic surfactant (C8P10E5C) was prepared by introducing polyoxyethylene and polyoxypropylene units into double-chain alcohols. The resulting structures were characterized by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (1H-NMR), and electrospray ionization mass spectrometry (ESI–MS). Then, based on surface tension, interfacial tension, adsorption resistance, wettability, and emulsification performance tests, the performance of C8P10E5C was evaluated. The FT-IR, ESI–MS, and NMR spectra confirmed that C8P10E5C was successfully prepared. The critical micelle concentration (CMC) of C8P10E5C in water was 2.9510 × 10−4 mol/L (the corresponding mass concentration is 0.26%), and the surface tension of the aqueous C8P10E5C solution at this concentration was 30.5728 mN/m. At 0.3% concentration, the contact angle of the C8P10E5C solution was 31.4°, which is 60.75% lower than the initial contact angle. Under high-temperature conditions, C8P10E5C can still reduce the oil–water interfacial tension to 10−2 mN/m, exhibiting good temperature resistance. At 110 °C, upon adsorption to oil sand, the C8P10E5C solution could reduce the oil–water interfacial tension to 0.0276 mN/m, and the interfacial tension can still reach the order of 10−2 mN/m, indicating that C8P10E5C has strong anti-adsorption capability. Additionally, it has good emulsifying performance; upon forming an emulsion with crude oil, the highest drainage rate was only 50%. The forced imbibition oil recovery of C8P10E5C is 65.8%, which is 38.54, 24.22, and 27.25% higher than those of sodium dodecyl benzene sulfonate, alkyl polyoxyethylene ether carboxylate, and alkyl ether carboxylate, respectively.

Genomic selection (GS) has the potential to improve selection efficiency and shorten the breeding cycle in fruit tree breeding. In this study, we evaluated the effect of prediction methods, marker density and the training population (TP) size on pear GS for improving its performance and reducing cost. We evaluated GS under two scenarios: (1) five-fold cross-validation in an interspecific pear family; (2) independent validation. Based on the cross-validation scheme, the prediction accuracy (PA) of eight fruit traits varied between 0.33 (fruit core vertical diameter) and 0.65 (stone cell content). Except for single fruit weight, a slightly better prediction accuracy (PA) was observed for the five parametrical methods compared with the two non-parametrical methods. In our TP of 310 individuals, 2 000 single nucleotide polymorphism (SNP) markers were sufficient to make reasonably accurate predictions. PAs for different traits increased by 18.21%–46.98% when the TP size increased from 50 to 100, but the increment was smaller (−4.13%–33.91%) when the TP size increased from 200 to 250. For independent validation, the PAs ranged from 0.11 to 0.45 using rrBLUP method. In summary, our results showed that the TP size and SNP numbers had a greater impact on the PA than prediction methods. Furthermore, relatedness among the training and validation sets, and the complexity of traits should be considered when designing a TP to predict the test panel.

During the course of ionospheric heating experiments, researchers at the European Incoherent Scatter Scientific Association (EISCAT) observed an apparent electron density enhancement. The enhancement extended over a wide range of altitudes, above the reflection altitude of the high-frequency pump wave. However, whether this enhancement actually corresponds to a true enhancement in electron density remains an open question. When the dispersion relation of ion acoustic waves is followed, the frequency ratio of the enhanced ion line to the background ion line suggests that the profile of the effective ion mass may have remained unchanged. Furthermore, the solar radio flux and ion drift velocity indicate no significant changes in the ion species and their densities. In conclusion, the electron density enhancement observed at EISCAT should not, in fact, be considered a true enhancement.

Carbon dots (CDs) are carbon-based zero-dimensional nanomaterials with characteristic sizes of less than 10 ​nm. Recently, bioactive CDs have made remarkable achievements in wound healing, bone and cartilage repair, neural regeneration, and myocardium regeneration owing to their unique physicochemical properties and excellent biocompatibility, which have significantly promoted the advancement of tissue engineering. Herein, we summarize the applications of bioactive CDs in tissue engineering. First, we briefly introduce the characteristics and synthesis methods of bioactive CDs. Subsequently, we review the applications of bioactive CDs in wound healing, bone and cartilage tissue engineering, neural tissue engineering, and cardiac tissue engineering in detail. Finally, we discuss the challenges and prospects of bioactive CDs in tissue engineering.

The purpose of this paper was to investigate the influence of the magnetisation frequency (40, 80, 120, 160, 200 times) and current velocity (0.84, 1.35, 1.72 m/s) on the surface tension and contact angle of deionised water (DW) to prepare magnetised water (MW). The deionised water (DW) was treated by a self-made permanent magnet magnetiser (B=0.55 T) to prepare the MW. Then, the influence of the MW on the compressive strength and the microstructure of the mortar was investigated. The results showed that when the magnetisation frequency was 80 times and the current velocity was 1.72 m/s, the surface tension and contact angle of the MW decreased by 13.16% and 5.35%, respectively. Moreover, the magnetisation mechanism of MW could be explained by the hydrogen bond breaking in the water molecules caused by the Lorentz force. Besides, compared with the DW mortar, the 28-day compressive strength of the MW mortar increased by 6.63% due to its denser microstructure because more hydrated calcium silicate (C-S-H) and portlandite with smaller crystal sizes were generated.

Aiming at the problem that coal seam development disturbs the stability of oil and gas trap layer and oil and gas shaft in the coordinated exploitation of coal and oil and gas, two-dimensional simulation test was used to carry out the research on the response law of coal and oil and gas mining strata. The mining process of “oil and gas first, then coal” was adopted to obtain the stress evolution, fracture deformation characteristics of coal and oil and gas overlaying strata and the deformation and failure law of oil and gas shaft. The results show that: if the intensity of oil and gas extraction to the completion of recovery, the overall structure of the model does not appear obvious disturbance, only the local inter-layer rock stress concentration phenomenon, and the coal seam mining at this time will cause a certain disturbance to the oil and gas layer at 200 m below. In the early stage of mining, the stress above the oil and gas layer recovery boundary keeps rising; there is a phenomenon of stress transfer in the coal seam floor, no obvious stress change in the roof of the coal seam. The initial disturbance range is 100 m, and the secondary disturbance range is 75 m. When the full mining stage is entered, the stress concentration above the oil and gas recovery boundary shifts horizontally to the right side, and the coal seam floor experiences the process of stress concentration-pressure relief successively. The interlayer strata structure tends to be stable, and the strata migration degree gradually shifts to the strata near the top of the coal seam. It shows that coal seam mining has a great influence on the stability of the whole strata in the process of coordinated exploitation of superposed resources, so we should pay more attention to the influence of coal seam mining on coordinated exploitation of coal and oil and gas. The main failure mode of the inner shaft in overlying rock is shear deformation failure, while the lower shaft at the center of the working face is tension-shear deformation failure. Attention should be paid to the shaft protection at the center of the working face.

Abstract Objective Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. Methods This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. Results We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. Conclusion We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.

Abstract The power of three-dimensional printing in designing personalized scaffolds with precise dimensions and properties is well-known. However, minimally invasive implantation of complex scaffolds is still challenging. Here, we develop amphiphilic dynamic thermoset polyurethanes catering for multi-material four-dimensional printing to fabricate supportive scaffolds with body temperature-triggered shape memory and water-triggered programmable deformation. Shape memory effect enables the two-dimensional printed pattern to be fixed into temporary one-dimensional shape, facilitating transcatheter delivery. Upon implantation, the body temperature triggers shape recovery of the one-dimensional shape to its original two-dimensional pattern. After swelling, the hydrated pattern undergoes programmable morphing into the desired three-dimensional structure because of swelling mismatch. The structure exhibits unusual soft-to-stiff transition due to the water-driven microphase separation formed between hydrophilic and hydrophobic chain segments. The integration of shape memory, programmable deformability, and swelling-stiffening properties makes the developed dynamic thermoset polyurethanes promising supportive void-filling scaffold materials for minimally invasive implantation.

This study used ultrasound-enzyme-assisted deep eutectic solvents to establish a green and highly efficient total flavonoids extraction process from mulberry leaves. On the basis of the results of single-factor experiments, the extraction amount of total flavonoids was used as the response value, and the Box-Behnken response surface method was used to optimize, and the antioxidative ability of total flavonoids from mulberry leaves on DPPH radicals and ABTS+ radicals was studied. The results showed that when the choline chloride/fructose/alcohol molar ratio was 1:1:3, water content 30%, liquid-solid ratio 40 mL/g, ultrasonic power 360 W, ultrasonic temperature 40 ℃, ultrasonic time 40 min, dosage of enzyme 4%, the extraction amount of total flavonoids from mulberry leaves reached 46.58 mg/g. When the mass concentration of total flavonoids from mulberry leaves was 0.08 mg/mL, the scavenging rate of DPPH radicals was 98.36%. And when the mass concentration of total flavonoids from mulberry leaves was 0.2 mg/mL, the scavenging rate of ABTS+ radicals was 72.12%. Therefore, the ultrasonic-enzyme-assisted deep eutectic solvents method was green and simple to operate, and could effectively improve the extraction yield of total flavonoids from mulberry leaves. This method provided a scientific basis for the development and utilization of mulberry leaf resources.

Our understanding of the DNA damage responses of human cells to radiation has increased remarkably over the recent years although some notable signaling events remain to be discovered. Here we provide a brief account of the key molecular events of the responses to reflect the current understanding of the key underlying mechanisms involved.

In this study, a new lunar regolith simulant, named ''GCD-1'', was formulated by combining various minerals, such as anorthite, albite, pyroxene, ilmenite, slag, and fly ash. Through X-ray fluorescence spectroscopy (XRF) and X-ray diffraction (XRD) analysis, it was verified that the main mineral composition of GCD-1 was basically the same as that of the lunar soil at the Apollo 14 landing site, in which the deviation in the main compound (i.e., SiO2 and Al2O3) was within 0.5%. Furthermore, GCD-1 based geopolymer was prepared by the one-part method, which was a mixture of solid GCD-1 precursor, solid sodium silicate (SS) activator, and water. The average daytime temperature at the lunar equator, which was calculated to be 60°C, was set as the curing temperature for the GCD-1 based geopolymer. The strength development of the GCD-1 based geopolymer was then characterized by unconfined compressive strength (UCS) for 3, 7, and 12 curing days to consider the effectiveness of the factors (solid SS to lunar regolith simulant [S/L] and water to binder ratio [W/B]). The micro-analysis tests including scanning electron microscope-energy dispersive spectrometer (SEM-EDS), mercury intrusion porosimetry (MIP), and brunner-emmet-teller (BET), were further conducted to investigate the microstructural development of the GCD-1 based geopolymer. Results showed that the increase of the W/B ratio in the GCD-1 based geopolymer tended to increase the total porosity of the sample, thereby inducing a lower UCS. At the same time, for a fixed W/B ratio, the higher S/L ratio had a certain inhibition effect on the hydration reaction, which caused the reduction in the UCS of the sample. The highest UCS of the GCD-1 based geopolymer reaching 30.54 MPa, was achieved under the simulated lunar equatorial daytime temperature for 12 days with W/B and S/L ratios set at 0.25 and 0.18, respectively. Microstructure and mineralogy analyses indicated that the hydrated sodium aluminosilicate (N-A-S-H) gels contributed to reducing the sample's porosity, thereby enhancing the UCS. The relationship between the UCS and total porosity of GCD-1 based geopolymer was then derived. The results of the current study are crucial for lunar base construction with in-situ resources.

Developing efficient materials for capturing and storing CO2 is crucial in addressing the environmental crisis caused by excessive CO2 emissions. This paper presents the synthesis of amino-modified mesoporous carbon materials with high specific surface areas and efficient adsorption capabilities. The materials were synthesized using resol as the carbon source, F127 as the soft template agent, dicyandiamide as the amino-modified material, and a mixture of ethanol and water as the solvent. The structure and morphology of the amino-modified mesoporous carbon materials were characterized using N2 adsorption/desorption, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). The CO2 adsorption performance and mechanism of the materials were also investigated. The potential application of amino-modified mesoporous carbon materials in carbon capture technology, specifically in shield tunnels, was discussed. The results showed that the amino-modified mesoporous carbon materials exhibited a large surface area (656 m2/g), a highly ordered mesoscopic structure (P6mm space group), and high nitrogen content, which resulted in excellent CO2 adsorption capability. At 25 ℃, it demonstrated a CO2 adsorption capacity of 2.85 mmol/g, indicating both high adsorption capacity and rapid adsorption rate. Additionally, the material exhibited good selectivity for CO2. Moreover, it is estimated that every 5 g of synthesized amino-modified mesoporous carbon material can adsorb 0.627 g of CO2. The implementation of amino-modified mesoporous carbon materials on the inner surface of all tunnel segments in Beiheng Passageway in Shanghai, China could significantly enhance the daily capacity for CO2 adsorption, reaching an impressive 181,830 kg. This study incorporates CO2 capture and storage materials into tunnel engineering, paving a way towards decarbonizing underground space.

The dynamic properties of concrete structures after being exposed to high temperatures play a crucial role in post-disaster repair and accident prevention measures. This study examined three different mixture ratios of Steel Fiber Reinforced Concrete (SFRC) with matrix strength of C60 and steel fiber contents of 0%, 1%, and 2%. A Split Hopkinson Pressure Bar (SHPB) with a diameter of 75 mm, along with a heating furnace, was employed to comprehensively investigate the dynamic compression behavior of materials. The specimens were exposed to temperatures ranging from 200 °C to 600 °C. In addition to evaluating the extent of mechanical degradation in SFRC after cooling, auxiliary impact experiments were also carried out at ambient temperature. The experimental data revealed that the dynamic peak stress and peak strain initially increased but eventually decreased as the loading rates continued to rise. The degree of strengthening, toughening, and energy absorption capacity of concrete materials progressively decreased as the escalation of strain rate after the cooling process. Moreover, the inclusion of steel fibers proved effective in preventing cracking and damage to the concrete, preserving the integrity of specimens even at higher temperatures. Simultaneously, the residual stress and deformation capacity of SFRC showed considerable enhancement after exposure to elevated temperatures.

ObjectiveThis study aims to apply different machine learning (ML) methods to construct risk prediction models for pulmonary embolism (PE) in hospitalized patients, and to evaluate and compare the predictive efficacy and clinical benefit of each model.MethodsWe conducted a retrospective study involving 332 participants (172 PE positive cases and 160 PE negative cases) recruited from Guangdong Medical University. Participants were randomly divided into a training group (70%) and a validation group (30%). Baseline data were analyzed using univariate analysis, and potential independent risk factors associated with PE were further identified through univariate and multivariate logistic regression analysis. Six ML models, namely Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Naive Bayes (NB), Support Vector Machine (SVM), and AdaBoost were developed. The predictive efficacy of each model was compared using the receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC). Clinical benefit was assessed using decision curve analysis (DCA).ResultsLogistic regression analysis identified lower extremity deep venous thrombosis, elevated D-dimer, shortened activated partial prothrombin time, and increased red blood cell distribution width as potential independent risk factors for PE. Among the six ML models, the RF model achieved the highest AUC of 0.778. Additionally, DCA consistently indicated that the RF model offered the greatest clinical benefit.ConclusionThis study developed six ML models, with the RF model exhibiting the highest predictive efficacy and clinical benefit in the identification and prediction of PE occurrence in hospitalized patients.

Corrosion transition during uniform corrosion of zirconium alloys receives much attention since it is the major degradation procedure. However, predicting the time and oxide thickness at transition has been hindered by the lack of knowledge about transition kinetics and how it responds to varied temperatures. Current study investigated the temperature-sensitivity of corrosion kinetics, transition behavior and microstructures of various zirconium alloys corroded in superheated steam ranging from 390 °C/10.3 MPa to 455 °C/10.3 MPa by autoclave experiment and microscopy analyses. Transition time was found to follow Arrhenius-type relationship with temperature for the first time. Both the transition oxide thickness and metastable oxide thickness increased with temperature, which was theoretically deduced and experimentally confirmed. In Zr-4 oxides, a transition thickness varying from 3.3 μm at 390 °C to 4.2 μm at 455 °C was observed. Microstructure results presented rather large HCP-ZrO particles (200∼400 nm) at O/M interface and they were even larger at the protruded positions. An intense sub-stoichiometric atmosphere was identified at O/M interface, promoting the growth of metastable oxides. The activation energy of transition kinetics was 86∼114 kJ/mol, which is close to diffusion activation energy of oxygen in tetragonal zirconia. A new model based on parabolic-law empirical relationship was thus proposed to predict transition kinetics. Predictions regarding the time to oxidation breakaway at 900–1000 °C were reported, and the results were in good agreement with the experimental data.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

This study assesses the morphological effectiveness of benign prostatic hyperplasia (BPH) surgery using multislice spiral computed tomography three-dimensional imaging (CT3D) with urethral contrast. Twenty-five male patients with BPH and bladder outlet obstruction (BOO) who underwent bipolar transurethral resection of the prostate were selected. Preoperative and postoperative CT3D indicators of retrograde and voiding cystourethrography, including bladder neck diameter, length of the posterior urethra, and degree of prostate protrusion into the bladder and upper and lower diameter of the prostate were used to assess bladder neck and posterior urethra morphology and BOO severity. In addition, preoperative and postoperative International Prostate Symptom Scores and maximum urine flow rates were compared. Postoperative CT3D was used to evaluate changes following obstruction relief postsurgery. Preoperative CT3D indicated significant BOO, whereas postoperative imaging showed improved patency but with irregular posterior urethral lumens and varying degrees of residual glandular tissue. Comparative analysis of preoperative and postoperative bladder outlet metrics revealed significant changes ( p < 0.05). Urethral contrast CT3D effectively visualizes the prostate, bladder neck, and prostatic urethra. It quantifies changes in the urethral lumen postsurgery, correlating the extent of posterior urethral lumen spaciousness with urinary flow rates.

Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation.

BackgroundWuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic.ObjectiveThis study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017–2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools.MethodsThis study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis.ResultsFrom 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools.ConclusionWe successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L -

Support Vector Machines (SVMs) have achieved significant success in the field of power transformer fault diagnosis. However, challenges such as determining SVM hyperparameters and their suitability for binary classification still exist. This paper proposes a novel method for power transformer fault diagnosis, called ECOC-WSO-SVM, which utilizes a White Shark Optimizer (WSO) and error correcting output codes to optimize SVMs. First, t-distributed Stochastic Neighbor Embedding (t-SNE) is employed to reduce the dimensionality of Dissolved Gas Analysis (DGA) features constructed using the correlation ratio method, from 26 dimensions. In addition, to effectively solve the hyperparameters of SVMs, a multi-strategy fusion method is proposed to improve the WSO, incorporating tent chaos initialization, elite opposite learning, and selection strategies, forming TEWSO, and its superior optimization performance is validated using IEEE CEC2021 test functions. Furthermore, to address the limitations of SVMs as a binary classifier, an error correcting output code fusion SVM is introduced, thus constructing a multi-class SVM model. Finally, the diagnostic performance of the ECOC-TEWSO-SVM model is validated using real-world data. Results demonstrate that the proposed model exhibits the best diagnostic performance compared to traditional models and those in the literature, thereby proving the significance and effectiveness of the proposed model.

In this article, the dynamics of a seven degrees of freedom robot with a telescopic forearm for the spray-painting of large workpiece is investigated. A novel two-step inverse kinematic solving method that combines numerical and analytical approaches is proposed to solve the inverse kinematics of the seven degrees of freedom robot with two redundant degrees of freedom for spray-painting applications. Based on the kinematic model, the dynamic model is derived using the Newton–Euler method. For the dynamic parameter identification, the dynamic model is written in a linear form with respect to dynamic parameters. Considering the effect of the telescopic forearm on the dynamics of the robot, two novel performance indices concerning the inertial load and gravitational load in the joint space are proposed to evaluate the effect of the telescopic forearm on the dynamic load of the robot. Monte Carlo method is used to solve these two indices. This work is essential for the motion planning and control of the seven degrees of freedom spray-painting robot with a telescopic forearm.

IntroductionThis study aims to evaluate the qualifications and identify skill enhancement areas for epidemiological investigators in Centers for Disease Control and Prevention (CDCs) in Guizhou’s, informing future training and policy initiatives to strengthen public health responses.MethodsA cross-sectional survey was conducted in August 2022, and an online, self-designed questionnaire on the Epidemiological Dynamic Data Collection platform was administered to evaluate the professional staff in CDCs. The responses were scored and presented using descriptive statistical methods, and the factors influencing the total score were analyzed by one-way ANOVA and linear regression.Results and discussionA total of 1321 questionnaires were collected, yielding an average score of 14.86±3.49 and a qualification rate of 29.9%. The scoring rate of ability of individual protection and coordination in epidemic control was high (87.25%). Meanwhile, improvements in further training were needed in areas such as data analysis ability (23.67%), knowledge of site disinfection (40.40%), and epidemiological investigation skills (42.50%). No significant difference was observed between the scores of city and county CDCs, (t = 1.071, p =0.284). The effects of gender and age could be disregarded, and the experience in epidemiological work and training (including investigation on COVID-19 cases and contacts), educational background, and professional title partially explained the survey outcome (R Square of the linear regression model was 0.351). The survey indicated the need for additional well-trained epidemiologic investigators in Guizhou. Specified training was effective in improving epidemiologic investigation, and enhancement in data analysis ability and knowledge of field disinfection are recommended in professional staff cultivation.

ABSTRACTEsophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

Nonreciprocal radiation, violating Kirchhoff’s law, has sparked significant interest due to its potential in energy conversion and capture technologies. In this paper, we introduce a hybrid structure combining graphene and Weyl semimetal to achieve tunable dual-channel nonreciprocal radiation through guided mode resonances. This structure overcomes the limitations of traditional single-channel systems by offering dual-channel nonreciprocal radiation, enhanced efficiency, and increased flexibility. The structure exhibits excellent wide-angle nonreciprocal characteristics. Furthermore, by investigating the impact of structural parameters, the structure demonstrates large parameter tolerance, facilitating practical fabrication. Finally, leveraging the tunable properties of graphene, we showcase the linear control behavior of the system. Our findings pave the way for advanced energy-harvesting and conversion structures in advanced thermal systems.