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We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers—GPX4, RBM4, TPM3, PFKFB2, and PGAM5—and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

Abstract Based on limited theoretical applicability of metropolitan area concept under China’s circumstances and the planning practice in Greater Shanghai Metropolitan Area, this article proposes a Chinese understanding on the concept of “Metropolitan Area”, which extends its core connotation from a commuting area to a multi-functional area. It further proposes to utilize the preparation of spatial plans as means to promote high-quality development of metropolitan areas and to achieve coordinated regional development. Metropolitan area planning takes spatial planning as its basic attribute, and simultaneously embodies the contents of economic and social arrangements. It could become a binding contract based on consensus among member cities. In terms of technical innovations in planning practice, this article firstly suggests using a “problem-based, goal-targeted, action-driven, space-oriented and implementation-guided” approach to form a framework of “objective (indicator)-strategy-action-mechanism” to realize collaborative goals. Secondly, the spatial plan should focus on “bottom line factors” as well as “collaborative factors”, establishing a technical framework for regional spatial organization from multiple dimensions such as ecological pattern, city function, spatial structure, and conduction mechanism which drive transformations in regional governance modes.

Abstract The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H2O2 to •OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.

The flesh color of pummelo (Citrus maxima) fruits is highly diverse and largely depends on the level of carotenoids, which are beneficial to human health. It is vital to investigate the regulatory network of carotenoid biosynthesis to improve the carotenoid content in pummelo. However, the molecular mechanism underlying carotenoid accumulation in pummelo is not fully understood. In this study, we identified a novel histone methyltransferase gene, CgSDG40, involved in carotenoid regulation by analyzing the flesh transcriptome of typical white-fleshed pummelo, red-fleshed pummelo and extreme-colored F1 hybrids from a segregated pummelo population. Expression of CgSDG40 corresponded to flesh color change and was highly coexpressed with CgPSY1. Interestingly, CgSDG40 and CgPSY1 are located physically adjacent to each other on the chromosome in opposite directions, sharing a partially overlapping promoter region. Subcellular localization analysis indicated that CgSDG40 localizes to the nucleus. Overexpression of CgSDG40 significantly increased the total carotenoid content in citrus calli relative to that in wild type. In addition, expression of CgPSY1 was significantly activated in overexpression lines relative to wild type. Taken together, our findings reveal a novel histone methyltransferase regulator, CgSDG40, involved in the regulation of carotenoid biosynthesis in citrus and provide new strategies for molecular design breeding and genetic improvement of fruit color and nutritional quality.

Abstract Background Green foxtail [Setaria viridis (L.)] is one of the most abundant and troublesome annual grass weeds in alfalfa fields in Northeast China. Synthetic auxin herbicide is widely used in agriculture, while how auxin herbicide affects tillering on perennial grass weeds is still unclear. A greenhouse experiment was conducted to examine the effects of auxin herbicide 2,4-D on green foxtail growth, especially on tillers. Results In the study, 2,4-D isooctyl ester was used. There was an inhibition of plant height and fresh weight on green foxtail after application. The photosynthetic rate of the leaves was dramatically reduced and there was an accumulation of malondialdehyde (MDA) content. Moreover, applying 2,4-D isooctyl ester significantly reduced the tillering buds at rates between 2100 and 8400 ga. i. /ha. Transcriptome results showed that applying 2,4-D isooctyl ester on leaves affected the phytohormone signal transduction pathways in plant tillers. Among them, there were significant effects on auxin, cytokinin, abscisic acid (ABA), gibberellin (GA), and brassinosteroid signaling. Indeed, external ABA and GA on leaves also limited tillering in green foxtail. Conclusions These data will be helpful to further understand the responses of green foxtail to 2, 4-D isooctyl ester, which may provide a unique perspective for the development and identification of new target compounds that are effective against this weed species.

Abstract Under the requirements of modernized spatial governance and the national strategy for the integrated development of the Yangtze River Delta, the Shanghai Metropolitan Area has taken the lead in exploring collaborative governance in regional spatial planning, which aims to promote spatially coordinated governance and high-quality integrated development in metropolitan areas. This exploration focuses on the preparation and organizational innovation in regional planning, the combination of top and bottom organizational approaches, the importance of equal consultation during the planning process, the establishment of an open platform in the positioning of the planning, and the need for joint determination in planning approval. This exploration also discusses the innovative implementation of spatial planning cooperation through eight systematic actions and five space sector actions and defines the implementation focus through the immediate plan of action at the implementation level. The exploration of the “Spatial Cooperative Plan of the Greater Shanghai Metropolitan Area” demonstrates that the process and result of planning are equally important. Achieving consensus through plan making and fostering synergies through plan implementation are feasible paths for efficient collaborative governance in the Shanghai Metropolitan Area and other metropolitan areas in China.

Abstract Background Gastric cancer (GC) remains a malignant tumor with high morbidity and mortality, accounting for approximately 1,080,000 diagnosed cases and 770,000 deaths worldwide annually. Disulfidptosis, characterized by the stress-induced abnormal accumulation of disulfide, is a recently identified form of programmed cell death. Substantial studies have demonstrated the significant influence of immune clearance on tumor progression. Therefore, we aimed to explore the intrinsic correlations between disulfidptosis and immune-related genes (IRGs) in GC, as well as the potential value of disulfidptosis-related immune genes (DRIGs) as biomarkers. Methods This study incorporated the single-cell RNA sequencing (scRNA-seq) dataset GSE183904 and transcriptome RNA sequencing of GC from the TCGA database. Disulfidptosis-related genes (DRGs) and IRGs were derived from the representative literature on both cell disulfidptosis and immunity. The expression and distribution of DRGs were investigated at the single-cell level in different GC cell types. Pearson correlation analysis was used to identify the IRGs closely related to disulfidptosis. The prognostic signature of DRIGs was established using Cox and LASSO analyses. We then analyzed and evaluated the differences in long-term prognosis, Gene Set Enrichment Analysis (GSEA), immune infiltration, mutation profile, CD274 expression, and response to chemotherapeutic drugs between the two groups. A tissue array containing 63 paired GC specimens was used to verify the expression of 4 DRIGs and disulfidptosis regulator SLC7A11 through immunohistochemistry staining. Results The scRNA-seq analysis found that SLC7A11, SLC3A2, RPN1 and NCKAP1 were enriched in specific cell types and closely related to immune infiltration. Four DIRGs (GLA, HIF-1α, VPS35 and CDC37) were successfully identified to establish a signature to potently predict the survival time of GC patients. Patients with high risk scores generally experienced worse prognoses and exhibited greater resistant to classical chemotherapy drugs. Furthermore, the expression of GLA, HIF-1α, VPS35, CDC37 and SLC7A11 were elevated in GC tissues. A high expression of GLA, HIF-1α, VPS35 or CDC37 was associated with more advanced clinical stage of GC and increased SLC7A11 expression. Conclusion Current study first highlights the potential value of DRIGs as biomarkers in GC. We successfully constructed a robust model incorporating four DRIGs to accurately predict the survival time and clinicopathological characteristics of GC patients.

In this study, a fluorescence detection method combining aptamer-modified up-conversion nanoparticles (UCNPs) and magnetic nanoparticles (MNPs) was developed for detection of Clenbuterol (CLB). The aptamer-modified magnetic NPs captured CLB, which reacted with the aptamer-modified UCNPs and generated a sandwich complex. The aptamer-modified UCNPs acted as a fluorescence source. The MNP-CLB-UCNP complex was retrieved from the solution using an magnetic field, and the fluorescence intensity was detected by fluorescence spectrophotometry with excitation and emission spectra at 980 nm and in the 400–800 nm region, respectively. The results showed that the fluorescence intensity gradually increased with increasing concentrations of CLB with a good specify. The method was highly sensitive for the quantification of CLB, with a limit of detection of 0.304 ng mL−1. The recovery rate of CLB from pork samples ranged from 84 % to 94.87 %. This fluorescence method enables the sensitive, precise, and accurate quantification of CLB residues in pork samples.

ABSTRACT The lasso peptide microcin J25 (MccJ25) possesses strong antibacterial properties and is considered a potential effective component of bacterial disease treatment drugs and safe food preservatives. Although MccJ25 can be heterologously expressed in Bacillus subtilis as we have previously reported, its regulation and accumulation are yet to be understood. Here, we investigated the expression level and stability of MccJ25 in B. subtilis strains with disruption in peptidase genes pepA, pepF, and pepT. Oligoendopeptidase F (PepF) was found to be involved in reduction of the production of MccJ25 by degradation of its precursor peptide. In the pepF mutant, the MccJ25 reached a concentration of 1.68 µM after a cultivation time exceeding 60 hours, while the wild-type strain exhibited a concentration of only 0.14 µM. Moreover, the production of MccJ25 in B. subtilis downregulated the genes associated with sporulation, and this may contribute to its accumulation. Finally, this study provides a strategy to improve the stability and production of MccJ25 in B. subtilis.IMPORTANCEMccJ25 displays significant antibacterial activity, a well-defined mode of action, exceptional safety, and remarkable stability. Hence, it presents itself as a compelling candidate for an optimal antibacterial or anti-endotoxin medication. The successful establishment of exogenous production of MccJ25 in Bacillus subtilis provides a strategy for reducing its production cost and diversifying its utilization. In this study, we have provided evidence indicating that both peptidase PepF and sporulation are significant factors that limit the expression of MccJ25 in B. subtilis. The ΔpepF and ΔsigF mutants of B. subtilis express MccJ25 with higher production yield and enhanced stability. To sum up, this study developed several better engineered strains of B. subtilis, which greatly reduced the consumption of MccJ25 during the nutrient depletion stage of the host strain, improved its production, and elucidated factors that may be involved in reducing MccJ25 accumulation in B. subtilis.

IntroductionWeeds are significant factors that detrimentally affect crop health and hinder optimal herbage yield. Rhizosphere microorganisms play crucial roles in plant growth, development, and nutrient uptake. Therefore, research focusing on weed control through the lens of microorganisms has emerged as a prominent area of study. The oil-producing fungus Mortierella, which is known for its numerous agricultural benefits, has garnered significant attention in recent years.MethodsIn this study, we conducted inoculation experiments in a controlled artificial culture climate chamber to investigate the effects of differential hormones and differentially expressed genes in the stems and leaves of Digitaria sanguinalis using Liquid Chromatography Tandem Mass Spectrometry and RNA-seq techniques, respectively. Additionally, Pearson’s correlation analysis was used to establish correlations between differential hormones and growth indicators of Digitaria sanguinalis.Results and discussionThe results demonstrated that inoculation with Mortierella sp. MXBP304 effectively suppressed aboveground biomass and plant height in Digitaria sanguinalis. Furthermore, there was significant upregulation and downregulation in the expression of genes involved in the synthesis and metabolism of phenylalanine and L-phenylalanine. Conversely, the expression of genes related to tryptophan, L-tryptophan, and indole was significantly downregulated. The addition of Mortierella sp. MXBP304 can influence the gene expression associated with phenylalanine and tryptophan synthesis and metabolism during Digitaria sanguinalis growth, subsequently reducing the relative contents of phenylalanine and tryptophan, thereby directly inhibiting Digitaria sanguinalis growth.

ABSTRACT: Infectious coryza (IC) is an acute infectious respiratory disease in chickens that is caused by Avibacterium paragallinarum (A. paragallinarum). A. paragallinarum poses a significant threat to poultry health due to its virulence and multidrug resistance. This study isolated and identified 21 A. paragallinarum isolates from Guangdong between 2022 and 2023. Biochemical tests showed that 100% of A. paragallinarum isolates fermented glucose but did not ferment alginate and galactose, and only YZ18 was nicotinamide adenine dinucleotide independent. To determine the genetic relatedness between these isolates and NCBI reference strains, whole-genome-based phylogenetic analysis was employed. In addition, analysis of the 2,000 bp-length hmtp210 gene showed that the hmtp210 gene was strongly associated with A. paragallinarum serotypes. Meanwhile, a PCR assay for serotyping A. paragallinarum was developed based on the hmtp210 gene, this assay has high sensitivity and specificity. The antimicrobial susceptibility of isolates was assessed using the disk diffusion method. The antibiotic resistance genes of isolates were analyzed using the genomic method. Phenotypic resistance to ampicillin (95.2%), streptomycin (95.2%), methotrexate-sulfamethoxazole (90.5%), and tetracycline (85.7%) was most frequent among the isolates. All of the isolates exhibited resistance to multiple drugs, and furthermore, the isolates possessed a collective total of 14 genes associated with antibiotic resistance. This study will contribute to advancing our knowledge of A. paragallinarum antibiotic resistance and provide a scientific basis for the prophylaxis and treatment of IC, and the subsequent rational design of potential clinical therapeutics.

Abstract Background and purpose Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis. Methods GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan–Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients. Results Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan–Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression. Conclusions Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential. Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

The mass concentration of atmospheric particulate matter (PM) has been continuously decreasing in the Beijing-Tianjin-Hebei region. However, health endpoints do not exhibit a linear correlation with PM mass concentrations. Thus, it is urgent to clarify the prior toxicological components of PM to further improve air quality. In this study, we analyzed the long-term oxidative potential (OP) of water-soluble PM2.5, which is generally considered more effective in assessing hazardous exposure to PM in Beijing from 2018 to 2022 based on the dithiothreitol assay and identified the crucial drivers of the OP of PM2.5 based on online monitoring of air pollutants, receptor model, and random forest (RF) model. Our results indicate that dust, traffic, and biomass combustion are the main sources of the OP of PM2.5 in Beijing. The complex interactions of dust particles, black carbon, and gaseous pollutants (nitrogen dioxide and sulfur dioxide) are the main factors driving the OP evolution, in particular, leading to the abnormal rise of OP in Beijing in 2022. Our data shows that a higher OP is observed in winter and spring compared to summer and autumn. The diurnal variation of the OP is characterized by a declining trend from 0:00 to 14:00 and an increasing trend from 14:00 to 23:00. The spatial variation in OP of PM2.5 was observed as the OP in Beijing is lower than that in Shijiazhuang, while it is higher than that in Zhenjiang and Haikou, which is primarily influenced by the distribution of black carbon. Our results are of significance in identifying the key drivers influencing the OP of PM2.5 and provide new insights for advancing air quality improvement efforts with a focus on safeguarding human health in Beijing.

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease with intestinal tract as the main site. The pathogenic of UC has not yet been clarified, and multiple mechanisms can lead to the pathogenesis of UC. Traditional Chinese medicine (TCM) offers an opportunity for UC treatment. TCM has become the preferred treatment for UC with characteristics of multiple targets, multiple pathways and high safety. This review attempted to summarize the characteristics of TCM (compound prescriptions, single Chinese herbs, and active ingredients) for UC treatment and discussed their pathogenesis based on analyzing the UC-related gut microbiota, signaling pathway and cytokine. In order to provide more systematic and diverse reference for TCM in the prevention and treatment of UC, and provide theoretical reference for clinical treatment of UC. Materials and methods: The information was acquired from different databases, including Web of Science, PubMed, CNKI, Wanfang, and VIP databases. We then focused on the recent research progress in UC treatment by TCM. Finally, the deficiencies and future perspectives are proposed. Results: Modern pharmacological studies have shown that the compound prescriptions (strengthening spleen, clearing heat and removing dampness, clearing heat and removing toxin), single Chinese herbs (replenishing Qi, clearing heat, tonifying blood, etc.), and active ingredients (alkaloids, polysaccharides, flavonoids, polyphenols, terpenes, etc.) have an efficiency in UC treatment by regulating gut microbiota, signaling pathway and cytokine. Conclusions: TCM can achieve its purpose of UC prevention and treatment by acting in multiple ways, and TCM deserves further research and development in this field.

Blue honeysuckle seeds are often overlooked by the processing industry, but they are a good source of healthy oil. The composition, volatiles, and antioxidant capacity of blue honeysuckle seeds and seed oil were investigated for the first time. The fatty acid profile of the seed oil was analysed using GC–MS. The seed oil was particularly rich in polyunsaturated fatty acid, especially linoleic acid (71.24 ± 1.64 %). HS-SPME-GC–MS analysis temporarily detected 34 and 37 volatiles in the seeds and seed oil, respectively. Notably, aldehydes were identified as the major contributors to the aroma. The phytosterols, tocopherols, and triglycerides were identified in the seed oil. Interestingly, the total phenolic content and antioxidant capacity of the seeds were found to be much higher than the seed oil. This study evaluates the nutritional profile and value of blue honeysuckle seed oil, and suggests that it can be used as new functional oil.

Licorice is extensively utilized in the food industry, and glycyrrhetinic acid is among the most critical active constituents in licorice. This ingredient has garnered increasing attention in recent years. In a previous study, we identified a new series of Glycyrrhetinic acid derivatives containing piperazine skeleton, using virtual screening techniques based on docking. In this study, we conducted further optimization of the lead compound 4c, with a focus on enhancing the hydrophobic interactions in the binding site to improve agonist efficacy for peroxisome proliferator-activated receptor γ (PPARγ). The obtained compounds were characterized using 1H NMR, 13C NMR, HRMS, and HPLC. Furthermore, these compounds were evaluated strong antitumor activity. Some compounds with potent antitumor activities were tested for their PPARγ agonist activity. Especially, compound 4f showed the most potent antitumor activity with half maximal inhibitory concentration (IC50) values of 2.382 μM against the tested tumor cell lines Siha. Docking simulation was performed to position compound 4f into the PPARγ active site to determine the probable binding conformation. Consequently, we discovered a novel PPARγ agonist 4f that demonstrated high in vitro agonist activity.

Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

ABSTRACT: Milk-clotting enzyme (MCE) is the essential active agents in dairy processing. The traditional MCE is mainly obtained from animal sources, in which calf rennet is the most widely used in cheese industry. Traditional MCE substitute is becoming necessary due to its limited production and increased cheese consumption. A novel traditional MCE substitute was produced from Bacillus velezensis DB219 in this study. The DB219 MCE exhibited a notable specific activity of 6,110 Soxhlet units/mg and 3.16-fold purification yield with 28.87% recovery through ammonium sulfate fractionation and DEAE-Sepharose Fast Flow. The purified DB219 MCE was a metalloprotease with a molecular weight of 36 kDa. The DB219 MCE was weak acid resistance and stable at pH 6.0 to 10.0 and temperature

Foxtail millet is a drought-tolerant cereal and forage crop. The basic leucine zipper (bZIP) gene family plays important roles in regulating plant development and responding to stresses. However, the roles of bZIP genes in foxtail millet remain largely uninvestigated. In this study, 92 members of the bZIP transcription factors were identified in foxtail millet and clustered into ten clades. The expression levels of four SibZIP genes (SibZIP11, SibZIP12, SibZIP41, and SibZIP67) were significantly induced after PEG treatment, and SibZIP67 was chosen for further analysis. The studies showed that ectopic overexpression of SibZIP67 in Arabidopsis enhanced the plant drought tolerance. Detached leaves of SibZIP67 overexpressing plants had lower leaf water loss rates than those of wild-type plants. SibZIP67 overexpressing plants improved survival rates under drought conditions compared to wild-type plants. Additionally, overexpressing SibZIP67 in plants displayed reduced malondialdehyde (MDA) levels and enhanced activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) under drought stress. Furthermore, the drought-related genes, such as AtRD29A, AtRD22, AtNCED3, AtABF3, AtABI1, and AtABI5, were found to be regulated in SibZIP67 transgenic plants than in wild-type Arabidopsis under drought conditions. These data suggested that SibZIP67 conferred drought tolerance in transgenic Arabidopsis by regulating antioxidant enzyme activities and the expression of stress-related genes. The study reveals that SibZIP67 plays a beneficial role in drought response in plants, offering a valuable genetic resource for agricultural improvement in arid environments.

Ulcerative colitis (UC) is a chronic inflammatory disease, the incidence of which is increasing worldwide. However, the etiology and pathogenesis of UC remains unclear. The n-butanol extract of Pulsatilla decoction (BEPD), a traditional Chinese medicine, has been shown to be effective in treating UC. This study aimed to explore the molecular mechanism underlying the effects of BEPD on UC, in particular its effects on neutrophil extracellular trap (NET) formation by neutrophils. High-performance liquid chromatography was used to determine the principal compounds of BEPD. UC was induced in mice using dextran sodium sulfate, and mice were treated with 20, 40, or 80 mg/kg BEPD daily for seven days. Colonic inflammation was determined by assessing the disease activity index, histopathology, colonic mucosal damage index, colonic mucosal permeability, and pro- and anti-inflammatory cytokine levels. The infiltration and activation status of neutrophils in the colon were determined by analyzing the levels of chemokine (C-X-C motif) ligand (CXCL) 1 and CXCL2, reactive oxygen species, Ly6G, and numerous NET proteins. The findings suggest that BEPD improved the disease activity index, histopathology, and colonic mucosal damage index scores of mice with UC, and restored colonic mucosal permeability compared with untreated mice. The expression levels of the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in colon tissues were significantly decreased, while the expression levels of anti-inflammatory cytokines in colon tissues were significantly increased, exceeding those of control mice. In addition, BEPD reduced the expression of the neutrophil chemokines CXCL1 and CXCL2 in the colon tissue of mice with UC, reduced neutrophil infiltration, reduced reactive oxygen species levels, and significantly reduced the expression of NET proteins. BEPD also significantly reduced NET formation. The results of this study suggest that BEPD exerts therapeutic effects in a murine model of UC by inhibiting neutrophil infiltration and activation in the colon, as well as by inhibiting the expression of key proteins involved in NET formation and reducing NET formation, thereby alleviating local tissue damage and disease manifestations.

Dietary nutrition plays a crucial role in determining pregnancy outcomes, with poor diet being a major contributor to pregnancy metabolic syndrome and metabolic disorders in offspring. While carbohydrates are essential for fetal development, the excessive consumption of low-quality carbohydrates can increase the risk of pregnancy complications and have lasting negative effects on offspring development. Recent studies not only highlighted the link between carbohydrate intake during pregnancy, maternal health, and offspring well-being, but also suggested that the quality of carbohydrate foods consumed is more critical. This article reviews the impacts of low-carbohydrate and high-carbohydrate diets on pregnancy complications and offspring health, introduces the varied physiological effects of different types of carbohydrate consumption during pregnancy, and emphasizes the importance of both the quantity and quality of carbohydrates in nutritional interventions during pregnancy. These findings may offer valuable insights for guiding dietary interventions during pregnancy and shaping the future development of carbohydrate-rich foods.

Quinolone antibiotic residues present a high risk for food safety and have gained widespread attention. Nanomaterials based sensors have the advantages of on-site application, sensitivity, and small sample volume requirement and has attracted significant interest in on-site detection technology research for quinolone antibiotics. This paper introduces the application of optical sensors including fluorescence, colorimetry, SERS, ICA and electrochemical sensors based on diverse nanomaterials in quinolone antibiotics detection and summarizes the characteristics of diverse sensors. The application of nanomaterials including quantum dots and upconversion in optical sensors, as well as those of carbon and metal nanomaterials and redox media in electrochemical sensors are reviewed and evaluated. The objective of this work is to provide new concepts for antibiotics detection in food and the development of sensors.

Thirty-four known species and subspecies of the genus Antocha Osten Sacken, 1860 have been recorded from China, of which four occur in Tibet. Herein, two new Antocha species, A. (Antocha) curvativa sp. nov. and A. (A.) tibetana sp. nov., are described and illustrated from Tibet. The new species are distinguished from congeners mainly by their male genitalia. Antocha (A.) spiralis Alexander, 1932 and A. (A.) setigera Alexander, 1933, which are newly recorded in Tibet, are redescribed and illustrated. A key to Antocha species in the Qinghai-Tibet region of China is also presented.

Cultivated grasslands are an important part of grassland ecosystems and have been proven to be major carbon sinks, then playing an important role in the global carbon balance. The effect of cultivated grassland type (Medicago sativa, Triticum aestivum, Secale cereale, and Vicia villosa grasslands) on carbon flux (including net ecosystem CO2 exchange (NEE), ecosystem respiration (ER), and gross ecosystem productivity (GEP)) downstream of the Yellow River was studied via the static chamber technique and a portable photosynthetic system. Bare land was used as a control. The results showed that the four cultivated grassland types were mainly carbon sinks, and bare land was a carbon source. The cultivated grassland types significantly affected carbon flux. The average NEE and GEP of the grassland types were in the following order from high to low: Medicago sativa, Secale cereale, Triticum aestivum, and Vicia villosa grassland. Stepwise regression analysis showed that among all measured environmental factors, soil pH, soil bulk density (BD), soil organic carbon (SOC), and soil microbial carbon (MBC) were the main factors affecting CO2 flux. The combined influence of soil BD, SOC, and pH accounted for 77.6% of the variations in NEE, while soil BD, SOC, and MBC collectively explained 79.8% of changes in ER and 72.9% of the changes in GEP. This finding indicates that Medicago sativa grassland is a cultivated grassland with a high carbon sink level. The changes in carbon flux were dominated by the effects of soil physicochemical properties.

Although weeds can be inhibited by high planting densities, canopy shading, elemental balance and soil microbial recruitment are not yet adequately considered when measuring competitive effects on weed control. The effects of oat (Avena sativa) planting density (60 to 600 plants m−2) on the biomass and shoot element balance of oat and weeds were evaluated in a field experiment. The shift in the microbial community of the dominant weed species was examined in a pot experiment by growing the weed alone and in competition with 360 oat plants m−2 (recommended planting density) under greenhouse conditions. Increasing oat planting density beyond 360 plants m−2 did not improve oat forage yield or weed suppression. Compared to 60 plants m−2, the biomass of broadleaf and grass weeds decreased by 1122% and 111%, respectively, at a density of 360 plants m−2, while oat forage biomass increased by 60% and leaf area index by 24%. The improved canopy properties suppressed competing weeds through increased shading. Typically, the C:N and C:P ratios of shoots of Echinochloa crus-galli and Digitaria sanguinalis were higher than those of Portulaca oleracea and Chenopodium album. At high planting densities, E. crus-galli and D. sanguinalis exhibited high P contents and low N:P ratios, suggesting a limited supply of N nutrients for growth. Soil bacterial community assay showed that the composition of microbial communities of the two grass weeds were shaped by the presence of oat competition, which also considerably depleted several important functional microbes associated with nutrient cycling in the weeds’ rhizosphere. These results highlight that increased crop density significantly improves the crop competitive advantage over weeds through increased shading, reduced elemental balance, and beneficial microorganisms of weeds, thereby reducing the need for herbicides or physical weed control in oat cropping system.

Aflatoxin B1 (AFB1) is the most toxic mycotoxin contaminant, which is widely present in crops and poses a major safety hazard to animal and human health. To alleviate the cytotoxic effects of AFB1 on the intestine, we tested the protective effects of porcine β-defensin-2 (pBD-2). Results demonstrated that pBD-2 inhibited oxidative stress induced by AFB1 via decreasing the levels of ROS and enhancing the expression of antioxidant factors SOD-2 and NQO-1. In addition, pBD-2 attenuated AFB1-induced intestinal porcine epithelial cell line-J2 (IPEC-J2) injury through blocking mitochondria-mediated apoptosis. In vivo, pBD-2 treatment restored the intestinal mucosal structure and reduced the expression levels of apoptosis factors caspase-3 and Bax/Bcl-2. In conclusion, these results indicated that pBD-2 can alleviate AFB1-induced intestinal mucosal injury by inhibiting oxidative stress and mitochondria-mediated apoptosis. This study provides an effective strategy in developing pBD-2 as green feed additive to prevent AFB1 damage to animals.

Abstract Genome editing is an advanced genetic modification tool that facilitates the removal, insertion, or substitution of nucleotides in the genome of an organism for mutation induction. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9) is the most widely used genome editing tool that can precisely modify the specific sequence of a genome. Significant progress has been made in the use of CRISPR/Cas9 for the genetic improvement of food crops. However, in forage crops, the use of CRISPR/Cas9 is still in the infant stage with limited understanding and application. This article reviews current advances in the establishment and application of the CRISPR/Cas9 system in alfalfa, summarizes the application of CRISPR/Cas9 in several other forage legume and grass species, and discusses the prospects of CRISPR/Cas9 in the genetic improvement of forage crops.

Abstract The milk-clotting enzyme (MCE) is a crucial ingredient in cheese manufacture. Due to the limits of traditional MCE, finding viable substitute is a pressing issue. This study aims to isolate and identify a wild strain with high milk-clotting activity (MCA) and low proteolytic activity (PA) and optimize the fermentation conditions for MCE production. A strain of Bacillus velezensis DB219 with high MCA/PA value (9.2) was isolated from dairy soil (Wuchang, Heilongjiang, China) and identified through 16S rRNA from 40 strains. The optimal wheat bran, carbon, nitrogen, inoculum size, volume and initial pH were 60 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, 5%, 40 mL and 6.15, respectively for improving DB219 MCE production through single factor experiment. The wheat bran concentration, corn steep liquor concentration and volume were the most critical factor and their changed range was determined through Plackett–Burman design and the steepest ascent/descent experiments. The response surface analysis experiment of three factors and three levels was conducted by Box–Behnken design. The theoretical optimal fermentation conditions for DB219 MCE were as follows: wheat bran concentration 60.14 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, inoculum size 5%, volume 40.08 mL and initial pH 6.15. DB219 MCE achieved the maximal MCA (3164.84 SU/mL) that was 101.9% of the predicted value (3104.49 SU/mL) and 4.3-fold higher than the control.

Objective To investigate the viability of rapamycin-treated rapamycin-treated dendritic cells (DCs) in intervening transfusion-related acute lung injury (TRALI) after infection. Methods 1)The TRALI mouse model was induced by lipopolysaccharide (LPS) combined with anti-H2Kd antibody. The mice anal temperature and the wet/dry ratio of lung, kidney, spleen and brain tissues were measured. 2) Mouse bone marrow-derived DC cells were induced in vitro and treated with rapamycin (10nM) for 24h. 3) Mice were injected with or without rapamycin or rapamycin-treated DC, then injected with LPS intraperitoneally one hour later, finally injected with anti-H2Kd antibody 24 hours later to induce the onset of TRALI. The death situation of the mice was observed and recorded. The condition of mice after the onset of TRALI was analyzed by mouse body temperature, lung wet-dry ratio, and pleural effusion weight and lung histopathological sections. Results By comparing the induction effects of anti-H2Kd antibody solutions with different concentrations and volumes, the mouse model induced by 0.1mg/kg LPS combined with 4.5 mg/kg anti-H2Kd antibody (infusion volume of 100μL) was selected as the TRALI mouse model for this study. After the onset of TRALI, the wet/dry ratio of the lungs could be significantly increased and the body temperature could be significantly reduced in the model mice. After the intervention of TRALI mice with DCs treated with rapamycin, the mortality rate was significantly reduced, and the lung tissue lesions of the mice were significantly improved, whose protection effect was better than that of the rapamycin-treated group. Compared with the TRALI incidence group, the weight of pleural effusion in the intervention group was significantly reduced (P

Abstract Background Gastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence and development of GC is a complex process involving genetic changes in tumour cells and the influence of the surrounding tumour microenvironment (TME). Accumulative evidence shows that tumour‐associated macrophages (TAMs) play a vital role in GC, acting as plentiful and active infiltrating inflammatory cells in the TME. Main body In this review, the different functions and mechanisms of TAMs in GC progression, including the conversion of phenotypic subtypes; promotion of tumour proliferation, invasion and migration; induction of chemoresistance; promotion of angiogenesis; modulation of immunosuppression; reprogramming of metabolism; and interaction with the microbial community are summarised. Although the role of TAMs in GC remains controversial in clinical settings, clarifying their significance in the treatment selection and prognostic prediction of GC could support optimising TAM‐centred clinicaltherapy. Conclusion In summary, we reviewed the the phenotypic polarisation, function and molecular mechanism of TAMs and their potential applications in the treatment selection and prognostic prediction of GC.

Abstract Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long‐term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell‐cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single‐cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD effluent. We demonstrated that transforming growth factor‐β1 (TGF‐β1) can substitute for PD fluid to stimulate mesothelial cells releasing EVs, which in turn promoted fibroblast activation and peritoneal fibrogenesis. Blockade of EVs secretion by GW4869 or Rab27a knockdown markedly suppressed PD‐induced fibroblast activation and peritoneal fibrosis. Mechanistically, injured mesothelial cells produced EVs containing high level of integrin‐linked kinase (ILK), which was delivered to fibroblast and activated them via p38 MAPK signalling pathway. Clinically, the expression of ILK was up‐regulated in fibrotic peritoneum of patients undergoing long‐term PD. The percentage of ILK positive EVs in PD effluent correlated with peritoneal dysfunction and the degree of peritoneal damage. Our study highlights that peritoneal EVs mediate communications between mesothelial cells and fibroblasts to initiate peritoneal fibrogenesis. Targeting EVs or ILK could provide a novel therapeutic strategy to combat peritoneal fibrosis.

Evaluation of tubal patency is one of the vital steps in the process of female infertility management. Hysterosalpingo-contrast Sonography (HyCoSy) has become the first-line recommendation for evaluating tubal patency. However, there remain some controversies and dilemmas relevant to the evaluation of tubal patency by HyCosy, with no effective solution has been proposed or no consensus has been reached. Herein, combined with previous research and clinical experience, we conclude and analyze these controversies and dilemmas, aiming at offering our perspective on the opportunities and challenges which are faced by HyCosy.

Seed vigor is an important aspect of seed quality. It is critical to predict seed vigor and plant seedling emergence under diverse environmental conditions using the laboratory vigor test. Accordingly, laboratory experiments were conducted to determine the standard germination (SG), early individual counts of radicle emergence (RE), mean germination time (MGT), and vigor index (VI) for 16 commercially available seed lots of Siberian wildrye (Elymus sibiricus), an economically and ecological important grass species. The field emergence (FE) for seed lots was explored using a three-year field trial from 2021 to 2023. Meanwhile, pot experiments were carried out to determine the seedling emergence performance under different environmental conditions, including control, drought, and salinity stress. The correlation and regression analysis were done to investigate the links between laboratory vigor test with emergence performance under both field and pot conditions. The results showed that the SG of 16 seed lots were high, similar, and did not differ significantly between seed lots. However, the seedling emergence performance (emergence percentage, seedling dry weight, and simplified vigor index) differed significantly between seed lots under both field and pot conditions. The SG was not significantly correlated with seedling emergence performance under either the field or pot conditions. The counts of RE at selected timing, MGT, and VI showed a significant relationship with seed vigor as reflected by seedling emergence performance under diverse environmental conditions, and we found that RE at 108 h was highly predictive of seed vigor and seedling emergence. The RE at 108 h and VI were positively related to seed vigor, while MGT was negatively related. The seed lots with low vigor had lower RE at 108 h and VI but longer MGT. Overall, both RE at 108 h, MGT, and VI can be used to estimate seed vigor and predict seedling emergence under different environmental conditions, and we highly recommend RE at 108 h as a quick, precise, and convenient vigor test and early warning sign for seed storage of E. sibiricus. These results will enable seed researchers, plant breeders, farmers, and government program directors to target higher seed vigor more effectively for E. sibiricus and similar grass species.

Vibrio parahaemolyticus is a halophilic and heat-labile gram-negative bacterium and is the most prevalent foodborne bacterium in seafood. In order to develop a rapid and sensitive method for detecting the foodborne pathogenic bacterium Vibrio parahaemolyticus, an aptamer-modified magnetic nanoparticle and an aptamer-modified upconversion nanoparticle were synthesised and used as a capture probe and a signal probe, respectively. The aptamer-modified magnetic nanoparticle, V. parahaemolyticus cell, and aptamer-modified upconversion nanoparticle formed a sandwich-like complex, which was rapidly separated from a complex matrix using a magnetic force, and the bacterial concentration was determined by fluorescence intensity analysis. The results showed that the fluorescence intensity signal correlated positively with the concentration of V. parahaemolyticus in the range of 3.2 × 102 to 3.2 × 105 CFU/mL, with a linear equation of y = 296.40x − 217.67 and a correlation coefficient of R2 = 0.9610. The detection limit of the developed method was 4.4 CFU/mL. There was no cross-reactivity with other tested foodborne pathogens. This method is highly specific and sensitive for the detection of V. parahaemolyticus, and can achieve the qualitative detection of this bacterium in a complex matrix.

Abstract Background Red clover (Trifolium pratense L.) is a diploid perennial temperate legume with 14 chromosomes (2n = 14) native to Europe and West Asia, with high nutritional and economic value. It is a very important forage grass and is widely grown in marine climates, such as the United States and Sweden. Genetic research and molecular breeding are limited by the lack of high-quality reference genomes. In this study, we used Illumina, PacBio HiFi, and Hi-C to obtain a high-quality chromosome-scale red clover genome and used genome annotation results to analyze evolutionary relationships among related species. Results The red clover genome obtained by PacBio HiFi assembly sequencing was 423 M. The assembly quality was the highest among legume genome assemblies published to date. The contig N50 was 13 Mb, scaffold N50 was 55 Mb, and BUSCO completeness was 97.9%, accounting for 92.8% of the predicted genome. Genome annotation revealed 44,588 gene models with high confidence and 52.81% repetitive elements in red clover genome. Based on a comparison of genome annotation results, red clover was closely related to Trifolium medium and distantly related to Glycine max, Vigna radiata, Medicago truncatula, and Cicer arietinum among legumes. Analyses of gene family expansions and contractions and forward gene selection revealed gene families and genes related to environmental stress resistance and energy metabolism. Conclusions We report a high-quality de novo genome assembly for the red clover at the chromosome level, with a substantial improvement in assembly quality over those of previously published red clover genomes. These annotated gene models can provide an important resource for molecular genetic breeding and legume evolution studies. Furthermore, we analyzed the evolutionary relationships among red clover and closely related species, providing a basis for evolutionary studies of clover leaf and legumes, genomics analyses of forage grass, the improvement of agronomic traits.

BackgroundFor patients of primary brainstem hemorrhage (PBH), it is crucial to find a method that can quickly and accurately predict the correlation between status of consciousness and PBH.ObjectiveTo analyze the value of computer tomography (CT) signs in combination with artificial intelligence (AI) technique in predicting the correlation between status of consciousness and PBH.MethodsA total of 120 patients with PBH were enrolled from August 2011 to March 2021 according to the criteria. Patients were divided into three groups [consciousness, minimally conscious state (MCS) and coma] based on the status of consciousness. Then, first, Mann–Whitney U test and Spearman rank correlation test were used on the factors: gender, age, stages of intracerebral hemorrhage, CT signs with AI or radiology physicians, hemorrhage involving the midbrain or ventricular system. We collected hemorrhage volumes and mean CT values with AI. Second, those significant factors were screened out by the Mann–Whitney U test and those highly or moderately correlated by Spearman’s rank correlation test, and a further ordinal multinomial logistic regression analysis was performed to find independent predictors of the status of consciousness. At last, receiver operating characteristic (ROC) curves were drawn to calculate the hemorrhage volume for predictively assessing the status of consciousness.ResultsPreliminary meaningful variables include hemorrhage involving the midbrain or ventricular system, hemorrhage volume, grade of hematoma shape and density, and CT value from Mann–Whitney U test and Spearman rank correlation test. It is further shown by ordinal multinomial logistic regression analysis that hemorrhage volume and hemorrhage involving the ventricular system are two major predictors of the status of consciousness. It showed from ROC that the hemorrhage volumes of 6.225 mL correspond to consciousness, MCS or coma, respectively. If the hemorrhage volume is the same, hemorrhage involving the ventricular system should be correlated with more severe disorders of consciousness (DOC).ConclusionCT signs combined with AI can predict the correlation between status of consciousness and PBH. Hemorrhage volume and hemorrhage involving the ventricular system are two independent factors, with hemorrhage volume in particular reaching quantitative predictions.

A cross-sectional census was conducted on all students at the campus of Inner Mongolia Medical University using a self-administered questionnaire. This study aimed to investigate their love from psychological pressure, behavioral characteristics, social cognition, etc. Our results show that all students cultivate feelings and become lifelong partners as their motivation for love. Among the population with various demographic characteristics, the prevalence of love among disadvantaged groups is low; that is, women are lower than men, and those from rural are lower than those from cities. After balancing areas and gender, mental working families have a high prevalence of love. Instead, students whose parents' high expectations pressure their children to have a high love prevalence. This is due to China's specific historical perspective. Our results suggested that although China has been deeply integrated with the world and has more frequent ideological and cultural exchanges, college students still inherit China's traditional outlook on love.

Abstract Background Individual plants can identify their neighbors and adjust their biomass investment to avoid competing with their relatives or jointly cope with external stresses. Maternal effects can improve their offspring adaptability under external stresses. However, how grazing-induced maternal effects influence plant kin interactions remain unknown. Methods Clonal offspring of Leymus chinensis grown under multi-year grazing and non-grazing conditions were used for this study. A greenhouse experiment was conducted to evaluate the performance of focal plants in the presence of kin and stranger neighbors, with the aim of analyzing the interaction between maternal effect and kin relatedness. Results Kin relatedness of neighboring plants affected the biomass production and allocation of focal plants, demonstrating the presence of kin recognition in L. chinensis. Moreover, grazing-induced maternal effects significantly enhanced kin recognition in the species. Consequently, the presence of stranger neighbors significantly improved the growth potential of grazed offspring. Specifically, the total biomass of clonal offspring increased by 73.1% compared to the kin group, potentially buffering grazing-induced plant productivity declines. Conclusions This study shows that historical grazing enhances kin recognition in L. chinensis. Thus, introducing multi-genotypic plants can increase the productivity of grasslands. The findings of this study enhance our understanding of intraspecific plant–plant interactions in clonal species and provide new insights into sustainable grassland management.

Abstract Background Paspalum notatum ‘Flugge’ is a diploid with 20 chromosomes (2n = 20) multi-purpose subtropical herb native to South America and has a high ecological significance. It is currently widely planted in tropical and subtropical regions. Despite the gene pool of P. notatum ‘Flugge’ being unearthed to a large extent in the past decade, no details about the genomic information of relevant species in Paspalum have been reported. In this study, the complete genome information of P. notatum was established and annotated through sequencing and de novo assembly of its genome. Results The latest PacBio third-generation HiFi assembly and sequencing revealed that the genome size of P. notatum ‘Flugge’ is 541 M. The assembly result is the higher index among the genomes of the gramineous family published so far, with a contig N50 = 52Mbp, scaffold N50 = 49Mbp, and BUSCOs = 98.1%, accounting for 98.5% of the estimated genome. Genome annotation revealed 36,511 high-confidence gene models, thus providing an important resource for future molecular breeding and evolutionary research. A comparison of the genome annotation results of P. notatum ‘Flugge’ with other closely related species revealed that it had a close relationship with Zea mays but not close compared to Brachypodium distachyon, Setaria viridis, Oryza sativa, Puccinellia tenuiflora, Echinochloa crusgalli. An analysis of the expansion and contraction of gene families suggested that P. notatum ‘Flugge’ contains gene families associated with environmental resistance, increased reproductive ability, and molecular evolution, which explained its excellent agronomic traits. Conclusion This study is the first to report the high-quality chromosome-scale-based genome of P. notatum ‘Flugge’ assembled using the latest PacBio third-generation HiFi sequencing reads. The study provides an excellent genetic resource bank for gramineous crops and invaluable perspectives regarding the evolution of gramineous plants.

This study investigated the differences in stem and leaf growth characteristics of Medicago sativa and Bromus inermis in the Jiaozhou region of China during 2019–2020 under three different planting modes of the two forages: monoculture, mixed species sowing in the same rows, and mixed species sowing in alternating rows. No special management of the experimental plots was carried out in this study to simulate as much as possible the growth of forages in their natural state. The stem and leaf characteristics influencing the dry matter weight were calculated using grey correlation. These characteristics included leaf length, leaf width, leaf thickness, leaf area, leaf fresh weight, stem length, stem diameter, stem fresh weight, stem–leaf ratio, fresh matter yield, dry matter yield, and protein yield of M. sativa and B. inermis under different sowing methods in different years. The results showed that the weight pattern of the characteristics affecting the yield of M. sativa and B. inermis production was leaf area > stem diameter > leaf length > stem length > leaf width > leaf thickness, leaf area > leaf length > stem length > leaf width > leaf thickness > stem diameter. Considering all the growth factors, the production capacity was ranked as mixed sowing in alternating rows > mixed sowing in same rows > monoculture. Thus, the suitable mode for M. sativa–B. inermis sowing was mixed sowing in alternating rows.

Abstract OTUB2 is a deubiquitinating enzyme that contributes to tumor progression. However, the expression of OTUB2 and its prognostic importance in gastric cancer remain unclear. The expression of OTUB2 and KRT80 in GC tissues was investigated using western blotting, qRT-PCR, multiple immunofluorescence staining, and immunohistochemistry. For survival studies, Kaplan–Meier analysis with the log-rank test was used. The role of OTUB2 during GC proliferation was investigated using in vivo and in vitro assays. OTUB2 was found to be overexpressed in GC tissues and to act as an oncogene, which was linked to patients’ poor prognosis. Knockdown of OTUB2 inhibited the proliferative capacity of GC cells in vitro and in vivo, although the proliferative capacity was restored upon re-supplementation with KRT80. OTUB2 mechanically stabilized KRT80 by deubiquitinating and shielding it from proteasome-mediated degradation through Lys-48 and Lys-63. Furthermore, by activating the Akt signaling pathway, OTUB2 and KRT80 facilitated GC proliferation. In summary, OTUB2 regulates KRT80 stability via deubiquitination promoting proliferation in GC via activation of the Akt signaling pathway, implying that OTUB2 could be a novel prognostic marker.

Abstract Background Most of malignant melanomas originate from skin and often metastasize to the lungs, rarely metastasizes to the liver and bone. However, imageology characters of lung metastasis tumor are commonly similar to those of fungal infections. Case presentation A patient was admitted with unhealed plantar puncture wound for 3 years, and cough and expectoration for 2 years. The chest computed tomography (CT) revealed multiple nodules with cavities, and the patient was diagnosed of pulmonary fungal infection in another hospital and received antifungal therapy for more than 8 months, but the clinical symptoms and chest imaging findings continue to progress. After admission, the pathological results of both lung biopsy and biopsy of the plantar wound 3 years ago indicated malignant melanoma. Conclusions The diagnosis of lung lesions cannot rely solely on imaging diagnosis, lung biopsy should be performed if necessary.

Constructing a risk model with the subject of autonomous vehicles to screen out the vehicles of potential conflicts and analyze their choices under different strategies. Based on the co-simulation of Python and SUMO, establishing a model of on-ramp merge driving behaviour of autonomous vehicles based on non-cooperative static game. Under this model, the experiment results that the average speed in the merging area is increased by 12.7%, the standard deviation of the average speed is reduced by 35.46%, and the number of the vehicles successfully merged before the end of the merging area is 4.86 times that of traditional method, indicate that the model can effectively help the vehicles be merged and improve the traffic efficiency to a certain extent.

Since it will take time for vehicles to be fully automated, research on mixed traffic flow with different levels of vehicles will be the focus in the future. This paper takes L0, L1, L2, L3, L4, L5 vehicles as the research object, selects the Intelligent Diver Model (IDM), Adaptive Cruise Control (ACC) model, F-STCA model and LC2013 model to construct the vehicle's driving behaviour model, builds SUMO (Simulation of Urban Mobility) and Python co-simulation platform to conduct models simulation verification and safety analysis. The results show that: (1) The improved IDM model can realize the error caused by the heterogeneity of driver's personality; the improved ACC model can improve speed and keep a small change range with the interfering vehicle; the improved F-STCA model can expand the vehicle's lane-changing intention and reflect the driver's driving uncertainty. (2) The increase of penetration can increase the number of lane changes in basic sections, but in merging area, they are proportional at low density and inversely proportional at high density; penetration can reduce the occurrence of traffic conflicts and change the distribution of Time-To-Collision (TTC). This paper can predict the evolution law of traffic flow under the new technology, and provide a reference for future traffic planning and management.

BackgroundThe spleen is the largest peripheral lymphoid organ in the body. Studies have implicated the spleen in the development of cancer. However, it is unknown whether splenic volume (SV) is associated with the clinical outcome of gastric cancer.MethodsData of gastric cancer patients treated with surgical resection were retrospectively analyzed. Patients were divided into three groups: underweight, normal-weight and overweight. Overall survival was compared in patients with high and low splenic volume. The correlation between splenic volume and peripheral immune cells were analyzed.ResultsOf 541 patients, 71.2% were male and the median age was 60. Underweight, normal-weight and overweight patients accounted for 5.4%, 62.3% and 32.3%, respectively. High splenic volume was associated with unfavorable prognosis across the three groups. In addition, the increase of splenic volume during neoadjuvant chemotherapy was not associated with prognosis. The baseline splenic volume was negatively correlated with lymphocytes (r=-0.21, p

BackgroundWe aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).Research design and methodsWe searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software.ResultsPatients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,P = 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,P = 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38, P = 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P < 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P < 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,P < 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,P < 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71, P < 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities.ConclusionAlthough CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups.