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Abstract Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract Background Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. Methods Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. Results We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. Conclusion COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

Abstract With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

Abstract This article aims to improve the deep-learning-based surface defect recognition. In actual manufacturing processes, there are issues such as data imbalance, insufficient diversity, and poor quality of augmented data in the collected image data for product defect recognition. A novel defect generation method with multiple loss functions, DG2GAN is presented in this paper. This method employs cycle consistency loss to generate defect images from a large number of defect-free images, overcoming the issue of imbalanced original training data. DJS optimized discriminator loss is introduced in the added discriminator to encourage the generation of diverse defect images. Furthermore, to maintain diversity in generated images while improving image quality, a new DG2 adversarial loss is proposed with the aim of generating high-quality and diverse images. The experiments demonstrated that DG2GAN produces defect images of higher quality and greater diversity compared with other advanced generation methods. Using the DG2GAN method to augment defect data in the CrackForest and MVTec datasets, the defect recognition accuracy increased from 86.9 to 94.6%, and the precision improved from 59.8 to 80.2%. The experimental results show that using the proposed defect generation method can obtain sample images with high quality and diversity and employ this method for data augmentation significantly enhances surface defect recognition technology.

Power electronic devices face harsh radiation environments in deep space exploration. It is significant to study the reliability of solder joints of electronic devices in radiation environments. The effect of electron irradiation on the microstructure and mechanical properties of Sn3Ag0.5Cu (SAC305) Ball Grid Array (BGA) solder joints was investigated in this work. The results show that the central position of the SAC305 solder joint surface was damaged after electron irradiation. Then the surface of the solder joints was remelted. The shear strength of solder joints increases as the electron irradiation dose rises. When the electron irradiation dose reaches 80 Mrad, the shear strength of the solder joint is enhanced by 8.62% compared with that of the unirradiated sample. After irradiation, the number of dimples on the fracture surface of solder joints increases and the depth of dimples decreases. Geant4 simulation results show that the surface of solder joint is subject to more severe electron impact than the inside of solder joint is. The interaction between electrons and solder joints is the primary reason for the surface remelting of solder joints.

Abstract Aims Additional evidence has indicated a correlation between N6-methyladenosine (m6A) RNA methylation and cardiovascular disease. Nevertheless, the alterations in RNA methylation modification and the expression of numerous genes remains unclear. This study aimed to identify the role of m6A in ST-segment elevation myocardial infarction (STEMI). Methods Two microarray datasets (GSE123342 and GSE59867) were downloaded from the GEO database. After merging the data and batch normalization, differentially expressed regulators were identified using the limma package. Subtyping consistency analysis was performed to group samples. The random forest algorithm and support vector machine were used to identify diagnostic biomarkers. Immune infiltration and inflammation levels among the subtypes were assessed using a single-sample gene set enrichment analysis. Results A total of 15 key differential m6A regulators (RBM15B, ELAVL1, ALKBH5, METTL16, ZC3H13, RBM15, YTHDC1, YTHDC2, YTHDF3, HNRNPC, FMR1, LRPPRC, HNRNPA2B1, RBMX, FTO) were identified using the random forest classifier and were found to be highly correlated by PPI analysis. Two distinct RNA modification patterns (cluster A and B) were validated based on the expression levels of the 15 key m6A regulators. GO and KEGG annotations showed that immunity and inflammation pathways were enriched. Immune infiltration analysis revealed that cluster 2 had higher immune activation than cluster 1. Further analysis showed that cluster 2 had a higher inflammation level, with IL-4 and IL-33 showing differential expression (p

Abstract Background Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. Results Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. Conclusion It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Our case demonstrated unique cytomegalovirus (CMV) encephalitis post-haploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HID-HSCT. After HSCT, the patient developed CMV viremia and severe acute graft-versus-host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusion-weighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient’s consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes.

Abstract Background Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. Methods Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran’s Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. Results Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003–1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096–2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. Conclusion This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.

Subsurface drip irrigation in arid areas has the potential to replace traditional mulched drip irrigation to achieve green and sustainable cotton production. However, the suitable irrigation amount and frequency are still unclear, which seriously limits the ability of this model to improve water productivity and water-saving potential. Therefore, a field experiment was carried out from 2021 to 2023; a split plot experimental design was adopted with two irrigation amounts (W1, 3177 m3 ha−1; W2, 3840 m3 ha−1) and three irrigation frequencies (F1, 9; F2, 8; F3, 7). The effects of different irrigation strategies on the soil microenvironment, moisture content, biomass, and water use efficiency (WUE) of cotton organs were evaluated. The W2 treatment improved the soil moisture content, increased the soil temperature gradient, and reduced the soil conductivity, thereby increasing the moisture content and biomass of various organs. Moreover, compared with the F1 treatment, the F2 and F3 treatments were more likely to increase the soil moisture content, soil temperature gradient, WUEStem, WUELeaf and WUEBoll. In addition, the water consumption of the F2 and F3 treatments decreased by 3.9 % and 0.9 %, respectively, compared with that of the F1 treatment. These findings indicate that W2F2 can reduce water consumption while increasing boll biomass and WUEBoll. Further analysis revealed that under W2F2, WUEBoll was positively correlated with soil temperature gradient and soil conductivity and negatively correlated with leaf moisture content (LMC) and water consumption. In summary, with an irrigation amount of 3840 m3 ha−1, delaying the initial irrigation event and increasing the irrigation quota (8 irrigation events) improve the water environment in cotton fields, reducing soil temperature fluctuations and surface salt accumulation and synergistically increasing the boll biomass of cotton organs and WUEBoll. This irrigation strategy represents an effective cotton cultivation method to maximize cotton yield and improve resource utilization efficiency.

Bacteria-mediated antitumor therapy has gained widespread attention for its innate tumor-targeting capability and excellent immune activation properties. Nevertheless, the clinical approval of bacterial therapies remains elusive primarily due to the formidable challenge of balancing safety with enhancing in vivo efficacy. In this study, leveraging the probiotic Escherichia coli Nissle1917 (EcN) emerges as a promising approach for colon cancer therapy, offering a high level of safety attributed to its lack of virulence factors and its tumor-targeting potential owing to its obligate anaerobic nature. Specifically, we delineate the erythrocyte (RBC) membrane-camouflaged EcN, termed as Trojan horse EcN@RBC, which triggers apoptosis in tumor cells by mitigating mitochondrial membrane potential (MMP) and subsequently activating the PINK1/Parkin pathway associated with mitophagy. Concurrently, the decline in MMP induced by mitophagy disrupts the mitochondrial permeability transition pore (MPTP), leading to the release of Cytochrome C and subsequent apoptosis induction. Moreover, synergistic effects were observed through the combination of the autophagy activator rapamycin, bolstering the antitumor efficacy in vivo. These findings offer novel insights into probiotic-mediated antitumor mechanisms and underscore the therapeutic potential of EcN@RBC for colon cancer patients.

Hepatitis B virus (HBV)-related liver disease poses a major threat to human health worldwide. Although interferon and nucleoside analogues are commonly administered for treating chronic HBV infection, their use is limited by considerable side effects, drug resistance and incapacity for HBV elimination. Hence, novel HBV therapeutics are urgently required. For numerous years, traditional Chinese botanical drugs have been widely used to treat HBV-related diseases. The natural metabolites derived from these traditional drugs exhibit significant anti-HBV effects and serve as potential novel drugs for treating HBV. For overall understanding the therapeutic potential of these metabolites, the anti-HBV effects and mechanisms of action of 107 natural metabolites are summarized in this article. Mechanistically, these natural metabolites exert their anti-HBV effects by influencing the expression and function of host and/or viral genes, which differs from the mechanism of action of nucleoside analogues. Indeed, combining natural metabolites with nucleoside analogues can exert synergistic effects. Accordingly, natural metabolites or their chemically modified derivatives represent potential novel drugs and adjuvants for anti-HBV treatment.

Variety detection provides technical support for selecting XinHui citrus for use in the production of XinHui dried tangerine peel. Simultaneously, the mutual occlusion between tree leaves and fruits is one of the challenges in object detection. In order to improve screening efficiency, this paper introduces a YOLO(You Only Look Once)v7-BiGS(BiFormer&GSConv) citrus variety detection method capable of identifying different citrus varieties efficiently. In the YOLOv7-BiGS network model, initially, the BiFormer attention mechanism in the backbone of the YOLOv7-based network strengthens the model’s ability to extract citrus’ features. In addition, the introduction of the lightweight GSConv convolution in place of the original convolution within the ELAN of the head component effectively streamlines model complexity while maintaining performance integrity. To environment challenge validate the effectiveness of the method, the proposed YOLOv7-BiGS was compared with YOLOv5, YOLOv7, and YOLOv8. In the comparison of YOLOv7-BiGS with YOLOv5, YOLOv7, and YOLOv8, the experimental results show that the precision, mAP and recell of YOLOv7-BiGS are 91%, 93.7% and 87.3% respectively. Notably, compared to baseline methods, the proposed approach exhibited significant enhancements in precision, mAP, and recall by 5.8%, 4.8%, and 5.2%, respectively. To evaluate the efficacy of the YOLOv7-BiGS in addressing challenges posed by complex environmental conditions, we collected occluded images of Xinhui citrus fruits from the Xinhui orchard base for model detection. This research aims to fulfill performance criteria for citrus variety identification, offering vital technical backing for variety detection endeavors.

Background Sepsis, an infection-triggered inflammatory syndrome, poses a global clinical challenge with limited therapeutic options. Our study is designed to identify potential diagnostic biomarkers of sepsis onset in critically ill patients by bioinformatics analysis. Methods Gene expression profiles of GSE28750 and GSE74224 were obtained from the Gene Expression Omnibus (GEO) database. These datasets were merged, normalized and de-batched. Weighted gene co-expression network analysis (WGCNA) was performed and the gene modules most associated with sepsis were identified as key modules. Functional enrichment analysis of the key module genes was then conducted. Moreover, differentially expressed gene (DEG) analysis was conducted by the “limma” R package. Protein-protein interaction (PPI) network was created using STRING and Cytoscape, and PPI hub genes were identified with the cytoHubba plugin. The PPI hub genes overlapping with the genes in key modules of WGCNA were determined to be the sepsis-related key genes. Subsequently, the key overlapping genes were validated in an external independent dataset and sepsis patients recruited in our hospital. In addition, CIBERSORT analysis evaluated immune cell infiltration and its correlation with key genes. Results By WGCNA, the greenyellow module showed the highest positive correlation with sepsis (0.7, p = 2e − 19). 293 DEGs were identified in the merged datasets. The PPI network was created, and the CytoHubba was used to calculate the top 20 genes based on four algorithms (Degree, EPC, MCC, and MNC). Ultimately, LTF, LCN2, ELANE, MPO and CEACAM8 were identified as key overlapping genes as they appeared in the PPI hub genes and the key module genes of WGCNA. These sepsis-related key genes were validated in an independent external dataset (GSE131761) and sepsis patients recruited in our hospital. Additionally, the immune infiltration profiles differed significantly between sepsis and non-sepsis critical illness groups. Correlations between immune cells and these five key genes were assessed, revealing that plasma cells, macrophages M0, monocytes, T cells regulatory, eosinophils and NK cells resting were simultaneously and significantly associated with more than two key genes. Conclusion This study suggests a critical role of LTF, LCN2, ELANE, MPO and CEACAM8 in sepsis and may provide potential diagnostic biomarkers and therapeutic targets for the treatment of sepsis.

Abstract Background Several biallelic truncating and missense variants of the gem nuclear organelle–associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early‐infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. Purpose This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub‐regional locations. Methods We performed whole‐exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype–phenotype relationship. Results Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147‐154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603‐154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression‐bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR‐like domain or RBS domain were more likely to be associated with epilepsy. Conclusions We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

Abstract Electroencephalogram (EEG) is one of the most important bioelectrical signals related to brain activity and plays a crucial role in clinical medicine. Driven by continuously expanding applications, the development of EEG materials and technology has attracted considerable attention. However, systematic analysis of the sustainable development of EEG materials and technology is still lacking. This review discusses the sustainable development of EEG materials and technology. First, the developing course of EEG is introduced to reveal its significance, particularly in clinical medicine. Then, the sustainability of the EEG materials and technology is discussed from two main aspects: integrated systems and EEG electrodes. For integrated systems, sustainability has been focused on the developing trend toward mobile EEG systems and big‐data monitoring/analyzing of EEG signals. Sustainability is related to miniaturized, wireless, portable, and wearable systems that are integrated with big‐data modeling techniques. For EEG electrodes and materials, sustainability has been comprehensively analyzed from three perspectives: performance of different material/structural categories, sustainable materials for EEG electrodes, and sustainable manufacturing technologies. In addition, sustainable applications of EEG have been presented. Finally, the sustainable development of EEG materials and technology in recent decades is summarized, revealing future possible research directions as well as urgent challenges.

Abstract Background Alzheimer’s disease (AD) represents profound degenerative conditions of the brain that cause significant deterioration in memory and cognitive function. Despite extensive research on the significant contribution of lipid metabolism to AD progression, the precise mechanisms remain incompletely understood. Hence, this study aimed to identify key differentially expressed lipid metabolism-related genes (DELMRGs) in AD progression. Methods Comprehensive analyses were performed to determine key DELMRGs in AD compared to controls in GSE122063 dataset from Gene Expression Omnibus. Additionally, the ssGSEA algorithm was utilized for estimating immune cell levels. Subsequently, correlations between key DELMRGs and each immune cell were calculated specifically in AD samples. The key DELMRGs expression levels were validated via two external datasets. Furthermore, gene set enrichment analysis (GSEA) was utilized for deriving associated pathways of key DELMRGs. Additionally, miRNA-TF regulatory networks of the key DELMRGs were constructed using the miRDB, NetworkAnalyst 3.0, and Cytoscape software. Finally, based on key DELMRGs, AD samples were further segmented into two subclusters via consensus clustering, and immune cell patterns and pathway differences between the two subclusters were examined. Results Seventy up-regulated and 100 down-regulated DELMRGs were identified. Subsequently, three key DELMRGs (DLD, PLPP2, and PLAAT4) were determined utilizing three algorithms [(i) LASSO, (ii) SVM-RFE, and (iii) random forest]. Specifically, PLPP2 and PLAAT4 were up-regulated, while DLD exhibited downregulation in AD cerebral cortex tissue. This was validated in two separate external datasets (GSE132903 and GSE33000). The AD group exhibited significantly altered immune cell composition compared to controls. In addition, GSEA identified various pathways commonly associated with three key DELMRGs. Moreover, the regulatory network of miRNA-TF for key DELMRGs was established. Finally, significant differences in immune cell levels and several pathways were identified between the two subclusters. Conclusion This study identified DLD, PLPP2, and PLAAT4 as key DELMRGs in AD progression, providing novel insights for AD prevention/treatment.

Abstract MoS2 has attracted intense interest in many applications. Natural MoS2 and field-effect transistors made of it generally exhibit n-type characteristics, but its origin is unknown. Herein, we show that C is the origin of the universal n-type doping of natural MoS2. Photoemission spectroscopies reveal that while many MoS2 samples with C detected are n-type, some without C exhibit p-type characteristics. The C-free, p-type MoS2 changes to n-type over time with the concurrent appearance of C that is out-diffused from bulk, indicating that C induces the n-type doping. The C-origin is verified by C-deposition and supported by theoretical calculations. This carbon appears as nanometer-scale defects frequently observed in scanning tunneling microscopy. In addition, we propose, based on the calculations, that S vacancies are responsible for the p-type characteristics, which contrasts with the widespread belief. This work provides new perspectives on MoS2 doping and presents a new direction for fabricating reliable MoS2 devices.

Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. The Ganoderma lucidum polysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy.

Seed size traits, including seed length (SL), seed width (SW), and seed thickness (ST), are crucial appearance parameters that determine soybean seed weight, yield, and ultimate utilization. However, there is still a large gap in the understanding of the genetic mechanism of these traits. Here, 281 soybeans were utilized to analyze the genetic architecture of seed size traits in different years through multiple (single-locus and multi-locus) genome-wide association study (GWAS) models, and candidate genes were predicted by integrating information on gene function and transcriptome sequencing data. As a result, two, seven, and three stable quantitative trait nucleotides (QTNs) controlling SL, SW, and ST were detected in multiple environments using the single-locus GWAS model, and concurrently detected by the results of the multi-locus GWAS models. These stable QTNs are located on 10 linkage disequilibrium blocks, with single genome regions ranging in size from 20 to 440 kb, and can serve as the major loci controlling soybean seed size. Furthermore, by combining gene functional annotation and transcriptome sequencing data of seeds at different developmental stages from two extreme soybean accessions, nine candidate genes, including Glyma.05G038000, Glyma.05G244100, Glyma.05G246900, Glyma.07G070200, Glyma.11G010000, Glyma.11G012400, Glyma.17G165500, Glyma.17G166500, and Glyma.20G012600 within the major loci that may regulate soybean seed size, were mined. Overall, these findings offer valuable insights for molecular improvement breeding as well as gene functional studies to unravel the mechanism of soybean seed size.

The structural design of steel–titanium composite plates significantly affects their corrosion resistance. To investigate the impact of defects of different shapes and sizes on the corrosion behavior of steel–titanium composite plates, this study designed six types of defects and conducted a series of characterization tests. The results showed that due to the galvanic interaction between carbon steel and titanium alloy, small defects initially accelerate corrosion, resulting in 50% to 200% more corrosion weight loss compared to large defects. However, in the later stages of immersion, the corrosion rate of small defects decreased by up to 35%, which was attributed to the accumulation of protective corrosion products. Additionally, there is an inverse relationship between the corrosion rate and the thickness ratio of the composite plate. The reduction in the area of Q345B also results in additional corrosion loss of up to 32%.

Cotton (Gossypium hirsutum L.) production efficiency is constrained by issues such as a low nitrogen (N) utilization rate (30–35 %) and high N application rate (300–350 kg ha−1) in particular arid climates, such as Xinjiang, the largest irrigated cotton-producing region in China. These issues could be alleviated by allocating more N to late application to satisfy plant needs for growth and development. Over a three-year (2019–2021) field experiment, 240 kg ha−1 N was applied in 3 periods (squaring, flowering to peak boll, and late peak boll). The amount of N applied in the second period was fixed at 60 %, and the remaining 40 % was split between the first and the third periods, with five ratios (treatments), i.e., 0:6:4 (N064), 1:6:3 (N163), 2:6:2 (N262), 3:6:1 (N361) and 4:6:0 (N460), to investigate cotton response in terms of growth, biomass accumulation, and yield. Compared with the conventional treatment (N262), the N064 treatment narrowed the plant width by 11.7–12.0 %, increased canopy light transmittance by 6.1–56.9 %, extended the boll growth period by 8.8–9.4 %, improved defoliation by 9.3–11.7 % and increased both seed cotton yield and N partial factor productivity by 7.1–8.1 %, depending on the year. N064 accumulated 4.3–39.5 % more biomass (K) than N262, with the average and maximum growth rates of the reproductive organs (Vt and Vm, respectively) increasing by 8.6–89.0 % and 6.9–125.7 %, respectively, while the fast growth duration (∆t) shortened by 9.9–31.6 %. Again, N064 partitioned 1.5–35.8 % more biomass to bolls (higher partitioning index, PIboll). Seed cotton yield was significantly positively correlated with K, t1, Vt, Vm and PIboll and negatively correlated with ∆t in reproductive organs. Collectively, the data suggest that allocating more N to late application could be an efficient N fertilizer management strategy in arid areas under N-reduced cultivation and fertigation.

The pod and seed counts are important yield-related traits in soybean. High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner. Recent advances in artificial intelligence, especially deep learning (DL) models, have provided new avenues for high-throughput phenotyping of crop traits with increased precision. However, the available DL models are less effective for phenotyping pods that are densely packed and overlap in in situ soybean plants; thus, accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge. To address this challenge, the present study proposed a bottom-up model, DEKR-SPrior (disentangled keypoint regression with structural prior), for in situ soybean pod phenotyping, which considers soybean pods and seeds analogous to human people and joints, respectively. In particular, we designed a novel structural prior (SPrior) module that utilizes cosine similarity to improve feature discrimination, which is important for differentiating closely located seeds from highly similar seeds. To further enhance the accuracy of pod location, we cropped full-sized images into smaller and high-resolution subimages for analysis. The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models, viz., Lightweight-OpenPose, OpenPose, HigherHRNet, and DEKR, reducing the mean absolute error from 25.81 (in the original DEKR) to 21.11 (in the DEKR-SPrior) in pod phenotyping. This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping, and we hope that DEKR-SPrior will help future plant phenotyping.

Xinhui tangerine peel has valuable medicinal value. The longer it is stored in an appropriate environment, the higher its flavonoid content, resulting in increased medicinal value. In order to correctly identify the age of the tangerine peel, previous studies have mostly used manual identification or physical and chemical analysis, which is a tedious and costly process. This work investigates the automatic age recognition of the tangerine peel based on deep learning and attention mechanisms. We proposed an effective ConvNeXt fusion attention module (CNFA), which consists of three parts, a ConvNeXt block for extracting low-level features’ information and aggregating hierarchical features, a channel squeeze-and-excitation (cSE) block and a spatial squeeze-and-excitation (sSE) block for generating sufficient high-level feature information from both channel and spatial dimensions. To analyze the features of tangerine peel in different ages and evaluate the performance of CNFA module, we conducted comparative experiments using the CNFA-integrated network on the Xinhui tangerine peel dataset. The proposed algorithm is compared with related models of the proposed structure and other attention mechanisms. The experimental results showed that the proposed algorithm had an accuracy of 97.17%, precision of 96.18%, recall of 96.09%, and F1 score of 96.13% for age recognition of the tangerine peel, providing a visual solution for the intelligent development of the tangerine peel industry.

High primary rock stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different rock breaking states under different primary rock stress conditions. There are a large number of naturally formed joints in rock mass, due to the limitations of laboratory tests, a numerical model of jointed rock mass was established using LS-DYNA software to investigate the evolution of blasting damage under various in-situ stresses and open joints. In this simulation, using the Lagrange-Euler (ALE) procedure and the equation of state (JWL) that defines explosive materials, the study considered different joint thicknesses (2cm, 4cm, and 6cm), joint angles (0°, 30°, 60°, and 90°), and in-situ stress conditions (lateral stress coefficients of 0.5, 1, and 2, with vertical in-situ stresses of 10MPa and 20MPa), through stress analysis and damage area comparison, the relationship between damage crack propagation and horizontal and vertical stress difference is explored. The research aimed to understand the mechanisms underlying crack initiation and propagation. The results show that: (1) The presence of joints exerts a barrier effect on the expansion and penetration of cracks. When explosion stress waves reach the joint surface, their propagation is impeded, leading to the diffusion of wing cracks at the joint ends. When the lateral stress coefficient and joint angle are the same, an increase in initial in-situ stress results in a reduction in the area of the blasting damage zone. (2) Under the same initial in-situ stress conditions, the area of the blasting damage zone initially increases and then decreases with an increasing joint angle. However, it remains larger than that without a joint, and there exists an optimal angle that maximizes the damage area. In the simulated conditions, the area of damage cracks is greatest when the joint angle is 60° dip angle. (3) The presence of initial in-situ stress has a certain impact on the initiation and expansion of blasting cracks. The degree and nature of this influence are not solely related to the lateral stress coefficient but also depend on the joint's angle and thickness. When in-situ stress is present, the initial in-situ stress field's pressure is not conducive to the initiation and propagation of blasting cracks. However, the existence of a joint has a noticeable guiding and promoting effect on crack propagation, and the pattern of crack propagation is influenced by both joint and in-situ stress conditions.

As an enduring Chinese freshwater aquaculture product, the Eriocheir sinensis has a high economic value and is characterized by a catadromous life style that undergoes seawater–freshwater migration. However, little is known about their gut microbial status as they move from saltwater to freshwater acclimatization. Here, we sampled and cultivated Eriocheir sinensis megalopa from three aquaculture desalination ponds and investigated their gut microbiota diversity, community structures and biotic interactions from megalopa stage to the first juvenile stage after desalination for 9 days. Our results revealed that during the transition from megalopa to the first juvenile in Eriocheir sinensis, a significant change in gut microbial composition was observed (for instance, changes in relative abundance of dominant phyla), which was, however, not influenced by different sampling sites. The species diversity (such as the richness) of the gut microbiota showed a hump-shaped pattern along the succession. However, the compositional differences of the gut microbes showed constantly increasing patterns during the succession after freshwater adaption for all three sampling sites. Further co-occurrence analysis also showed that the complexity of the ecological networks in gut microbes was significantly enhanced during the development, such as increasing numbers of network links, connectivity and modularity, and was confirmed by decreasing average path length and proportions of negative links. Taken together, the differences in community structures and biological interactions of gut microorganisms were more pronounced in Eriocheir sinensis megalopa during desalination than in diversity and species compositions. This implies that the gut microbes of Eriocheir sinensis megalopa would become more robust and adaptive during the developmental process.

Phosphorus (P) stands as a pivotal macroelement in relation to the growth of plants. It plays a significant role in physiological processes, as components of biofilms and nucleotides, and in metabolic activities within plants. The deprivation of phosphorus detrimentally impacts the growth and developmental of plants. However, the rhizosphere’s beneficial fungi and bacteria augment the efficacy of phosphorus uptake, participate in the molecular regulation of phosphorus, stimulate physiological alterations in plants, and facilitate signal transmission. In order to give readers a better understanding of the effects and positive roles of soil beneficial fungi and bacteria in regulating plant phosphorus acquisition and transport, this present review introduces the role and influence of rhizosphere microorganisms (fungi and bacteria) in assisting plant phosphorus absorption, and summarizes the key phosphorus transporters found in their interaction with plants. Using mixed microbial populations as composite microbial fertilizers has a positive effect on plants under phosphorus-deficiency conditions. It will be conducive to a better understanding of the mutualistic relationship between fungi, bacteria, and plants to provide a way to reduce the application of phosphorus fertilizers efficiently, and to provide a research background for the development of microbiological fertilizers.

In this article, we report the pathogenicity of a new strain of fungus, Rhizopus oryzae to honeybee larvae, isolated from the chalkbrood-diseased mummies of honeybee larvae and pupae collected from apiaries in China. Based on morphological observation and internal transcribed spacer (ITS) region analyses, the isolated pathogenic fungus was identified as R. oryzae. Koch’s postulates were performed to determine the cause-and-effect pathogenicity of this isolate fungus. The in vitro pathogenicity of this virulent fungus in honeybees was tested by artificially inoculating worker larvae in the lab. The pathogenicity of this new fungus for honeybee larvae was both conidial-concentration and exposure-time dependent; its highly infectious and virulent effect against the larvae was observed at 1 × 105 conidia/larva in vitro after 96 h of challenge. Using probit regression analysis, the LT50 value against the larvae was 26.8 h at a conidial concentration of 1 × 105 conidia/larva, and the LC50 was 6.2 × 103 conidia/larva. These results indicate that the new isolate of R. oryzae has considerable pathogenicity in honeybee larvae. Additionally, this report suggests that pathogenic phytofungi may harm their associated pollinators. We recommend further research to quantify the levels, mechanisms, and pathways of the pathogenicity of this novel isolated pathogen for honeybee larvae at the colony level.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new “valve-off” starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced “valve-off” strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.

Cancer represents a challenging medical problem worldwide. Several exploratory studies have been conducted to overcome these limitations. RNA vaccines play an important role in cancer prevention and treatment. Recent studies have shown that RNA vaccines play an important role in cancer prevention. However, there are currently no relevant bibliometric studies. This study aimed to apply bibliometrics to summarize the knowledge structure and research hotspots regarding the role of RNA vaccines in cancer. Publications related to RNA vaccines in cancer were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis. A total of 1399 articles were included, comprising 803 original articles and 596 reviews. The number of studies on RNA vaccines against cancer has been increasing annually. China and the United States were the principal countries of origin of publications. Johannes Gutenberg University Mainz, NCI, and Duke University were the main organizations. Frontiers in Immunology is the leading journal in the field. Hot keywords included tumor antigens, lipid nanoparticles, emerging roles, and dendritic cells. This is the bibliometric study to summarize the research trends and development of RNA vaccines for cancer. This information will provide a reference for researchers studying RNA vaccines against cancer.

IntroductionLow agricultural nutrient input efficiency remains a significant impediment for crop production globally. To address this issue in cotton agroecosystems, there is a need to develop sustainable crop nutrient management strategies to achieve high crop yields. We hypothesized that organic liquid fertilizer (OF) combined with reduced chemical fertilizer (CF) would enhance cotton yield by improving leaf functioning and soil properties. However, the underlying mechanism and its related process is poorly understood.MethodsThis study explored the effects of OF combined with reduced CF on cotton yield, physiology and soil properties. Treatments included a single application of CF (CF: N, P2O5 and K2O applied at 228, 131 and 95 kg ha−1) and combined applications of OF and CF (OF0.6−OF1.4) in the following ratios: OF0.6, OF+60% CF; OF0.8, OF+80% CF; OF1.0, OF+100% CF; OF1.2, OF+120% CF; OF1.4, OF+140% CF. Results and discussionThe result showed that compared with CF, OF0.8, OF1.0 and OF1.2 increased soil organic matter (SOM) content by 9.9%, 16.3% and 23.7%, respectively. Compared with CF, the OF0.6, OF0.8, OF1.0, and OF1.2 treatments increased leaf area (LA) by 10.6−26.1%, chlorophyll content (Chl content) by 6.8−39.6%, and the efficiency of photosystem II (PSII) light energy (Y(II)), electron transfer rate of PSII (ETR) and photochemical quenching (qP) by 3.6−26.3%, 4.7−15.3% and 4.3−9.8%, respectively. The OF0.8 treatment increased net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (E) by 22.0%, 27.4% and 26.8%, respectively, resulting in higher seed cotton yield. The seed cotton yield and economic coefficient were positively correlated with Pn, E, Gs and Y(II) from the full boll stage to the boll opening stage. In summary, the OF0.8 treatment can maintain a high SOM content and photosynthetic performance with reduced chemical fertilizer input without sacrificing yield. The integration of OF+80% CF (OF0.8) is a promising nutrient management strategy for highly efficient cotton production under mulch drip irrigation systems.

IntroductionEntomopathogenic fungi (EPF) can colonize and establish symbiotic relationships with plants as endophytes. Recently, EPF have been reported to suppress plant pathogens and induce plant resistance to diseases. However, the potential mechanisms via which EPF as endophytes control major plant diseases in situ remain largely unknown.MethodsPot and field experiments were conducted to investigate the mechanisms via which an EPF, Beauveria bassiana, colonizes tomato, under Botrytis cinerea infection stress. B. bassiana blastospores were inoculated into tomato plants by root irrigation. Tomato resistance to tomato gray mold caused by B. cinerea was evaluated by artificial inoculation, and B. bassiana colonization in plants and rhizosphere soil under B. cinerea infection stress was evaluated by colony counting and quantitative PCR. Furthermore, the expression levels of three disease resistance-related genes (OXO, CHI, and atpA) in tomato leaves were determined to explore the effect of B. bassiana colonization on plant disease resistance performance in pot experiments.ResultsB. bassiana colonization could improve resistance of tomato plants to gray mold caused by B. cinerea. The incidence rate, lesion diameter, and disease index of gray mold decreased in both the pot and field experiments following B. bassiana colonization. B. bassiana was more likely to accumulate in the pathogen infected leaves, while decreasing in the rhizosphere soil, and induced the expression of plant resistance genes, which were up-regulated in leaves.DiscussionThe results indicated that plants could “recruit” B. bassiana from rhizosphere soil to diseased plants as directional effects, which then enhanced plant growth and resistance against pathogens, consequently inhibiting pathogen infection and multiplication in plants. Our findings provide novel insights that enhance our understanding of the roles of EPF during pathogen challenge.

Background: Tripterygium glycosides have been used to treat systemic lupus erythematosus (SLE) for a long time, showing the effects of immune regulation. We aimed to evaluate the benefits and risks of Tripterygium Glycosides Tablets (TGT) for patients with SLE.Methods: We searched electronic databases and clinical trial registries for relevant randomized controlled trials (RCTs). We identified eligible RCTs and assessed risk of bias. We conducted a meta-analysis to estimate the pooled effects. The Trial Sequential Analysis (TSA) 0.9.5.10 software was used to verify the reliability of the results.Results: Eight RCTs encompassing 538 patients with SLE were included. TGT combined with conventional treatments (CTs) was superior to CTs alone in reducing lupus activity (MD = −1.66, 95% CI = −2.07 to −1.26, p < 0.00001, low-certainty evidence) and improving overall response rate (ORR) (RR = 1.21, 95% CI = 1.11 to 1.32, p < 0.0001, moderate-certainty evidence). The robustness of the results was confirmed by TSA. Regarding safety, there was no statistical difference in the overall incidence of adverse reactions between the two groups.Conclusion: In patients with SLE, TGT might safely reduce disease activity. However, further high-quality studies are needed to firmly establish the clinical efficacy of TGT.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022300474; Identifier: CRD42022300474.

Gene flow is crucial for maintaining population genetic diversity and increasing the adaptive potential of species. Therefore, identifying factors affecting gene flow is important for conservation planning, especially for threatened mammals in complex mountain system. In this study, we conducted a microgeographic-scale landscape genetic analysis for the endangered and ecologically isolated Alashan red deer (Cervus elaphus alxaicus) for the first time. Using data from 329 individuals for 11 microsatellite loci, we assessed how the environmental factors in the Chinese Helan Mountains affect the gene flow of this species. Three genetic clusters were identified by both Bayesian (STRUCTURE and GENELAND) and non-Bayesian (DAPC) methods, revealing clear spatial genetic structure within a limited geographic range. Landscape genetic analysis based on causal modelling and linear mixed-effect modelling revealed that gene flow was primarily restricted by topographic factors, including topographic complexity, aspect, altitude and slope, rather than geographical distance or anthropogenic barriers. Based on these results, we identified two important corridors that can potentially facilitate gene flow within the complex landscape of the Helan Mountains. Our results highlight the role of natural landscape features on Alashan red deer's population genetic structure and functional connectivity. This differs from findings regarding red deer populations in other regions, indicating that landscape genetic patterns are not homogenous across the range of a species, but rather differ among specific landscapes.

Abstract Background The economic and environmental value of honeybees has been severely challenged in recent years by the collapse of their colonies worldwide, often caused by outbreaks of infectious diseases. However, our understanding of the diversity, prevalence, and transmission of honeybee viruses is largely obscure due to a lack of large-scale and longitudinal genomic surveillance on a global scale. Results We report the meta-transcriptomic sequencing of nearly 2000 samples of the two most important economic and widely maintained honeybee species, as well as an associated ectoparasite mite, collected across China during 2016–2019. We document the natural diversity and evolution of honeybee viruses in China, providing evidence that multiple viruses commonly co-circulate within individual bee colonies. We also expanded the genomic data for 12 important honeybee viruses and revealed novel genetic variants and lineages associated with China. We identified more than 23 novel viruses from the honeybee and mite viromes, with some exhibiting ongoing replication in their respective hosts. Together, these data provide additional support to the idea that mites are an important reservoir and spill-over host for honeybee viruses. Conclusions Our data show that honeybee viruses are more widespread, prevalent, and genetically diverse than previously realized. The information provided is important in mitigating viral infectious diseases in honeybees, in turn helping to maintain sustainable productive agriculture on a global scale. Video Abstract

Abstract Background Chlorophyll is a very important pigment involved in photosynthesis, while plant acyl-CoA biosynthesis is derived from plastid-localized fatty acids (FAs). Until now, the regulation of the acyl-CoA pathway for chlorophyll biosynthesis is still unknown. Results Here, we identified a long-chain acyl-CoA synthetase (LACS) gene BnLACS9 from Brassica napus. BnLACS9 complemented a LACS-deficient yeast strain YB525, which indicated that BnLACS9 has the LACS function. BnLACS9 was localized in the chloroplast envelope membrane, while mainly expressed in young leaves and flowers. Overexpression of BnLACS9 in Nicotiana benthamiana resulted in an increase in total CoA and MGDG content. In B. napus with overexpression of BnLACS9, the number of chloroplast grana lamellae and the chlorophyll content, as well as the MGDG and DGDG contents, increased compared to wild type. The net photosynthetic rate, dry weight of the entire plant and oil content of seeds increased significantly, accompanied by an increase in chlorophyll content. Transcriptome analysis revealed that overexpression of BnLACS9 improved the pathway of acyl-CoA biosynthesis and further improved the enzymes in the glycolipid synthesis pathway, while acyl-CoA was the substrate for glycolipid synthesis. The increased glycolipids, especially MGDG and DGDG, accelerated the formation of the chloroplast grana lamellae, which increased the number of chloroplast thylakoid grana lamella and further lead to increased chlorophyll content. Conclusions In the present study, we demonstrated that BnLACS9 played a crucial role in glycolipids and chlorophyll biosynthesis in B. napus. The results also provide a new direction and theoretical basis for the improvement of the agronomic traits of plants.

Background & aims: Sarcopenia is an age-related disease that increases the risk of falls and fractures in older adults. However, there is no blood biochemical marker to help to predict or diagnose sarcopenia in clinical practice. Soluble interleukin 2 receptor (sIL-2R) was reported to be associated with muscle satellite cell dysfunction which played an important role in the pathogenesis of sarcopenia. Thereby, we aimed to explore the association between serum sIL-2R and sarcopenia in older adults at high risk of fractures. Methods: A total of 429 hospitalized older adults (age ≥55 years) were enrolled in this cross-sectional study (mean age ​= ​66.62 ​± ​6.59 years; 62.7% female). Logistic regression analysis was performed to assess the association of sIL-2R with sarcopenia, muscle mass, muscle strength, and physical performance, respectively. The optimal models for the diagnosis of sarcopenia and low hand grip strength (HGS) were established by multivariable binary logistic regression analysis with backward selection, and further were evaluated for the diagnostic values by receiver operating characteristic (ROC) curve. Results: Higher sIL-2R levels were found in sarcopenia than no-sarcopenia group in male (median 421 U/mL (interquartile range [IQR] 217 U/mL) vs median 362 U/mL (IQR 157 U/mL); n ​= ​77 vs 83; p ​

Chemical topping with 1,1-dimethylpiperidinium chloride (DPC) has been considered a promising measure to inhibit apical dominance in cotton (Gossypium hirsutum L.). However, knowledge of the plant growth and canopy development of cotton under chemical topping with DPC remains limited, and the effect of this practice on lint yield and defoliation is unclear. A two-year (2019–2020) field experiment was conducted with two varieties, Xinluzao 60 (L60, DPC-insensitive) and Jinken1402 (JK1402, DPC-sensitive), and four topping methods, manual topping (MT), no topping (NT), DPC+ (fortified DPC) and DPC. We found that the lint yields of L60 and JK1402 treated with DPC were equivalent to those of L60 and JK1402 treated with DPC+ but were enhanced by 0.9–4.7% in L60 and 6.7–11.8% in JK1402 relative to those under MT and NT, with no significant difference in fiber quality. This was mainly due to the change in plant growth and canopy structure. In particular, compared with MT, application of DPC shortened the upper branches and extended the duration of the leaf area index peak. Moreover, in the late reproductive period, DPC application increased the number of upper leaves and reduced diffuse noninterceptance. Notably, the light transmittance rate (LLR) of JK1402 treated with DPC was higher than that of MT in the middle and lower parts of the canopy. Furthermore, there was positive correlation between LLR and defoliation rate. Therefore, chemical topping with DPC provided an effective alternative for manual topping.

Abstract Rockbursts are some of the most severe dynamic disasters in coal mines. In this paper, the discrimination method of the tectonic stress field is proposed by analyzing the modern stress field in China. The tectonic stress field formed by modern tectonic movement guides in situ stress measurements. According to the stress state classification, most rockbursts in coal mines in China are closely associated with tectonic stress. For tectonic stress-driven rockbursts, modern tectonic movement and modern tectonic stress fields must be considered. The stress change and energy transfer caused by tectonic movement affect the geological structure where coal mines are located. Energy accumulation under rockburst conditions is mainly formed by natural geo-dynamic movement and the mining configuration, and energy accumulation is the basis for rockbursts. The application of the geo-dynamic environmental evaluation method to determine the coalfield geo-dynamic process and the influence of modern tectonic movement is proposed. Accordingly, the classification method of rockbursts in coal mines is established. Based on the distribution characteristics of modern tectonic conditions in China, it is revealed that these dynamic disasters follow a “110” distribution. Finally, a “three condition” criteria of rockbursts is proposed: the geo-dynamic environment is a necessary condition for rockbursts, mining disturbance is a sufficient condition for rockbursts, and risk-releasing measures are a condition controlling rockburst risk mitigation.

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease.

Background: Whole-genome bisulfite sequencing (WGBS) technology can provide comprehensive DNA methylation at a single-base resolution on a genome-wide scale, and is considered to be the gold standard for the detection of 5-methylcytosine (5 mC). However, the International Human Epigenome Consortium propose a full DNA methylome should have at least 30 fold redundant coverage of the reference genome from a single biological replicate. Therefore, it remains cost prohibitive for large-scale studies. To find a solution, the DNBSEQ-Tx sequencing was developed that can generate up to 6 Tb data in a single run for projects involving large-scale sequencing. Results: In this study, we provided two WGBS library construction methods DNB_PREBSseq and DNB_SPLATseq optimized for the DNBSEQ-Tx sequencer, and demonstrated the performance of these two methods on the DNBSEQ-Tx platform, using the DNA extracted from four different cell lines. We also compared the sequencing data from these two WGBS library construction methods with HeLa cell line data from ENCODE sequenced on Illumina HiSeq X Ten and WGBS data of two other cell lines sequenced on HiSeq2500. Various quality control (QC) analyses such as the base quality scores, methylation-bias (m-bias), and conversion efficiency indicated that the data sequenced on the DNBSEQ-Tx platform met the WGBS-required quality controls. Meanwhile, our data closely resembled the coverage shown by the data generated by the Illumina platform. Conclusions: Our study showed that with our optimized methods, DNBSEQ-Tx could generate high-quality WGBS data with relatively good stability for large-scale WGBS sequencing applications. Thus, we conclude that DNBSEQ-Tx can be used for a wide range of WGBS research.

Oil crops are the second most cultivated economic crop in the world after food crops, and they are an important source of both edible and industrial oil. The growth of oil crops is limited by biotic and abiotic stresses, which hinder their yield and quality. Among all the agronomic measures, plant growth promoting bacteria (PGPB) play a crucial role in improving the yield, quality, and adaptability of oil crops. In this review, we considered the recent research on the sources of beneficial bacteria and their interactions with and influences on host plants, with a focus on summarizing the important roles and molecular mechanisms of PGPB in promoting growth and resisting biotic and abiotic stresses in oil crops. Finally, we outlined the current opportunities and challenges of microbial strategies for the improvement of the yield, quality, and adaptability of oil crops, providing a theoretical basis for the future use of microbial inoculants in these crops.

Abstract Objective Mechanical damage plays an essential role in the progression of atherosclerosis. Piezo1 is a new mechanically sensitive ion channel. The present study investigated the vascular smooth muscle cells (VSMCs) apoptosis induced by Piezo1 activation and explored its underlying mechanism. Methods We evaluated cell viability and apoptosis rate with cell counting kit-8 (CCK-8) and Annexin V-FITC/PI flow cytometry assay, respectively. And then Western blot was performed to measure the relative protein. Reactive oxygen species (ROS) and intracellular Ca2+ were assessed via fluorescence microscope, and the mitochondrial transmembrane potential was monitored by JC-10 staining. Results Our in vitro study revealed that mice in the ApoE-/- group compared with control mice showed higher Piezo1 expression(P

BackgroundAs a common clinical symptom, insomnia has a high incidence of combined mental illness and it is also a risk factor for the development of depression, anxiety and suicide. As a new concept in the field of health in recent years, mindfulness therapy can improve insomnia, anxiety and depression, which is a new way to solve such diseases.ObjectiveThis study aims to systematically evaluate the effects of mindfulness compared with conventional treatment on scores of the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) in people with insomnia and anxiety-depressive symptoms.MethodsArticles published before October 2022 were searched from seven databases and included in randomized controlled trials (RCTs) to evaluate mindfulness therapy. The assessment tool of Cochrane bias risk was used to evaluate the methodological quality of the literature. The main outcome indicators were HAMD and HAMA scores, and the secondary outcome indicators were SDS and SAS scores.ResultsTen randomized controlled trials including 1,058 subjects were systematically evaluated and meta-analyzed in this study. In the main outcome indicators, there was a significant difference between mindfulness therapy and conventional treatment in reducing HAMD score (MD: −3.67, 95% CI: −5.22–2.11, p

Abstract Objective N6-methyladenosine (m6A) mRNA modification triggers malignant behaviors of tumor cells and thereby drives malignant progression in gastric cancer (GC). However, data regarding the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in GC are very limited in the literature. We aimed to investigate the prognostic potential of m6A-related lncRNAs in predicting prognosis and monitoring immunotherapy efficacy in GC patients. Methods Transcriptome and clinical data were obtained from GC biopsies from Cancer Genome Atlas (TCGA). M6A-related lncRNAs associated with GC were identified by constructing a co-expression network, and the gene pairs differentially expressed in GC were selected using univariate analysis. We constructed a risk model based on prognosis-related lncRNA pairs selected using the LASSO algorithm and quantified the best cutoff by comparing the area under the curve (AUC) for risk stratification. A risk model with the optimal discrimination between high- and low-risk GC patients was established. Its feasibility for overall survival prediction and discrimination of clinicopathological features, tumor-infiltrating immune cells, and biomarkers of immune checkpoint inhibitors between high- and low-risk groups were assessed. Results Finally, we identified 11 m6A-related lncRNA pairs associated with GC prognosis based on transcriptome analysis of 375 GC specimens and 32 normal tissues. A risk model was constructed with an AUC of 0.8790. We stratified GC patients into high- and low-risk groups at a cutoff of 1.442. As expected, patients in the low-risk group had longer overall survival versus the high-risk group. Infiltration of cancer-associated fibroblasts, endothelial cells, macrophages, particularly M2 macrophages, and monocytes was more severe in high-risk patients than low-risk individuals, who exhibited high CD4+ Th1 cell infiltration in GC. Altered expressions of immune-related genes were observed in both groups. PD-1 and LAG3 expressions were found higher in low-risk patients than high-risk patients. Immunotherapy, either single or combined use of PD-1 or CTLA4 inhibitors, had better efficacy in low-risk patients than high-risk patients. Conclusion The new risk model based on a 11-m6A-related lncRNA signature can serve as an independent predictor for GC prognosis prediction and may aid in the development of personalized immunotherapy strategies for patients.

Abstract Breeding rice (Oryza sativa L.) with high yield, superior quality, desired grain shape and high resistance is the goal of breeding to meet the needs of current consumers. It is usually hard to combine multiple complex traits based on traditional breeding methods because they are frequently antagonistic to each other. However, molecular design breeding, as a novel breeding method, is an optional alternative to this challenge. To demonstrate molecular design breeding, 15 favorable genes from five parent lines were pyramided together to develop elite rice with high-yield, superior-quality, desired grain shape and high resistance to brown planthopper (BPH). The parental lines were 9311, the recurrent parent, carrying APO1, Ghd7, Ghd8 and Gn1a for high yield, GS3 and qSW5 for grain shape, and Wx and ALK for eating and cooking quality; 1880 with Gn8.1 for large panicles; Luo-Yu-Xiang carrying GW7 for grain shape and SBE3, SSIV2 and SSIII for eating and cooking quality; Luoyang6 with Bph6 and Luoyang9 with Bph9 for BPH resistance. After careful screening for the 15 targeted genes, desired phenotype and maximum genetic background from 9311, three molecular design lines with desired phenotypes, named as MD1 (Molecular design 1), MD2 and MD3 were developed. MD3 carried all 15 targeted genes, and MD1 and MD2 had 14 of the 15 targeted genes. Only SBE3 was not introgressed into MD1 and MD2 but this had minimal impact on the gel consistency and alkali spreading value. These newly bred lines exhibited higher yield potential, better grain quality with slender grains, low amylose content, high gel consistency and alkali spreading value, and higher BPH resistance compared to the parent 9311. In this study, we successfully created three novel rice lines with high yield, superior quality and improved BPH resistance by rational molecular design. Our results demonstrate molecular design is a powerful strategy to improve multiple complex traits and will provide a reference for the future commercial rice improvement.