The GhEB1C gene mediates resistance of cotton to Verticillium wilt.

MAIN CONCLUSION: The GhEB1C gene of the EB1 protein family functions as microtubule end-binding protein and may be involved in the regulation of microtubule-related pathways to enhance resistance to Verticillium wilt. The expression of GhEB1C is induced by SA, also contributing to Verticillium wilt resistance. Cotton, as a crucial cash and oil crop, faces a significant threat from Verticillium wilt, a soil-borne disease induced by Verticillium dahliae, severely impacting cotton growth and development. Investigating genes associated with resistance to Verticillium wilt is paramount. We identified and performed a phylogenetic analysis on members of the EB1 family associated with Verticillium wilt in this work. GhEB1C was discovered by transcriptome screening and was studied for its function in cotton defense against V. dahliae. The RT-qPCR analysis revealed significant expression of the GhEB1C gene in cotton leaves. Subsequent localization analysis using transient expression demonstrated cytoplasmic localization of GhEB1C. VIGS experiments indicated that silencing of the GhEB1C gene significantly increased susceptibility of cotton to V. dahliae. Comparative RNA-seq analysis showed that GhEB1C silenced plants exhibited altered microtubule-associated protein pathways and flavonogen-associated pathways, suggesting a role for GhEB1C in defense mechanisms. Overexpression of tobacco resulted in enhanced resistance to V. dahliae as compared to wild-type plants. Furthermore, our investigation into the relationship between the GhEB1C gene and plant disease resistance hormones salicylic axid (SA) and jasmonic acid (JA) revealed the involvement of GhEB1C in the regulation of the SA pathway. In conclusion, our findings demonstrate that GhEB1C plays a crucial role in conferring immunity to cotton against Verticillium wilt, providing valuable insights for further research on plant adaptability to pathogen invasion.

Global, regional, and national levels and trends in burden of urticaria: A systematic analysis for the Global Burden of Disease study 2019.

Background: Urticaria places a significant burden on individuals and society due to its widespread nature. The aim of this study was to evaluate the burden of urticaria in different regions and nations by analysing data from the Global Burden of Disease study 2019 (GBD 2019), with the goal of providing information to health care policymakers. Methods: By utilising data from the GBD 2019 database, this study analysed metrics such as incidence, prevalence, disability-adjusted life years (DALYs), age-standardised rate (ASR), and estimated annual percentage changes (EAPC) globally and across 204 countries and regions. The data was further stratified by age, sex, and sociodemographic index (SDI). Results: In 2019, global incidence cases, prevalence cases, and overall disease burden as measured by DALYs all increased. The distribution of the burden exhibited marked geographical heterogeneity. At the regional level, the burden is highest in Central and Eastern Europe and Central Asia, with the strongest growth in South Asia, compared with a decline in the high-income Asia Pacific. At the country level, Nepal reports the highest burden of urticaria, while Portugal has the lowest. Gender and age analyses showed that the burden of urticaria is higher in females than in males, with urticaria cases declining with age, especially in children, and picking up among the elderly. The study also finds a correlation between the burden of urticaria and the SDI, with the central part of the SDI showing a consistent increasing trend. Conclusion: This study found that the global burden of urticaria has risen from 1990 to 2019. Factors like geographic location, gender, and SDI influenced the urticaria burden. Overall, these results offer a resource to guide public health strategies seeking to reduce the burden of urticaria.

Functional Analysis of the GhIQD1 Gene in Cotton Resistance to Verticillium Wilt.

Cotton is a critical crop with massive economic implications worldwide. Verticillium wilt is a soil-borne ailment caused by Verticillium dahliae, which harms the growth and development of cotton. Therefore, investigating the genes associated with resistance to verticillium wilt is of particular significance. In this study, we identified the GhIQD1 gene through transcriptome analysis and experimentally characterized the role of the GhIQD1 gene in cotton against V. dahliae. The findings indicated that GhIQD1 acts as a calmodulin-binding protein. The expression of GhIQD1 was the highest in stems, and the expression level increased significantly following infection with V. dahliae. The expression in resistant cotton varieties was higher than in susceptible cotton varieties. Through overexpression of the GhIQD1 gene in tobacco, these transgenic plants exhibited improved resistance to V. dahliae. In contrast, by silencing the GhIQD1 gene in cotton through VIGS, the resistance to V. dahliae was reduced. Following inoculation, the leaves yellowed, and the disease index was higher. Transcriptome analysis of transgenic tobacco 72 h after inoculation indicated that overexpression of GhIQD1 increased the enrichment of the calmodulin pathway and stimulated the production of plant hormones alongside secondary metabolites. Consequently, we investigated the relationship between the GhIQD1 gene and plant disease-resistant hormones SA, JA, and ABA. In summary, this study uncovered the mechanism by which GhIQD1 conferred resistance to V. dahliae in cotton through positive regulation of JA and ABA, providing crucial information for further research on the adaptation of plants to pathogen invasion.

Chronic exposure to PM10 induces anxiety-like behavior via exacerbating hippocampal oxidative stress.

As one of the most environmental concerns, inhaled particulate matter (PM10) causes numerous health problems. However, the associations between anxiety behavior and toxicity caused by PM10 have rarely been reported so far. To investigate the changes of behavior after PM10 exposure and to identify the potential mechanisms of toxicity, PM10 samples (with doses of 15 mg/kg and 30 mg/kg) were intratracheally instilled into rats to simulate inhalation of polluted air by the lungs. After instillation for eight weeks, anxiety-like behavior was evaluated, levels of oxidative stress and morphological changes of hippocampus were measured. The behavioral results indicated that PM10 exposure induced obvious anxiety-like behavior in the open field and elevated plus maze tests. Both PM10 concentrations tested could increase whole blood viscosity and trigger hippocampal neuronal damage and oxidative stress by increasing superoxide dismutase (SOD) activities and malondialdehyde levels, and decreasing the expressions of antioxidant-related proteins (e.g., nuclear factor erythroid 2-related factor 2 (Nrf2), SOD1 and heme oxygenase 1). Furthermore, through collecting and analyzing questionnaires, the data showed that the participants experienced obvious anxiety-related emotions and negative somatic responses under heavily polluted environments, especially PM10 being the main pollutant. These results show that PM10 exposure induces anxiety-like behavior, which may be related to suppressing the Nrf2/Keap1-SOD1 pathway.

Genome-Wide Identification and Expression Analysis Unveil the Involvement of the Cold Shock Protein (CSP) Gene Family in Cotton Hypothermia Stress.

Cold shock proteins (CSPs) are DNA/RNA binding proteins with crucial regulatory roles in plant growth, development, and stress responses. In this study, we employed bioinformatics tools to identify and analyze the physicochemical properties, conserved domains, gene structure, phylogenetic relationships, cis-acting elements, subcellular localization, and expression patterns of the cotton CSP gene family. A total of 62 CSP proteins were identified across four cotton varieties (Gossypium arboreum, Gossypium raimondii, Gossypium barbadense, Gossypium hirsutum) and five plant varieties (Arabidopsis thaliana, Brassica chinensis, Camellia sinensis, Triticum aestivum, and Oryza sativa). Phylogenetic analysis categorized cotton CSP proteins into three evolutionary branches, revealing similar gene structures and motif distributions within each branch. Analysis of gene structural domains highlighted the conserved CSD and CCHC domains across all cotton CSP families. Subcellular localization predictions indicated predominant nuclear localization for CSPs. Examination of cis-elements in gene promoters revealed a variety of elements responsive to growth, development, light response, hormones, and abiotic stresses, suggesting the potential regulation of the cotton CSP family by different hormones and their involvement in diverse stress responses. RT-qPCR results suggested that GhCSP.A1, GhCSP.A2, GhCSP.A3, and GhCSP.A7 may play roles in cotton's response to low-temperature stress. In conclusion, our findings underscore the significant role of the CSP gene family in cotton's response to low-temperature stress, providing a foundational basis for further investigations into the functional aspects and molecular mechanisms of cotton's response to low temperatures.

Synergistic induction of tertiary lymphoid structures by chemoimmunotherapy in bladder cancer.

BACKGROUND: A substantial number of patients with bladder cancer fail to benefit from immune checkpoint inhibitors (ICIs). We aim to investigate whether the addition of other therapeutic modalities into immunotherapy may augment the immune reactivity, thereby improving the overall response rate. METHODS: We conducted a comprehensive assessment of the immunological changes following immunotherapy and chemotherapy, employing both single-cell RNA sequencing and bulk RNA sequencing analyses. RESULTS: The bladder cancer patient treated with ICIs exhibited a higher abundance of B cells and T follicular helper cells compared to the treatment-naïve patient. Analysis of public datasets and the in-house RJBLC-I2N003 cohort revealed the induction of tertiary lymphoid structure (TLS) neogenesis and maturation by immunotherapy. The IMvigor 210 study suggested that TLS could serve as a predictor of immunotherapy response and patient prognosis. In addition, genome-wide transcriptome data unveiled a shift towards the immune-enriched subtype over the desert subtype in patients receiving neoadjuvant chemotherapy. Notably, the proportions of CD20 + B cells, T follicular helper cells, and TLSs were significantly increased. In patients treated with a combination of neoadjuvant chemotherapy and ICIs, TLS positivity and maturity were improved compared to the baseline. Furthermore, neoadjuvant chemoimmunotherapy resulted in a higher rate of pathological complete response compared to monotherapies. CONCLUSIONS: This work pinpointed the individual effect of immunotherapy and chemotherapy in fostering TLS development, and underscored the superior effectiveness of combined modalities in enhancing TLS maturation and response rates.

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer. METHODS: Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein-protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole. RESULTS: Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways. CONCLUSIONS: We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer. SUBJECTS: Bioinformatics, Computational Biology, Molecular Biology.

Genome-wide identification and analyses of cotton high-affinity nitrate transporter 2 family genes and their responses to stress.

Nitrate transporters (NRTs) are crucial for the uptake, use, and storage of nitrogen by plants. In this study, 42 members of the GhNRT2 (Nitrate Transporter 2 family) were found in the four different cotton species. The conserved domains, phylogenetic relationships, physicochemical properties, subcellular localization, conserved motifs, gene structure, cis-acting elements, and promoter region expression patterns of these 42 members were analyzed. The findings confirmed that members of the NRT2 family behaved typically, and subcellular localization tests confirmed that they were hydrophobic proteins that were mostly located on the cytoplasmic membrane. The NRT2 family of genes with A.thaliana and rice underwent phylogenetic analysis, and the results revealed that GhNRT2 could be divided into three groups. The same taxa also shared similar gene structure and motif distribution. The composition of cis-acting elements suggests that most of the expression of GhNRT2 may be related to plant hormones, abiotic stress, and photoreactions. The GhNRT2 gene was highly expressed, mainly in roots. Drought, salt, and extreme temperature stress showed that GhNRT2 gene expression was significantly up-regulated or down-regulated, indicating that it may be involved in the stress response of cotton. In general, the genes of the NRT2 family of cotton were comprehensively analyzed, and their potential nitrogen uptake and utilization functions in cotton were preliminarily predicted. Additionally, we provide an experimental basis for the adverse stress conditions in which they may function.

Overexpression of the Caragana korshinskii com58276 Gene Enhances Tolerance to Drought in Cotton (Gossypium hirsutum L.).

The increasing water scarcity associated with environmental change brings significant negative impacts to the growth of cotton plants, whereby it is urgent to enhance plant tolerance to drought. Here, we overexpressed the com58276 gene isolated from the desert plant Caragana korshinskii in cotton plants. We obtained three OE plants and demonstrated that com58276 confers drought tolerance in cotton after subjecting transgenic seeds and plants to drought. RNA-seq revealed the mechanisms of the possible anti-stress response, and that the overexpression of com58276 does not affect growth and fiber content in OE cotton plants. The function of com58276 is conserved across species, improving the tolerance of cotton to salt and low temperature, and demonstrating its applicability to improve plant resistance to environmental change.

Identification of a six-gene prognostic signature for bladder cancer associated macrophage.

As major components of the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play an exceedingly complicated role in tumor progression and tumorigenesis. However, few studies have reported the specific TAM gene signature in bladder cancer. Herein, this study focused on developing a TAM-related prognostic model in bladder cancer patients based on The Cancer Genome Atlas (TCGA) data. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key genes related to TAM (M2 macrophage). Gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed the functional categories of the key genes. Simultaneously, we used the Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regressions to establish a TMA-related prognostic model containing six key genes: TBXAS1, GYPC, HPGDS, GAB3, ADORA3, and FOLR2. Subsequently, single-cell sequencing data downloaded from Gene Expression Omnibus (GEO) suggested that the six genes in the prognostic model were expressed in TAM specifically and may be involved in TAM polarization. In summary, our research uncovered six-TAM related genes that may have an effect on risk stratification in bladder cancer patients and could be regarded as potential TAM-related biomarkers.

Global, Regional, and National Burden of Urolithiasis from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

Introduction: To get insight into the temporal trends of urolithiasis, and thus decrease the health burden of urolithiasis, we comprehensively investigated the specific epidemiological indicators that varied among different countries and regions according to the diversity of geographic locations, gender, age, year, and socioeconomic status. Methods: In this study, we investigated the incidence, death, disability-adjusted life years (DALYs) of urolithiasis quantified by the number of patients, age-standardized rates, and estimated annual percentage changes based on geographic locations, gender, age, and year to decode the epidemiological characteristics using the data from 1990 to 2019 in the Global Burden of Disease database. Results: In 2019, more than 115 million (95% uncertainty interval [95% UI] 93-140) incident cases of urolithiasis occurred worldwide, and the age-standardized incidence rate (ASIR) (per 100,000 population) decreased from 1696.2 (1358.1-2078.1) in 1990 to 1394 (1126.4-1688.2) in 2019. Nearly 13,279 (95% UI: 10616-16267) died of urolithiasis, contributing to 0.6 million (0.5-0.7) DALYs in 2019. The highest age-standardized DALY rates (33.33 per 100 000 population) in 2019 were observed in Armenia, whereas the largest negative estimated annual percentage changes of DALYs were seen in Poland. The ASIR of males was higher than females. However, the ASIR EAPC of males was lower than females from 1990 to 2019. Males aged 50-54 years old were more likely to suffer from urolithiasis. Joinpoint regression model analyses suggested that the global age-standardized incidence and DALY rates of urolithiasis encountered a trend to decline over the past 30 years. Over the years, the attenuation of this disease was pinpointed to be weakly related to the Socio-demographic index. Conclusion: At the global level, both the incident and DALY cases experienced substantial growth compared to the absolute cases in 1990. However, global age-standardized incidence and DALY rate of urolithiasis were observed to decline from 1990 to 2019. Males' ASIR was higher than females, while the gap narrowed over the years. A weakly positive correlation between ASIR of urolithiasis and SDI was also observed in this study.

A Rapid and Efficient Method for Isolation and Transformation of Cotton Callus Protoplast.

Protoplasts, which lack cell walls, are ideal research materials for genetic engineering. They are commonly employed in fusion (they can be used for more distant somatic cell fusion to obtain somatic hybrids), genetic transformation, plant regeneration, and other applications. Cotton is grown throughout the world and is the most economically important crop globally. It is therefore critical to study successful extraction and transformation efficiency of cotton protoplasts. In the present study, a cotton callus protoplast extraction method was tested to optimize the ratio of enzymes (cellulase, pectinase, macerozyme R-10, and hemicellulase) used in the procedure. The optimized ratio significantly increased the quantity and activity of protoplasts extracted. We showed that when enzyme concentrations of 1.5% cellulase and 1.5% pectinase, and either 1.5% or 0.5% macerozyme and 0.5% hemicellulase were used, one can obtain increasingly stable protoplasts. We successfully obtained fluorescent protoplasts by transiently expressing fluorescent proteins in the isolated protoplasts. The protoplasts were determined to be suitable for use in further experimental studies. We also studied the influence of plasmid concentration and transformation time on protoplast transformation efficiency. When the plasmid concentration reaches 16 µg and the transformation time is controlled within 12-16 h, the best transformation efficiency can be obtained. In summary, this study presents efficient extraction and transformation techniques for cotton protoplasts.

Global, Regional, and National Burden of Protein-Energy Malnutrition: A Systematic Analysis for the Global Burden of Disease Study.

BACKGROUND: Statistical data on the prevalence, mortality, and disability-adjusted life years (DALYs) of protein-energy malnutrition are valuable for health resource planning and policy-making. We aimed to estimate protein-energy malnutrition burdens worldwide according to gender, age, and sociodemographic index (SDI) between 1990 and 2019. METHODS: Detailed data on protein-energy malnutrition from 1990 to 2019 was extracted from the Global Burden of Disease (GBD) database. The global prevalence, deaths, and DALYs attributable to protein-energy malnutrition and the corresponding age-standardized rates (ASRs) were analyzed. RESULTS: In 2019, the global prevalence of protein-energy malnutrition increased to 14,767,275 cases. The age-standardized prevalence rate (ASPR) showed an increasing trend between 1990 and 2019, while the age-standardized deaths rate (ASDR) and age-standardized DALYs rate presented a significantly decreasing trend in the same period. Meanwhile, there was a clearly ASPR, ASDR, and age-standardized DALYs rate downtrend of the prediction curve when the SDI went up. CONCLUSIONS: PEM still has a relatively serious disease burden in the world, especially in children and the elderly. At the same time, this phenomenon will be more obvious due to the aging of the world's population. Effective prevention measures should be strengthened to continuously improve public health conditions.