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Introduction: Golden pompano (Trachinotus ovatus) is economically significant important for offshore cage aquaculture in China and Southeast Asian countries. Lack of high-quality genomic data and accurate gene annotations greatly restricts its genetic breeding progress. Objectives: To decode the mechanisms of sex determination and rapid growth in golden pompano and facilitate the sex- and growth-aimed genetic breeding. Methods: Genome assemblies of male and female golden pompano were generated using Illumina, PacBio, BioNano, genetic maps and Hi-C sequencing data. Genomic comparisons, whole genome re-sequencing of 202 F1 individuals, QTL mapping and gonadal transcriptomes were used to analyze the sex determining region, sex chromosome evolution, SNP loci, and growth candidate genes. Zebrafish model was used to investigate the functions of growth candidate gene. Results: Female (644.45 Mb) and male (652.12 Mb) genomes of golden pompano were assembled and annotated at the chromosome level. Both genomes are highly conserved and no new or highly differentiated sex chromosomes occur. A 3.5 Mb sex determining region on LG15 was identified, where Hsd17b1, Micall2 and Lmx1a were putative candidates for sex determination. Three SNP loci significantly linked to growth were pinpointed, and a growth-linked gene gpsstr1 was identified by locus BSNP1369 (G → C, 17489695, Chr23). Loss of sstr1a (homologue of gpsstr1) in zebrafish caused growth retardation. Conclusion: This study provides insights into sex chromosome evolution, sex determination and rapid growth of golden pompano.

Abstract To overcome the limitation of a single classification model’s inability to simultaneously identify multiple lesion targets within periapical radiographs, This study proposes YoCNET (Yolov5 + ConvNeXt), a novel deep learning integrated model. YoCNET leverages the target detection capability of Yolov5 and the image classification capability of ConvNeXt to achieve automatic segmentation of individual teeth and concurrent detection of periapical lesions across multiple teeth. A dataset of 1,305 periapical radiographs was used to train and validate the ConvNeXt and ResNet34 models, with an 8:2 split for training and validation. Deciduous teeth were excluded from the dataset. Furthermore, 717 individual teeth images were extracted from 200 previously unused periapical radiographs for integrated model validation. Evaluation metrics included accuracy, precision, sensitivity, F1 score, AUC (Area Under Curve), and a confusion matrix.The YoCNET integrated model demonstrated values of 90.93%, 98.88%, 85.30%, 0.9159, and 0.9757 for accuracy, precision, sensitivity, F1 score, and AUC, respectively. These metrics were superior to those achieved by the YoRNET (Yolov5 + ResNet34) integrated model, which recorded 80.47%, 83.78%, 82.16%, 0.8296, and 0.8822. The integrated model achieved high accuracy and efficiency in automatic teeh segmentation by Yolov5 and in automatically detecting multiple periapical lesions by ConvNeXt. YoCNET exhibited superior overall data performance, making it a more suitable deep learning integrated model for clinical applications.

Abstract Aiming at the Terrestrial Water Storage(TWS) changes in the Amazon River basin, this article uses the coordinate time series data of the Global Navigation Satellite System (GNSS), adopts the Variational Mode Decomposition and Bidirectional Long and Short Term Memory(VMD-BiLSTM) method to extract the vertical crustal deformation series, and then adopts the Principal Component Analysis(PCA) method to invert the changes of terrestrial water storage in the Amazon Basin from July 15, 2012 to July 25, 2018. Then, the GNSS inversion results were compared with the equivalent water height retrieved from Gravity Recovery and Climate Experiment (GRACE) data. The results show that (1) the extraction method proposed in this article has better denoising effect than the traditional method; (2) the surface hydrological load deformation can be well calculated using GNSS coordinate vertical time series, and then the regional TWS changes can be inverted, which has a good consistency with the result of GRACE inversion of water storage, and has almost the same seasonal variation characteristics; (3) There is a strong correlation between TWS changes retrieved by GNSS based on surface deformation characteristics and water mass changes calculated by GRACE based on gravitational field changes, but GNSS satellite’s all-weather measurement results in a finer time scale compared with GRACE inversion results. In summary, GNSS can be used as a supplementary technology for monitoring terrestrial water storage changes, and can complement the advantages of GRACE technology.

Objective This study aimed to identify and characterize a novel endo-β-glucanase, IDSGLUC9-4, from the rumen metatranscriptome of Hu sheep. Methods A novel endo-β-glucanase, IDSGLUC9-4, was heterologously expressed in Escherichia coli and biochemically characterized. The optimal temperature and pH of recombinant IDSGLUC9-4 were determined. Subsequently, substrate specificity of the enzyme was assessed using mixed-linked glucans including barley β-glucan and Icelandic moss lichenan. Thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), matrix assisted laser desorption ionization time of flight mass spectrometry analyses were conducted to determine the products released from polysaccharides and cello-oligosaccharides substrates. Results The recombinant IDSGLUC9-4 exhibited temperature and pH optima of 40°C and pH 6.0, respectively. It exclusively hydrolyzed mixed-linked glucans, with significant activity observed for barley β-glucan (109.59±3.61 μmol/mg min) and Icelandic moss lichenan (35.35±1.55 μmol/mg min). TLC and HPLC analyses revealed that IDSGLUC9-4 primarily released cellobiose, cellotriose, and cellotetraose from polysaccharide substrates. Furthermore, after 48 h of reaction, IDSGLUC9-4 removed most of the glucose, indicating transglycosylation activity alongside its endo-glucanase activity. Conclusion The recombinant IDSGLUC9-4 was a relatively acid-resistant, mesophilic endo-glucanase (EC 3.2.1.4) that hydrolyzed glucan-like substrates, generating predominantly G3 and G4 oligosaccharides, and which appeared to have glycosylation activity. These findings provided insights into the substrate specificity and product profiles of rumen-derived GH9 glucanases and contributed to the expanding knowledge of cellulolytic enzymes and novel herbivore rumen enzymes in general.

Identifying novel compound–protein interactions (CPIs) plays a pivotal role in target identification and drug discovery. Although the recent multimodal methods have achieved outstanding advances in CPI prediction, they fail to effectively learn both intra-modality and inter-modality dynamics, which limits their prediction performance. To address the limitation, we propose a novel multimodal tensor fusion CPI prediction framework, named MMTF-CPI, which contains three unimodal learning modules for structure, heterogeneous network and transcriptional profiling modalities, a tensor fusion module and a prediction module. MMTF-CPI is capable of focusing on both intra-modality and inter-modality dynamics with the tensor fusion module. We demonstrated that MMTF-CPI is superior to multiple state-of-the-art multimodal methods across seven datasets. The prediction performance of MMTF-CPI is significantly improved with the tensor fusion module compared to other fusion methods. Moreover, our case studies confirmed the practical value of MMTF-CPI in target identification. Via MMTF-CPI, we also discovered several candidate compounds for the therapy of breast cancer and non-small cell lung cancer.

Abstract Background Health lifestyles exert a substantial influence on the quality of everyday life, primarily affecting health maintenance and enhancement. While health-related practices during the COVID-19 pandemic may have positively altered the health lifestyles of Canadians to a certain degree, government reports indicate that issues related to health behaviors, such as cigarette smoking, physical inactivity, and alcohol consumption, continue to pose challenges to the health of Canadians. Social determinants of these health behaviors thus hold significant academic value in the formulation of policy guidelines. Objective The aim of this study is to scrutinize the social determinants of health with respect to social factors that have may have impacts on the health-related behaviors of Canadians. We tested health behaviors including cigarette use, alcohol consumption, and participation in physical exercise, which are integral to the promotion and improvement of individual health. Methods To examine the social determinants of Canadians’ health lifestyles, we utilized nationally representative data from the 2017–2018 Canadian Community Health Survey annual component. Our data analysis involved the bootstrapping method with two-level mixed-effect logistic regressions, ordered logistic regressions, and negative binomial regressions. Additionally, we conducted several robustness checks to confirm the validity of our findings. Results The findings show that demographic background, socioeconomic status, social connections, and physical and mental health conditions all play a role in Canadians’ smoking, physical activity, and drinking behaviors. Noticeably, the association patterns linking to these social determinants vary across specific health lifestyles, shedding light on the complex nature of the social determinants that may influence young and middle-aged Canadians’ health lifestyles. Moreover, in the context of Canada, the health-region level demographic, socioeconomic, and working conditions are significantly linked to residents’ health lifestyles. Conclusions Investigating the social determinants of health lifestyles is pivotal for policymakers, providing them with the necessary insights to create effective interventions that promote healthy behaviors among specific demographic groups. It is recommended that health education and interventions at the community level targeting smoking, physical inactivity, and alcohol consumption be introduced. These interventions should be tailored to specific subgroups, considering their demographic and socioeconomic characteristics, social networks, and health status. For instance, it is imperative to focus our attention on individuals with lower educational attainment and socioeconomic status, particularly in relation to their smoking habits and physical inactivity. Conversely, interventions aimed at addressing alcohol consumption should be targeted towards individuals of a higher socioeconomic status. This nuanced approach allows for a more effective and tailored intervention strategy.

In this study, aiming at fulfilling the requirement of polarization acquisition and utilization, a method for active deception jamming recognition based on the time-varying polarization-conversion metasurface is investigated. First, an anisotropic phase-modulated metasurface supporting 3-bit phase quantization in the 9.6～10.1 GHz frequency band is designed. By optimizing the periodical phase coding, the polarization state can be converted on demand. And then, loading the polarization-conversion metasurface on a single polarization radar antenna so that the polarization states of the antenna can change along a specific trajectory. By extracting the difference in the polarization domain between target and active deception jamming, the active deception jamming could be distinguished from the radar echo. The simulation results show that under the constraints of three different polarization trajectories, the active deception jamming and targets exhibit a significant clustering effect, and the identification effect is stable. Compared with jamming identification methods that rely on dual-polarization or full-polarization radar systems, the proposed method has both low cost and high efficiency, which has great application potential in radar anti-jamming.

Abstract Background In plants, the leaf functions as a solar panel, where photosynthesis converts carbon dioxide and water into carbohydrates and oxygen. In soybean, leaf type traits, including leaf shape, leaf area, leaf width, and leaf width so on, are considered to be associated with yield. In this study, we performed morphological characterization, transcriptome analysis, and endogenous hormone analysis of a rolled and narrow leaf mutant line (rl) in soybean. Results Compared with wild type HX3, mutant line rl showed rolled and narrower leaflet, and smaller leaf, meanwhile rl also performed narrower pod and narrower seed. Anatomical analysis of leaflet demonstrated that cell area of upper epidermis was bigger than the cell area of lower epidermis in rl, which may lead rolled and narrow leaf. Transcriptome analysis revealed that several cytokinin oxidase/dehydrogenase (CKX) genes (Glyma.06G028900, Glyma.09G225400, Glyma.13G104700, Glyma.14G099000, and Glyma.17G054500) were up-regulation dramatically, which may cause lower cytokinin level in rl. Endogenous hormone analysis verified that cytokinin content of rl was lower. Hormone treatment results indicated that 6-BA rescued rolled leaf enough, rescued partly narrow leaf. And after 6-BA treatment, the cell area was similar between upper epidermis and lower epidermis in rl. Although IAA content and ABA content were reduced in rl, but exogenous IAA and ABA didn’t affect leaf type of HX3 and rl. Conclusions Our results suggest abnormal cytokinin metabolism caused rolled and narrow leaf in rl, and provide valuable clues for further understanding the mechanisms underlying leaf development in soybean.

Abstract Oxytetracycline (OTC) and ciprofloxacin (CIP) contamination have caused serious risks to human health, and modified biochar is considered as a potential adsorbent for their removal. The typical agricultural waste of cotton husk was used as the feedstock, then was combined with γ-Fe2O3 and ball milling to innovatively synthesize nano zero-valent iron (nZVI) supporting magnetic cotton hush-derived biochar (Fe2O3@BMBC) by reductive calcination. Fe2O3@BMBC performed excellent adsorption performance with a maximum adsorption capacity for OTC (266.7 mg·g−1) and CIP (83.36 mg·g−1), and its adsorption capacity was 1.6 and 2.3 times that of cotton husk biochar (BC). Characterization analysis showed that Fe2O3@BMBC contained abundant oxygenated functional groups (e.g., -OH, C = O and Fe–O) and its surface was covered by diverse iron oxides. The high magnetization sensitivity of Fe2O3@BMBC guaranteed that it was easily to be separated by a magnet. Oxygenated functional groups (e.g., -OH, C = O and Fe–O) participated in the adsorption process, and solution pH significantly affected the adsorption behaviour, and pseudo-second-order model and Freundlich model better fitting the kinetics and isotherms data. These results confirmed that π-π conjugation, H-bonding, Fe–O complexation and electrostatic interactions contributed to the greater adsorption capacity of Fe2O3@BMBC. Ethanol + ultrasound could efficiently regenerate the used Fe2O3@BMBC and maintain its sustainable adsorption performance for OTC and CIP. Additionally, Fe2O3@BMBC performed a good environmental security in a wide pH range (from 3 to 11) in view of the low leaching risk of Fe. Graphical Abstract

Infrastructure and economic networks can be used to describe different dimensions of urban systems, and a close relationship exists between them. Therefore, it is important to study the dynamic coupling relationship between them to promote the formation and development of urban networks. Relevant studies have compared and analyzed the evolution characteristics of urban network structures from different dimensions; however, relatively few studies have focused on the dynamic coupling relationship between high-speed rail and remote investment networks. The formation and development of high-speed rail networks has become a key factor affecting remote investment networks, and the layout of a remote investment network also affects the development of a high-speed rail network. To this end, we used high-speed railway operation service data and related transaction data of listed companies from 2008 to 2023 to construct high-speed railway and remote investment networks reflecting intercity high-speed railway and enterprise remote investment connections, respectively. QAP correlation analysis was used to explore the overall correlation between the two networks. Using the quadrantal diagram method and the coupling coordination degree model, we discuss the spatiotemporal coupling coordination of the two networks, identify the types of cities and urban connections, and propose operational planning suggestions for cities and high-speed railways. The results indicate the following: 1) Both the scale and density of the high-speed rail network and the off-site investment network show a rapid growth trend, and the expansion of the high-speed rail network is significantly faster than that of the off-site investment network. There is a significant positive correlation between high-speed rail and the remote investment network as a whole, and the degree of correlation first increases and then decreases. 2) In terms of space, cities with the simultaneous development of high-speed rail and remote investment networks are primarily concentrated in the administrative and economic centers of the eastern region. However, cities with lagging high-speed rail networks are mainly located in non-transportation hub cities in the economically developed areas of the Pearl River Delta, Dalian, and Urumqi. Moreover, cities with advanced high-speed rail networks are mainly centered in the central and eastern regions around the main high-speed rail lines. 3) Cities with synchronous development of high-speed rail and remote investment networks are mainly located in developed cities within the five major urban agglomerations. The pairs of cities with lagging high-speed rail networks are mainly located between the core cities of different urban agglomerations. Pairs of cities with advanced high-speed rail networks are typically positioned between cities that are closer together and contain at least one city with a less developed economy. The relevant research results can provide policy support for China's high-speed rail operation planning and urban system construction.

Abstract The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p

Abstract Purpose To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey. Methods In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings. Results After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

Abstract Members of the multiple antibiotic resistance regulator (MarR) protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance. MarR family proteins function as repressors, and their interactions with modulators induce the expression of controlled genes. The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins. However, recently, several MarR family proteins have been reported to sense sulfane sulfur, including zero‐valent sulfur, persulfide (R‐SSH), and polysulfide (R‐SnH, n ≥ 2). Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth. The changing levels of sulfane sulfur affect the expression of many MarR‐controlled genes. Sulfane sulfur reacts with the cysteine thiols of MarR family proteins, causing the formation of protein thiol persulfide, disulfide bonds, and other modifications. Several MarR family proteins that respond to reactive oxygen species (ROS) also sense sulfane sulfur, as both sulfane sulfur and ROS induce the formation of disulfide bonds. This review focused on MarR family proteins that sense sulfane sulfur. However, the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur, which is emerging as a modulator of gene regulation.

Abstract Background The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia’nan cattle, a crossbreed of Charolais and Nanyang cattle, is China’s first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia’nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia’nan cattle using whole-genome sequencing data from 30 Xia’nan cattle and 178 published cattle genomic data. Result The ancestry estimating composition analysis showed that the ancestry proportions for Xia’nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia’nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia’nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (F ST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1). Conclusion We elucidated the genomic features and population structure of Xia’nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia’nan cattle. This research provided a basis for further breeding improvements in Xia’nan cattle and served as a reference for genetic enhancements in other crossbreed cattle.

Abstract Background Immune checkpoint inhibitors are a relatively new advancement in the world of cancer therapy. As such, their adverse effects have yet to be fully understood, with only recent literature documenting autoimmune phenomena secondary to their utilization. Specific immune checkpoint inhibitors have recently been linked with the development of myasthenia gravis, which is classically known to manifest spontaneously in patients. Given the relative rarity of this presentation, the risk of misdiagnosis and subsequent mortality and morbidity is concerning. Case presentation We discuss the case of a 73-year-old male who presented with clinical symptoms of myasthenia gravis and myositis shortly after beginning treatment with Pembrolizumab. The diagnosis of myasthenia gravis was initially missed at an outside hospital, which delayed initiation of proper treatment. Conclusion While the incidence of “de-novo” diseases secondary to immune checkpoint inhibitors might be increasing, guidelines regarding best treatment options do not yet exist, leaving many providers at a loss when faced with making clinical decisions surrounding patients with De novo myasthenia gravis. Thus, our goal is to underscore the importance of early recognition of this disease, and emphasize the need for a standard of care as immune checkpoint inhibitors usage becomes more prevalent.

Fine particulate matter (PM2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM2.5 constituents during the year before the month of hormone testing. Relationships between PM2.5 constituents [organic matter (OM), chloride (Cl-), sulfate (SO42-), ammonium (NH4+), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl- and NH4+ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl- were associated with −7.27 % (-9.34 %, −5.16 %) and −8.52 % (-10.99 %, −5.98 %) decreases in progesterone, and per IQR increment in SO42- was associated with a −9.15 % (-10.31 %, −7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM2.5 pollution reduction strategies that could benefit women's reproductive health.

Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research.

ABSTRACT: Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

PurposeAccurate preoperative identification of Human epidermal growth factor receptor 2 (HER2) low expression breast cancer (BC) is critical for clinical decision-making. Our aim was to use machine learning methods to develop and validate an ultrasound-based radiomics nomogram for predicting HER2-low expression in BC.MethodsIn this retrospective study, 222 patients (108 HER2-0 expression and 114 HER2-low expression) with BC were included. The enrolled patients were randomly divided into a training cohort and a test cohort with a ratio of 8:2. The tumor region of interest was manually delineated from ultrasound image, and radiomics features were subsequently extracted. The features underwent dimension reduction using the least absolute shrinkage and selection operator (LASSO) algorithm, and rad-score were calculated. Five machine learning algorithms were applied for training, and the algorithm demonstrating the best performance was selected to construct a radiomics (USR) model. Clinical risk factors were integrated with rad-score to construct the prediction model, and a nomogram was plotted. The performance of the nomogram was assessed using receiver operating characteristic curve and decision curve analysis.ResultsA total of 480 radiomics features were extracted, out of which 11 were screened out. The majority of the extracted features were wavelet features. Subsequently, the USR model was established, and rad-scores were computed. The nomogram, incorporating rad-score, tumor shape, border, and microcalcification, achieved the best performance in both the training cohort (AUC 0.89; 95%CI 0.836-0.936) and the test cohort (AUC 0.84; 95%CI 0.722-0.958), outperforming both the USR model and clinical model. The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram.ConclusionThe nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek’s disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

ObjectiveTo investigate the clinical utility of Next Generation Sequencing (NGS) in molecular typing of endometrial carcinoma and its combined screening for Lynch Syndrome (LS).Methods90 patients diagnosed with endometrial carcinoma (EC) and receiving treatment at the Third Affiliated Hospital of Zhengzhou University between March 2022 and December 2023 were included in this study. Molecular typing and germline evaluation for LS were conducted using NGS on the Illumina platform. A retrospective analysis was performed to examine the clinical pathological characteristics, molecular mutation spectrum, and LS screening outcomes among patients with four distinct molecular subtyping categories.ResultsAmong the 90 cases of EC, 11 cases (12.2%) of POLE mut type, 19 cases (21.1%) of MMRd type, 6 cases (6.7%) of p53 abn type, and 54 cases (60%) of NSMP type were detected, with detailed analysis of their respective molecular characteristics. LS screening identified 9 cases (10%) of pathogenic germline mutations in MMR genes, including 3 cases of MLH1 germline mutations, 2 cases of PMS2, 2 of MSH2, and 2 of MSH6. Of the 9 LS patients, 7 were MMRd type and 2 NSMP type, with 7 cases showing abnormal MMR protein expression. Additionally, 6 cases with germline variants of uncertain significance in MMR genes were detected, including 2 MLH1, 1 MSH6, 2 MSH6, 1 PMS2, and 1 EPCAM.ConclusionNGS enables precise molecular typing of endometrial carcinoma through the identification of mutations in the POLE, TP53, and MMR genes. Conducting germline mutation testing for MMR genes in all patients with endometrial carcinoma can effectively prevent instances of overlooked LS diagnoses. Nevertheless, the extensive expenses associated with NGS necessitate additional validation and investigation before its clinical implementation can be fully endorsed.

Abstract Holothuria scabra, a commercially valuable yet ecologically vulnerable tropical holothuroid, has experienced a severe decline in its wild populations, especially in China. Genomic resources are crucial for the development of effective genomic breeding projects and stock conservation strategies to restore these natural populations. Until now, a high-quality, chromosome-level reference genome for H. scabra has not been available. Here, we employed Oxford Nanopore and Hi-C sequencing technologies to assemble and annotate a high-quality, chromosome-level reference genome of H. scabra. The final genome comprised 31 scaffolds with a total length of 1.19 Gb and a scaffold N50 length of 53.52 Mb. Remarkably, 1,191.67 Mb (99.95%) of the sequences were anchored to 23 pseudo-chromosomes, with the longest one spanning 79.75 Mb. A total of 34,418 protein-coding genes were annotated in the final genome, with BUSCO analysis revealing 98.01% coverage of metazoa_odb10 genes, marking a significant improvement compared to the previous report. These chromosome-level sequences and annotations will provide an essential genomic basis for further investigation into molecular breeding and conservation management of H. scabra.

Abstract Background Growth rate is a crucial economic trait for farmed animals, but the genetic regulation of this trait is largely unknown in non-model organisms such as shrimp. Results In this study, we performed genome-wide phenotypic quantitative trait loci (QTL) and expression quantitative trait loci (eQTL) mapping analyses to identify genes affecting the growth rate of Pacific white shrimp (Litopenaeus vannamei), which is the most commercially-farmed crustacean worldwide. We used RNA-sequencing of 268 individuals in a mapping population, and subsequently validated our findings through gene silencing and shrimp growth experiments. We constructed a high-density genetic linkage map comprising 5533 markers spanning 44 linkage groups, with a total distance of 6205.75 cM and an average marker interval of 1.12 cM. Our analyses identified 11 QTLs significantly correlated with growth rate, and 117,525 eQTLs. By integrating QTL and eQTL data, we identified a gene (metalloreductase STEAP4) highly associated with shrimp growth rate. RNA interference (RNAi) analysis and growth experiments confirmed that STEAP4 was significantly correlated with growth rate in L. vannamei. Conclusions Our results indicate that the comprehensive analysis of QTL and eQTL can effectively identify genes involved in complex animal traits. This is important for marker-assisted selection (MAS) of animals. Our work contributes to the development of shrimp breeding and available genetic resources.

Abstract Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06–73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.

Abstract Background Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments. Methods Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A protein‒protein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot. Results A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-β-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins. Conclusions AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.

Abstract It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Abstract Metamaterials composed of different geometrical primitives have different properties. Corresponding to the fundamental geometrical forms of line, plane, and surface, beam-, plate-, and shell-based lattice metamaterials enjoy many advantages in many aspects, respectively. To fully exploit the advantages of each structural archetype, we propose a multilayer strategy and topology optimization technique to design lattice metamaterial in this study. Under the frame of the multilayer strategy, the design space is enlarged and diversified, and the design freedom is increased. Topology optimization is applied to explore better designs in the larger and diverse design space. Beam-plate-shell-combined metamaterials automatically emerge from the optimization to achieve ultrahigh stiffness. Benefiting from high stiffness, energy absorption performances of optimized results also demonstrate substantial improvements under large geometrical deformation. The multilayer strategy and topology optimization can also bring a series of tunable dimensions for lattice design, which helps achieve desired mechanical properties, such as isotropic elasticity and functionally grading material property, and superior performances in acoustic tuning, electrostatic shielding, and fluid field tuning. We envision that a broad array of synthetic and composite metamaterials with unprecedented performance can be designed with the multilayer strategy and topology optimization.

The sustainable recovery and utilization of sludge bioenergy within a circular economy context has drawn increasing attention, but there is currently a shortage of reliable technology. This study presents an innovative biotechnology based on free nitrous acid (FNA) to realize sustainable organics recovery from waste activated sludge (WAS) in-situ, driving efficient nitrogen removal from ammonia rich mature landfill leachate by integrating partial nitrification, fermentation, and denitrification process (PN/DN–F/DN). First, ammonia ((1708.5 ± 142.9) mg·L−1) in mature landfill leachate is oxidized to nitrite in the aerobic stage of a partial nitrification coupling denitrification (PN/DN) sequencing batch reactor (SBR), with nitrite accumulation ratio of 95.4% ± 2.5%. Then, intermediate effluent (NO2−–N = (1196.9 ± 184.2) mg·L−1) of the PN/DN-SBR, along with concentrated WAS (volatile solids (VSs) = (15 119.8 ± 2 484.2) mg·L−1), is fed into an anoxic reactor for fermentation coupling denitrification process (F/DN). FNA, the protonated form of nitrite, degrades organics in the WAS to the soluble fraction by the biocidal effect, and the released organics are utilized by denitrifiers to drive NOx− reduction. An ultra-fast sludge reduction rate of 4.89 kg·m−3·d−1 and nitrogen removal rate of 0.46 kg·m−3·d−1 were realized in the process. Finally, F/DN-SBR effluent containing organics is refluxed to PN/DN-SBR for secondary denitrification in the post anoxic stage. After 175 d operation, an average of 19 350.6 mg chemical oxygen demand organics were recovered per operational cycle, with 95.2% nitrogen removal and 53.4% sludge reduction. PN/DN–F/DN is of great significance for promoting a paradigm transformation from energy consumption to energy neutral, specifically, the total benefit in equivalent terms of energy was 291.8 kW·h·t−1 total solid.

Abstract To examine the disparity in deformation behavior and mechanical qualities between anchor cables with C-shaped tubes and regular anchor cables under shear conditions. The double-sided shear tests of free-section anchor cables and anchor cables with C-shaped tubes were conducted utilizing the indoor large-scale double-shear test equipment with varying pretension loads. The indoor double-shear tests indicate that the inclusion of the C-shaped tube alters the stress distribution of the anchor cables inside the anchor cables with C-shaped tubes and mitigates the impact of stress concentration. Moreover, it facilitates the transition of the anchor cable's failure mode from a mix of tensile and shear breaking to mainly tensile breakage. In addition, ABAQUS finite element analysis software was used to establish a double shear test model of the anchor cable with C-shaped tube to accurately simulate the interaction and stress distribution among the anchor cable, C-shaped tube, and concrete block in the double shear test. The findings of the simulation results reveal that the numerical model can adequately depict the evolution of the stress distribution in the prestressed anchored structure and the damage of the concrete block with increasing shear displacement. The relational equation for the yield state of the anchor cable with C-shaped tube under combined tensile and shear loads is found by integrating the experimental and simulation data, the static beam theory, and the concept of minimal potential energy.

Abstract This article studies a distributed consensus‐based estimation problem for discrete time‐varying non‐linear systems with missing measurements and Denial of Service (DoS) attacks. The probability of missing measurements is independent for each sensor. The communication link between sensor nodes is unreliable and subjected to DoS attacks. To achieve accurate state estimation against missing measurements, a local estimator with compensation mechanism is designed for each sensor node. A stochastic event‐triggered mechanism is used to lessen additional information transfer. Based on this, a distributed consensus‐based estimator is constructed by continually fusing local neighbours information matrixs and vectors. Moreover, the analysis of the designed estimator boundedness is presented. Finally, the effectiveness of the proposed algorithm is verified by three numerical examples.

The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor cells. The pro-death effect of Nur77 can be regulated by its interaction with Bcl-2, resulting in conversion of Bcl-2 from a survival to killer. As Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy, targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer therapeutics. Here, we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 pathway. In vitro and animal studies revealed an apoptotic effect of XS561 in a range of tumor cell lines including MDA-MB-231 triple-negative breast cancer (TNBC) and MCF-7/LCC2 tamoxifen-resistant breast cancer (TAMR) in a Nur77-dependent manner. Mechanistic studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria, resulting in mitochondria-related apoptosis. Interestingly, XS561-induced accumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 condensates. Together, our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in mediating the apoptotic effect of Nur77 at mitochondria.

Abstract The cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2’s contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2’s novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation. AIM2-deficient aged mice exhibited heightened lipid accumulation and hepatic triglycerides in comparison to their wild-type counterparts. Strikingly, AIM2 knockout mice subjected to APAP overdose demonstrated intensified liver injury, compromised mitochondrial stability, exacerbated glutathione depletion, diminished autophagy, and elevated levels of phosphorylated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, our investigation revealed AIM2’s mitochondrial localization; its overexpression in mouse hepatocytes amplified autophagy while dampening JNK phosphorylation. Notably, induction of autophagy through rapamycin administration mitigated serum alanine aminotransferase levels and reduced the necrotic liver area in AIM2-deficient aged mice following APAP overdose. Mechanistically, AIM2 deficiency exacerbated APAP-induced acute liver damage and inflammation in aged mice by intensifying oxidative stress and augmenting the phosphorylation of JNK and ERK. Given its regulatory role in autophagy and lipid peroxidation, AIM2 emerges as a promising therapeutic target for age-related acute liver damage treatment.

Selenomethionine (SeMet) is a beneficial organic source of selenium that is extensively used as a food additive owing to its antioxidant and anti-inflammatory properties. Due to the sensitivity of the kidneys to noxious stimuli, they are more susceptible to various injuries. To investigate the protective mechanisms of SeMet supplementation against kidney injury, we established an in vivo experimental model using laying hens treated with SeMet (0.5 mg/kg diet) and/or lipopolysaccharide (LPS) (0.2 mg/kg. BW) and an in vitro model of chicken embryo primary kidney (CEK) cells treated with SeMet (0.075 mM) and with/ without LPS (60 μg/mL). SeMet treatment alleviated the LPS-induced kidney insufficiency and mitochondrial damage. Furthermore, it reduced the expression of TLR4, RIPK3, MLKL, DRP1, NLRP3, and IL-1β in the kidneys of laying hens. RIPK3 is known to induced necroptosis and inflammation by activating of the downstream factors DRP1 and MLKL. To investigate the mechanism whereby SeMet alleviates LPS-induced necroptosis in the kidney, we pretreated CEK cells with TLR4, RIPK3, and DRP1 inhibitors. The results demonstrated that RIPK3 inhibition resulted in a significantly increased in the mitochondrial membrane potential and downregulation of DRP1. Upon the inhibition of DRP1 expression, MLKL, NLRP3, and IL-1β expression also decreased. In summary, SeMet regulates the TLR4/RIPK3/DRP1 signaling pathway to restore the LPS-induced imbalances in mitochondrial dynamics, thereby alleviating necroptosis and inflammation in the kidneys of laying hen. Selenium also increases the expression of selenoproteins. This study provides valuable information for the development of new therapeutic strategies using SeMet to alleviate kidney injury.

Roof openings are typically fitted to naturally ventilated dairy building (NVDB) for better ventilation but their impact on air pollutant emission calculations has not been fully considered. Particulate matter (PM) emission rate (ER) for NVDB rely on the total ventilation rate (VR), outdoor PM concentration and average indoor PM concentration sampled either under the roof (Roof Sampling) or in the cubicle area (Cubicle Sampling), which may show large deviations due to its spatiotemporal variation of PM concentrations and complex airflow patterns. This study utilised a novel ER calculation method (Joint Sampling) that computes the respective emission from the roof and sidewall openings by matching each outlet's VR and PM concentration. By year-round field measurements of PM2.5 and the total suspended particulates (TSP), results showed that annual average ERs of PM2.5 and TSP were 10.8 mg h−1 cow−1 and 45.7 mg h−1 cow−1 for Roof Sampling, 12.7 mg h−1 cow−1 and 40.7 mg h−1 cow−1 for Cubicle Sampling, and 11.7 mg h−1 cow−1 and 45.9 mg h−1 cow−1 for Joint Sampling. Considering the Joint Sampling results were relatively true, Roof Sampling exhibited a maximum underestimate of PM2.5 emissions of 20.8% when sidewall curtains were fully opened, whilst Cubicle Sampling demonstrated a maximum overestimate of TSP of 10.2% when the aperture was closed. Using Joint Sampling, the roof opening contributed 39.3% and 24.4% of the annual PM2.5 and TSP emissions. When sidewall openings are partially or fully closed, the Joint Sampling calculation is preferable to estimate the ER of PM.

ABSTRACTHepatitis B virus (HBV) infection remains a major public health problem and, in associated co-infection with hepatitis delta virus (HDV), causes the most severe viral hepatitis and accelerated liver disease progression. As a defective satellite RNA virus, HDV can only propagate in the presence of HBV infection, which makes HBV DNA and HDV RNA the standard biomarkers for monitoring the virological response upon antiviral therapy, in co-infected patients. Although assays have been described to quantify these viral nucleic acids in circulation independently, a method for monitoring both viruses simultaneously is not available, thus hampering characterization of their complex dynamic interactions. Here, we describe the development of a dual fluorescence channel detection system for pan-genotypic, simultaneous quantification of HBV DNA and HDV RNA through a one-step quantitative PCR. The sensitivity for both HBV and HDV is about 10 copies per microliter without significant interference between these two detection targets. This assay provides reliable detection for HBV and HDV basic research in vitro and in human liver chimeric mice. Preclinical validation of this system on serum samples from patients on or off antiviral therapy also illustrates a promising application that is rapid and cost-effective in monitoring HBV and HDV viral loads simultaneously.

IntroductionWheat awns are crucial determinants of wheat yield due to their capacity to photosynthesize and exchange gas. Understanding the genetic basis of awn length (AL) is essential for improving wheat yield in molecular breeding programs.MethodsIn this study, quantitative trait loci (QTLs) of AL were analyzed using recombinant inbred line (RIL) mapping population referred to as YY-RILs, which was derived from a cross between Yannong 15 (YN15) and Yannong 1212 (YN1212).Results and discussionSeven putative additive QTLs and 30 pairwise epistatic QTLs for AL were identified. Among them, five novel additive QTLs (except qAl-2A and qAl-5A.2) and 30 novel pairwise epistatic QTLs were identified. qAl-5A.1 was repeatedly identified in all five environment datasets, which was considered to be one novel stable QTL for AL with minor additive effects. eqAl-2B.2-2 significantly interacted with eight loci and could be of great importance in regulating awn development. The genes associated with the major stable QTL of qAl-5A.2 and the minor stable QTL of qAl-2A were B1 and WFZP-A, respectively. Awn lengths exhibited significant genetic correlations with kernel weight and kernels per spike, which could affect grain protein content to a lesser extent. This study enhances our understanding of the genetic basis of awn development and identifies novel genes as well as markers for future genetic improvement of wheat yield.

Abstract Background The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization. Results During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Conclusion Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

BackgroundLemierre’s syndrome is a rare and serious complication of pharyngitis with an estimated annual incidence of 1 in 100,000 people worldwide. It is characterized by septic thrombophlebitis of the internal jugular vein with metastatic infection, usually after oropharyngeal infection. Rare cases of Lemierre’s syndrome have been reported to be caused by odontogenic infection.Case reportA 33-year-old male visited our hospital with symptoms of fever and sore throat for 16 days. The other symptoms included pain in his left neck and shoulder. In addition, metabolic syndrome was diagnosed based on waist circumference, diabetes, and hyperlipidemia. Fusobacterium necrophorum bacteria was detected using the metagenomic next-generation sequencing (mNGS) technique. The enhanced computerized tomography (CT) scan showed thrombosis of the left proximal jugular vein and brachiocephalic vein. Based on these observations, Lemierre’s syndrome was diagnosed. The etiology was that the fillings in the root canal tooth were lost with no blood or pain about 2 weeks before the onset. The patient recovered after treatment with antibiotics and blood purification.ConclusionLemierre’s syndrome should be evaluated for patients with fever, sore throat, and neck pain. If the loss of fillings from root canal therapy occurs, especially for those with metabolic syndrome, we should be aware of the possibility of this disease. Furthermore, the mNGS test can be used as a crucial supplementary diagnostic tool for patients with undetermined fever.

Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-β receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2′-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-β1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.

Abstract Background N6‐methyladenosine (m6A) modification is essential for modulating RNA processing as well as expression, particularly in the context of malignant tumour progression. However, the exploration of m6A modification in nasopharyngeal carcinoma (NPC) remains very limited. Methods RNA m6A levels were analysed in NPC using m6A dot blot assay. The expression level of methyltransferase‐like 14 (METTL14) within NPC tissues was analysed from public databases as well as RT‐qPCR and immunohistochemistry. The influences on METTL14 expression on NPC proliferation and metastasis were explored via in vitro as well as in vivo functional assays. Targeted genes of METTL14 were screened using the m6A and gene expression profiling microarray data. Actinomycin D treatment and polysome analysis were used to detect the half‐life and translational efficiency of ANKRD22. Flow cytometry, immunofluorescence and immunoprecipitation were used to validate the role of ANKRD22 on lipid metabolism in NPC cells. ChIP‐qPCR analysis of H3K27AC signalling near the promoters of METTL14, GINS3, POLE2, PLEK2 and FERMT1 genes. Results We revealed METTL14, in NPC, correlating with poor patient prognosis. In vitro and in vivo assays indicated METTL14 actively promoted NPC cells proliferation and metastasis. METTL14 catalysed m6A modification on ANKRD22 messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency. Moreover, ANKRD22, a metabolism‐related protein on mitochondria, interacted with SLC25A1 to enhance citrate transport, elevating intracellular acetyl‐CoA content. This dual impact of ANKRD22 promoted lipid metabolism reprogramming and cellular lipid synthesis while upregulating the expression of genes associated with the cell cycle (GINS3 and POLE2) and the cytoskeleton (PLEK2 and FERMT1) through heightened epigenetic histone acetylation levels in the nucleus. Intriguingly, our findings highlighted elevated ANKRD22‐mediated histone H3 lysine 27 acetylation (H3K27AC) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC. Conclusions The identified METTL14‐ANKRD22‐SLC25A1 axis emerges as a promising therapeutic target for NPC, and also these molecules may serve as novel diagnostic biomarkers.

"Objective To investigate the application of in-hospital informatized blood glucose monitoring system (IGMS) in Jiangsu and the satisfaction of medical staff to use IGMS. Methods From August 2021 to July 2022, a survey was conducted among medical staff in 119 secondary and tertiary hospitals in Jiangsu Province. The survey included questions on the application status of IGMS, such as the year of initiation and the medical units using it, and the satisfaction with the use of IGMS in medical staff was investigated by a 5-level Likert scale. Results (1) Utilization rate of IGMS: among the 119 hospitals, 58 (48.7%) utilized IGMS. The utilization rate in Southern Jiangsu (61.0%) was significantly higher than that in Central Jiangsu (34.8%) and Northern Jiangsu (37.8%) (χ2=7.113,P=0.029). (2) Distribution of medical units using IGMS: utilization rate in internal medicine department (96.6%) was significantly higher than that in surgical department (51.7%) and ICU (39.7%) (χ2=44.550,P＜0.01), with the highest utilization rate observed in endocrinology department (96.6%). (3) Satisfaction survey: the satisfaction scale had a Cronbach's alpha of 0.702 and a KMO value of 0.742, and Bartlett's sphericity test yielded aχ2 value of 298.268 (P＜0.01). Two initial factors with eigenvalues greater than 1 accounted for 72.5% of the variance. Following a scree plot analysis, two factors were extracted ,and the items were deleted according to the reliability and validity, and the satisfaction scale containing two factors and seven items was finally determined. Ninety-seven medical staff completed the scale with a score of 29.0 (25.5, 31.0). There was no significant difference in personal satisfaction with IGMS among medical staff in different regions, hospitals of grades and titles (P＞0.05). Conclusion The utilization rate of IGMS in secondary and tertiary hospitals in Jiangsu is approximately 48.7%, with a higher rate in Southern Jiangsu. Endocrinology departments have the highest rate of IGMS usage. Medical staff are satisfied with the use of IGMS, and put forward higher expectations for the stability of networking and the standardization of training."

BackgroundFamily partial lipodystrophy (FPLD) is a rare autosomal dominant disease characterized by disorders of variable body fat loss associated with metabolic complications. FPLD6 has only been reported in a limited number of cases. Here, we reported a Chinese FPLD6 patient with compound heterozygous mutations in the lipase E, hormone-sensitive type (LIPE) gene.Case presentationA 20-year-old female patient presented with hypertriglyceridemia, diabetes mellitus, hepatomegaly, and hepatic steatosis. Subcutaneous fat was significantly diminished in her face, abdomen, and limbs. The patient was assessed by detailed clinical and biochemical examinations. A liver biopsy showed severe lipodystrophy. In addition, there were retinal changes, peripheral nerve damage, and renal tubular injury. Sequencing was performed on extracted DNA. Genetic analysis revealed that the patient had compound heterozygous mutations in the LIPE gene: c.2497_250ldel (p.Glu833LysfsTer22) and c.2705del (p.Ser902ThrfsTer27) heterozygous mutations. Verification revealed that this mutation was inherited from her father and mother, respectively, and that they formed newly discovered compound heterozygous mutations occurring in the LIPE gene, causing FPLD6.ConclusionWe reported the first case of FPLD6 in China. Gene analysis demonstrated compound heterozygous mutations in LIPE in this patient. Our case emphasizes the importance of genetic testing in young patients with severe metabolic syndromes.

IntroductionSoil microbial functional traits are key indicators of soil microbial ecological traits; however, how mixing patterns of Chinese fir and broadleaved trees drive soil microbial functional trait variation at the aggregate scale and how soil microbial functional traits are linked to soil fertility factors have largely not been determined.MethodsIn this study, soil from the 0–20 cm depths in three Chinese fir plantations was collected, and the soil samples were separated into >2 mm (large macro-aggregate), 0.25–2 mm (macro-aggregate) and

Alkali-activated slag cement (AASC) has shown immense potential for application as a low-carbon and eco-friendly cementitious material. It’s crucial to modify the AASC with superhydrophobic property to obtain excellent durability performance. In this paper, low-cost and non-toxic stearic acid (SA) is selected as a hydrophobic agent to impart integral hydrophobic property to the alkali-activated Portland slag cement mortar (AAPSCM). The SA-modified AAPSCM (M-AAPSCM) shows superhydrophobicity with a contact angle of 150.6° and a sliding angle of 9.5°, even when hammered to reveal its broken inner structure. The characterization analysis indicates that stearic acid not only successfully grafts onto the mortar surface but also forms calcium stearate, which successfully reduces the surface energy of the material. Combined with the porous rough structure constructed by medium sand and ethanol volatilization, the originally hydrophilic material achieves hydrophobic modification under the dual synergistic effect. The M-AAPSCM reached a compressive strength of 20.8 MPa after 28 days of curing, satisfying the requirements for hydraulic engineering applications. And the M-AAPSCM not only exhibits an excellent self-cleaning ability against contaminants like sand particles and chalk powder, but also demonstrates remarkable mechanical robustness, even after being subjected to blade scratching or mechanical fracture. Concurrently, the initial and final setting times of M-AAPSCM were determined to be 32 minutes and 41 minutes respectively, demonstrating its rapid-setting characteristic. Additionally, following the hydrophobic modification, AAPSCM effectively overcomes its inherent issues of severe autogenous shrinkage and poor carbonation resistance. Furthermore, when compared with the ordinary AAPSCM (O-AAPSCM), the durability of the M-AAPSCM against dry-wet cycles, icing, and freeze-thaw cycles is significantly enhanced.

As inorganic rigid waterproof materials with excellent substrate compatibility, non-toxicity, harmless, and deep penetration depth, cementitious capillary crystalline waterproof materials (CCCW) hold great potential for application in concrete structures. However, the formulations of commercially available CCCW are currently undisclosed, hindering the mechanism study of CCCW, which is not conducive to the development of more efficient and cost-effective CCCW materials. In this study, a new formulation of CCCW active chemicals was developed, consisting of calcium carbonate, sodium silicate, glycine, EDTA-4Na, and sodium acetate. The effectiveness of sodium acetate as a high-quality impermeable admixture to CCCW was explored to enhance the impermeability of the substrate. Subsequently, the fundamental performance of the coatings was subjected to further examination. After application of the coating, the impermeability and strength of the substrate were enhanced, and the fist impermeability strength reached 1.5 MPa. Micro characteristics testing indicated that the coated sample had a denser microstructure, resulting in an increase of calcium carbonate crystals and hydrated calcium silicate in the pores. The harmful pores (100–3000 nm) were transformed into less harmful or harmless pores (< 100 nm). The durability tests indicated a 12.37 % drop in carbonation area over 14 days, with an approximately 30 % drop in the Coulomb electric flux of chloride ions.

Abstract Background Reportedly, the stress–hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community‐dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all‐cause mortality in the community‐dwelling population. Methods A total of 18 480 participants were included out of 82 091 from the NHANES 1999–2014 survey. The Kaplan–Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log‐rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all‐cause mortality. A subgroup analysis was also conducted. Results A total of 3188 deaths occurred during a median follow‐up period of 11.0 (7.7; 15.4) years. The highest risk for all‐cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log‐rank p

Abstract To reduce the occurrence of information loss and distortion in image style transfer, a method is proposed for researching and designing image style transfer technology based on multi‐scale convolutional neural networks (CNNs) feature fusion. Initially, the VGG19 model is designed for coarse and fine‐scale networks to achieve multi‐scale CNN feature extraction of target image information. Subsequently, while setting the corresponding feature loss function, an additional least‐squares penalty parameter is introduced to balance the optimal total loss function. Finally, leveraging the characteristics of stochastic gradient descent iteration, image features are fused and reconstructed to obtain better style transfer images. Experimental evaluations utilize peak signal‐to‐noise ratio (PSNR), structural similarity index (SSIM), information entropy (IE), and mean squared error (MSE) as metrics for assessing the transferred images, comparing them with three typical image style transfer methods. Results demonstrate that the proposed method achieves optimal performance across all metrics, realizing superior image style transfer effects.

The component analysis of raw meal is critical to the quality of cement. In recent years, near-infrared (NIR) has been emerged as an innovative and efficient analytical method to determine the oxide content of cement raw meal. This study aims to utilize NIR spectroscopy combined with machine learning and chemometrics to improve the prediction of oxide content in cement raw meal. The Savitzky-Golay convolution smoothing method is applied to eliminate noise interference for the analysis of calcium carbonate (CaCO3), silicon dioxide (SiO2), aluminum oxide (Al2O3), and ferric oxide (Fe2O3) in cement raw materials. Different wavelength selection techniques are used to perform a comprehensive analysis of the model, comparing the performance of several wavelength selection techniques. The back-propagation neural network regression model based on particle swarm optimization algorithm was also applied to optimize the extracted and screened feature wavelengths, and the model prediction performance was checked and evaluated using Rp and RMSE. In conclusion, the results indicate that NIR spectroscopy in combination with ML and chemometrics has great potential to effectively improve the prediction performance of oxide content in raw materials and highlight the importance of modeling and wavelength selection techniques. By enabling more accurate and efficient determination of oxide content in raw materials, NIR spectroscopy coupled with meta-modeling has the potential to revolutionize quality assurance practices in cement manufacturing.