EMS Treatment Research Articles

Cryptotanshinone alleviates immunosuppression in endometriosis by targeting MDSCs through JAK2/STAT3 pathway

BackgroundEndometriosis (EMS), a well-recognized chronic inflammatory disorder, characterized by significant immune dysregulation, in which myeloid-derived suppressor cells (MDSCs) are essential for facilitating immunosuppression and driving to disease progression. Cryptotanshinone (CTS) is an active compound capable of modulating MDSC-mediated immunosuppression; however, its therapeutic effects and mechanisms in the treatment of EMS remain unclear. PurposeThis study aims to investigate the therapeutic potential of CTS in modulating MDSCs through JAK2/STAT3 signaling pathway and to evaluate its effects on immune microenvironment and endometriotic lesion growth in EMS. MethodsTranscriptomic data (GSE141549) and single-cell RNA sequencing data (GSE213216) were analyzed to compare immune cell populations in control endometrium (CE), eutopic endometrium (EuE) and ectopic endometrium (EcE) of patients with EMS. Network pharmacology analysis, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) were utilized to explore the molecular mechanism of CTS's effects on MDSCs. A C57BL/6J EMS mice model was established to evaluate CTS's influence on MDSC-mediated immune response in vivo. Flow cytometry and immunofluorescence were used to analyze the immune cell populations, particularly MDSCs and CD8+ T cells. Ex vivo bone marrow (BM)-derived MDSCs were prepared to investigate the modulatory activities of CTS on the frequency and function of MDSCs. The impacts of CTS on JAK2/STAT3 pathway were further examined by western blot. ResultsBioinformatic analysis revealed that, among the three progression stages (CE, EuE, and EcE), the EcE stage exhibited a relatively elevated level of MDSCs and a reduced level of CD8+ T cells. Network pharmacological analysis, along with SPR and CETSA identified that CTS potentially modulates MDSCs in EMS by targeting the JAK2/STAT3 pathway. In vivo studies demonstrated that a relatively high dose of CTS treatment (60mg/kg) effectively inhibited lesion growth, reduced the population of MDSCs, and enhanced CD8+ T cell infiltration. Ex vivo experiments showed that CTS decreased the BM-derived MDSC frequency and rescued the suppressive ability of MDSC upon CD8+ T cells in a dose-dependent manner. Further mechanism analysis confirmed that CTS modulates the expression of immunosuppressive genes and proteins associated with MDSCs through JAK2/STAT3 pathway. ConclusionThis study is the first to demonstrate that CTS is a promising natural compound for EMS treatment by inhibiting MDSC accumulation and modulating MDSC-mediated immune responses. Its therapeutic efficacy is linked to the modulation of the JAK2/STAT3 signaling pathway.

Partial unidirectional translocation from 5AL to 7BS leads to dense spike in an EMS-induced wheat mutant

BackgroundAs the inflorescence of wheat, spike architecture largely determines grain productivity. Dissecting the genetic basis for the spike morphology of wheat can contribute to the designation of ideal spike morphology to improve grain production.ResultsThe present study characterizes a dense spike1 (ds1) mutant, derived from Nongda3753, induced by EMS treatment, which exhibits a dense spike and reduced plant height. Through bulked segregant analysis sequencing (BSA-Seq) of two segregating populations, ds1 was mapped to the short arm of chromosome 7B. Further genotypic and phenotypic analyses of the residual heterozygous lines from F3 to F6 of Yong3002×ds1 revealed that there was a 0-135 Mb deletion in chromosome 7B associated with the dense spike phenotype. The reads count analysis of the two bulks in BSA-Seq, along with the cytological analysis of ds1, ND3753, NIL-ds1 and NIL-Y3002, confirmed that the partial unidirectional translocation of 5AL (543–713 Mb) to 7BS (0-135 Mb) exists in ds1. This translocation led to an increase in both copy number and expression of the Q gene, which is one of the reasons for the dense spike phenotype observed in ds1.ConclusionPartial unidirectional translocation from 5AL to 7BS was identified in the EMS-induced mutant ds1, which exhibits dense spike phenotype. This research illustrates the effect of one chromosome structure variation on wheat spike morphology, and provides new materials with several chromosome structure variations for future wheat breeding.

Enhancing physico-chemical water quality in recycled dairy effluent through microbial consortium treatment

The dairy industry, notorious by generating wastewater rich in organic and nitrogenous content, necessitates sustainable recycling solutions. Biological treatment emerges as a cost-effective and chemical-free alternative. This study delves into the potential of microbial consortium, a microbial consortium, for recycling dairy effluent, aiming at water reclamation and environmental sustainability. Effluent samples from Madurai's Dairy Industry underwent microbial consortium treatment in a recycling prototype, with treatment efficacy assessed through physicochemical parameters and contaminant removal efficiency.Guided by a biodegradability index of 4.51, the study showcased EM's impact, revealing a notable decrease in pH levels, fostering an alkaline environment (2.35 ± 0.06 ppt). Dissolved oxygen increased significantly to 4.50 ppm, indicating improved aerobic conditions. EM treatment led to substantial reductions in calcium (53 %), magnesium (95 %), nitrogen (22 %), sulfate (79 %), phosphate (86 %), BOD (78 %), and COD (82 %). In contrast, dairy effluent treated without microbial consortium during the sludge activation process exhibited negligible water quality improvement.These findings underscore microbial consortium efficacy in advancing biological treatment of dairy effluent, demonstrating a significant reduction in contaminants and showcasing its potential for sustainable water reclamation. Improved alkalinity, dissolved oxygen, and nutrient content further signify positive impacts on ecosystem health. Microbial consortium emerges as a promising avenue for recycling dairy effluent, offering an economically viable and environmentally friendly solution. The study emphasizes the crucial role of microbial treatments in achieving efficient water reclamation, contributing to a cleaner and sustainable environment. Future research and broader implementation of microbial consortium in dairy industry wastewater management are recommended for enhanced environmental benefits.

The mechanism of wen jing tang in the treatment of endometriosis: Insights from network pharmacology and experimental validation

BackgroundEndometriosis (EM) is a hormone-dependent condition marked by progressively severe secondary dysmenorrhea, significantly impacting patients' quality of life and overall health. Wen Jing Tang (WJT), a traditional Chinese medicinal formulation derived from the Synopsis of the Golden Chamber, has proven to be an effective therapeutic agent for EM. However, the precise molecular mechanisms underlying its efficacy remain unclear. ObjectiveThis study aims to elucidate the underlying mechanisms of WJT in the treatment of EM by integrating network pharmacology analysis with experimental validation. MethodsThe chemical constituents and target sites of WJT were obtained from the TCMSP database, while EM-related target genes were sourced from OMIM, TTD, GeneCards, and the DrugBank databases. A "herbs-components-targets" network was constructed using Cytoscape 3.9.1. The intersecting target genes of WJT and EM were then uploaded to the STRING database for protein-protein interaction (PPI) analysis. Subsequently, the common target genes were subjected to GO and KEGG enrichment analysis via the DAVID database. Molecular docking were employed to analyze the binding affinities between the top five core components and their respective targets. Additionally, ELISA were used to quantify the serum levels of IL-6, IL-1β, E2, and P in EM model rats. The expression levels of TNF-α, HIF1A, STAT3, and EGFR mRNA and proteins in ectopic endometrial tissue were assessed using q-PCR and Western blotting. ResultsA total of 250 chemical components and 553 targets were identified in WJT, while 3491 EM-related targets were screened from multiple databases. Among these, 187 common targets between WJT and EM were found, with quercetin, kaempferol, and beta-sitosterol emerging as the core chemical components, and AKT1, IL6, TNF, and IL1B identified as the key targets. These core components demonstrated strong binding affinities to the targets. GO and KEGG enrichment analyses revealed that the shared targets were primarily involved in the HIF1 signaling pathway. Furthermore, compared to the control group, the EM model rats exhibited an increased ectopic endometrial area, disordered glandular and stromal cells, and notable inflammatory infiltration. Serum levels of IL-6, IL-1β, E2, and P were significantly elevated (P < 0.01), and the expression of TNF-α, HIF1A, STAT3, and EGFR in the ectopic endometrium was markedly increased (P < 0.01). Following WJT intervention, the ectopic endometrial area in model rats was reduced, the morphology and structure of the endometrial cells showed improvement, and serum levels of IL-6, IL-1β, E2, and P were significantly decreased (P < 0.05). WJT also inhibited the expression of HIF1 pathway-related proteins TNF-α, HIF1A, STAT3, and EGFR (P < 0.05). ConclusionThe mechanism by which WJT prevents and treats EM may involve the reduction of inflammation through the inhibition of the HIF1 signaling pathway.

Morphological and genetic characterization of mutants of Gladiolus cultivar prince of orange for two successive vegetative generations

Gladiolus mutants developed using gamma irradiations and EMS treatments were characterized using morphological, genetic and Polymerase Chain Reactions (PCR) based Inter-Simple Sequence Repeats (ISSR) for designing future breeding strategies. As many as 7 mutants based on phenotypic variations such as colour and shape modifications were subjected to molecular characterization using 11 ISSR primers that confirmed variations. ISSR markers showed 13.88 to 36.00 percent polymorphism among the mutants was recorded, signifying variability among different mutants. UPGMA (unweighted pair group method with arithmetic mean) based analysis of cluster separated gladiolus variety prince of orange mutants into four clusters. ISSR markers were subjected for comparative analysis like effective multiplex ratio, marker index, polymorphic information content and resolving power wherein, highest EMR (3.24), MI (1.32) were found for UBC 810, Rp (4.37) values were found for UBC 827, and maximum PIC value (0.46) for ISSR 22218 UBC 812. The results clearly indicated the reproducibility of ISSRs and their ability to detect variability among the mutants. A significant level of genetic variation was depicted by ANOVA which suggested the usefulness of studies in gladiolus breeding and unique bands obtained could be utilized for mutant/ varietal identification.

Identification of Drought Tolerant Fenugreek Mutants at Seedling Stage Through Multi-Trait Genotype-Ideotype Distance Index (MGIDI)

The top-performing mutants from the M2 generation, induced by a combination of γ radiation and EMS treatment, underwent screening for drought tolerance at the seedling stage in the M3 generation under controlled laboratory conditions. This investigation aimed to assess their potential for drought tolerance. The top 15 high-yielding mutants were assessed under both normal (control) and induced drought conditions (10% PEG solution). Utilizing the MGIDI method, the evaluation provided valuable insights into selection traits and identified mutants with potential drought tolerance. Under normal conditions, mutants M3-181 and M3-149 exhibited superior performance in seedling growth traits, with M3-149 being the top performer under induced drought conditions, followed by M3-181. Their proximity to the red-cutline suggests promising potential that warrants further investigation. Furthermore, these findings indicate that mutant lines displayed superior multi-trait performance compared to the parent cultivar. Specifically, mutants M3-181, M3-149, and M3-29 ranked higher than the parent cultivar under normal conditions, while mutants M3-149, M3-181, and M3-168 surpassed the parent cultivar RMt-1 under induced drought conditions. This underscores the effectiveness of mutation breeding, particularly through the induction of mutations using γ radiation and EMS, as an efficient strategy not only for generating genetic diversity but also for producing variants superior to the parent cultivar. To the best of our knowledge, this is first report made on mutant selection in fenugreek for drought tolerance at seedling stage, using the MGIDI approach.

Dynamic transcriptome profiling revealed a key gene ZmJMJ20 and pathways associated with cadmium stress in maize

Cadmium (Cd) pollution in soil poses a global concern due to its serious impacts on human health and ecological security. In plants, tremendous efforts have been made to identify some key genes and pathways in Cd stress responses. However, studies on the roles of epigenetic factors in response to Cd stress were still limited. In the study, we first gain insight into the gene expression dynamics for maize seedlings under 0 h, 12 h, and 72 h Cd stress. As a result, six distinct groups of genes were identified by hierarchical clustering and principal component analysis. The key pathways associated with 12 h Cd stress were protein modifications including protein ubiquitination, signal transduction by protein phosphorylation, and histone modification. Whereas, under 72 h stress, main pathways were involved in biological processes including phenylalanine metabolism, response to oxygen-containing compounds and metal ions. Then to be noted, one of the most highly expressed genes at 12 h under Cd treatment is annotated as histone demethylases (ZmJMJ20). The evolutionary tree analysis and domain analysis showed that ZmJMJ20 belonged to the JmjC-only subfamily of the Jumonji-C (JmjC) family, and ZmJMJ20 was conserved in rice and Arabidopsis. After 72 h of Cd treatment, the zmjmj20 mutant created by EMS treatment manifested less severe chlorosis/leaf yellowing symptoms compared with wild-type plants, and there was no significant difference in Fv/Fm and φPSII value before and after Cd treatment. Moreover, the expression levels of several photosynthesis-related down-regulated genes in EMS mutant plants were dramatically increased compared with those in wild-type plants at 12 h under Cd treatment. Our results suggested that ZmJMJ20 plays an important role in the Cd tolerance response pathway and will facilitate the development of cultivars with improved Cd stress tolerance.

Frequency and spectrum of viable mutations in mungbean (Vigna radiata (L.) Wilczek)

The mutagenic effect of gamma rays (200Gy, 300Gy, 400Gy, 500Gy, and 600 Gy), ethyl methane sulphonate (0.2%, 0.3%, 0.4%, 0.5%, and 0.6%) and sodium azide (1 mM, 2 mM and 3 mM) on frequency and spectrum of viable mutations in two mungbean varieties viz., WGG-42 and LGG-460 were investigated. A wide spectrum of viable mutations for stature, leaf, flowering/maturity duration, cotyledonary leaf, pod, seed size, seed color, and colour stem were identified in the M2 generation. The spectrum of viable mutants includeda total of 94 mutants in gamma gamma-irradiated population, 132 mutants in EMS and 45 mutants in SA treatments in WGG-42. In LGG-460, a total of 91 mutants in gamma gamma-irradiated population, 118 mutants in EMS treated population, and 45 mutants in SA treatments were observed. Viable mutation frequency increased with an increase in dose/concentration of gamma rays, EMS, and SA treatments in both genotypes. In both the genotypes, EMS showed the highest frequency of viable mutations than gamma rays and SA treatments. These viable mutants could be exploited as a variety or donor for bringing desirable traits into the otherwise well-adapted cultivars.

Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines.

Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study's aim was to assess the current status of states' OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States. Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher's exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols. Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%). There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.

EMS Treatment Guidelines in Major Traumatic Brain Injury With Positive Pressure Ventilation.

The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown. To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV. The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and included participants who received prehospital PPV. Outcomes were compared between the preimplementation and postimplementation cohorts using logistic regression, stratified by predetermined TBI severity categories (moderate, severe, or critical). Data were collected from January 2007 to June 2017, and data were analyzed from January to February 2023. Implementation of the evidence-based guidelines for the prehospital care of patient with TBI. The primary outcome was survival to hospital discharge, and the secondary outcome was survival to admission. Among the 21 852 participants in the main study, 5022 received prehospital PPV (preimplementation, 3531 participants; postimplementation, 1491 participants). Of 5022 included participants, 3720 (74.1%) were male, and the median (IQR) age was 36 (22-54) years. Across all severities combined, survival to admission improved (adjusted odds ratio [aOR], 1.59; 95% CI, 1.28-1.97), while survival to discharge did not (aOR, 0.94; 95% CI, 0.78-1.13). Within the cohort with severe TBI but not in the moderate or critical subgroups, survival to hospital admission increased (aOR, 6.44; 95% CI, 2.39-22.00), as did survival to discharge (aOR, 3.52; 95% CI, 1.96-6.34). Among patients with severe TBI who received active airway interventions in the field, guideline implementation was independently associated with improved survival to hospital admission and discharge. This was true whether they received basic airway interventions or advanced airways. These findings support the current guideline recommendations for aggressive prevention/correction of hypoxia and hyperventilation in patients with severe TBI, regardless of which airway type is used.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study

BackgroundEndometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. ObjectiveTo characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. MethodsWe retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). ResultsUsing a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. ConclusionWhen controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

Therapeutic effects of Huayu Jiedu formula on endometriosis via downregulating GATA 6 expression

BackgroundEndometriosis (EMs) is a common chronic inflammatory disease which is characterized by multiple clinical symptoms and high recurrence rate due to the absence of effective therapies. Huayu Jiedu Formula (HYJDF), is a traditional Chinese medicine prescription with five major herbs. It has been used as traditional medicine to treat EMs for more than twenty years and exerted a good therapeutic effect. However, the underlying mechanism is unclear. Here we aim to observe the effects of HYJDF on EMs and investigate the therapeutic mechanism. MethodsThe extract components of HYJDF were identified and quantified by an UHPLC-QE-MS method. Network pharmacology was used to obtain the core targets of HYJDF for the treatment of EMs and the specific biologic processes involved. A total of 68 EMs cases were randomly divided into control (gestrinone) and observation (HYJDF) groups. The overall effectiveness, pain scores, cyst-size changes, serum CA125 levels, quality-of-life scores, safety, and adverse events were evaluated before and after treatment. For the mechanism research, DNA methylation-chip analysis was performed to determine the differential genes. EMs mice models and human ectopic stromal cells (ESCs) were treated with HYJDF and its pharmaceutical serum, respectively. The ectopic foci was measured via H&E staining while the expressions of the target genes were verified by real-time PCR and Western blot analysis. The inflammatory cytokine levels in the peritoneal fluid of mice were detected by ELISA. The proliferative potential of cells was analyzed by MTS whereas the apoptosis and cell cycle were determined through flow analysis. ResultsThe total number of components detected in positive and negative ion modes was 839 and 597, respectively. Network pharmacology suggested that HYJDF treated EMs through DNA methylation. We found that HYJDF and gestrinone exerted good therapeutic effect with no obvious difference, but the HYJDF treatment group had fewer side effects. GATA 6, which was hypomethylated and abundant in endometriotic cells, potently induced inflammatory response. This finding indicated the important role of GATA 6 in EMs development. Moreover, HYJDF ameliorated inflammatory response (i.e., reduced the levels of IL-1β and PGE2 in peritoneal fluid), suppressed ESCs proliferation, and increased cell apoptosis by down-regulating GATA 6 expression. ConclusionWe demonstrated that HYJDF has anti-inflammation activity and increased cell apoptosis through the reduction of GATA 6 expression in ectopic tissues, which showed good therapeutic effect without any obvious side effects. These findings suggest that HYJDF may be a new and efficient traditional Chinese medicine for the treatment of EMs.

Development and phenotypic screening of gamma rays and ethyl methanesulphonate mutant populations in tartary buckwheat (Fagopyrum tartaricum (L.) Gaertn)

Tartary buckwheat (F. tartaricum) is an annual self-pollinated pseudo-cereal crop of the Polygonaceae family which is grown worldwide for its nutritive and medicinal value. In order to increase genetic variability and develop genetic resources for crop improvement, gamma rays and EMS were used to develop mutagenized populations in F. tartaricum. In the present study, the biological effect of different doses and concentration of gamma rays and EMS on F. tartaricum to assess the sensitivity of mutagens to create genetic variability was determined. The results revealed that 219.15 Gy of gamma rays and 0.49 % of EMS were optimum for conducting mutagenesis in buckwheat. Both mutagens showed significant effects on the growth parameters in M1 generation. The mutagenic treatments were efficient in creating numerous types of chlorophyll mutations in M2 generation. The frequency of chlorophyll mutation was 1.67 % and 2.70 % for gamma rays and EMS, respectively. These findings shows that EMS is more efficient and effective at inducing variation than gamma rays. A diverse range of morphological mutants affecting every growth stage were screened with the highest frequency in 150 Gy gamma rays and 0.3 % of EMS treatment. . Six morphological mutant types influencing plant height, leaf morphology, growth habit, days to flowering, maturity period, seed yield and seed morphology emerged from induced phenotypic changes in individual plants of the M2 population were identified and selected. This study demonstrated the effectiveness of gamma rays and EMS in increasing genetic diversity and the successful execution of induced mutagenesis in the buckwheat. These mutants may be a valuable source of many beneficial genes in hybridization programs. It is anticipated that both these populations will be a valuable resource for functional genomics research in buckwheat.

Unraveling immunotherapeutic targets for endometriosis: a transcriptomic and single-cell analysis.

Endometriosis (EMs), a common gynecological disorder, adversely affects the quality of life of females. The pathogenesis of EMs has not been elucidated and the diagnostic methods for EMs have limitations. This study aimed to identify potential molecular biomarkers for the diagnosis and treatment ofEMs. Differential gene expression (DEG) and functional enrichment analyses were performed using the R language. WGCNA, Random Forest, SVM-REF and LASSO methods were used to identify core immune genes. The CIBERSORT algorithm was then used to analyse the differences in immune cell infiltration and to explore the correlation between immune cells and core genes. In addition, the extent of immune cell infiltration and the expression of immune core genes were investigated using single-cell RNA (scRNA) sequencing data. Finally, we performed molecular docking of three core genes with dienogest and goserelin to screen for potential drug targets. DEGs enriched in immune response, angiogenesis and estrogen processes. CXCL12, ROBO3 and SCG2 were identified as core immune genes. RT-PCR confirmed that the expression of CXCL12 and SCG2 was significantly upregulated in 12Z cells compared to hESCs cells. ROC curves showed high diagnostic value for these genes. Abnormal immune cell distribution, particularly increased macrophages, was observed in endometriosis. CXCL12, ROBO3 and SCG2 correlated with immune cell levels. Molecular docking suggested their potential as drug targets. This study investigated the correlation between EMs and the immune system and identified potential immune-related biomarkers. These findings provided valuable insights for developing clinically relevant diagnostic and therapeutic strategies for EMs.

Therapeutic targets for endometriosis: Genome-wide Mendelian randomization and colocalization analyses

BackgroundEndometriosis (EM) greatly affects women's reproductive health, identifying new drug targets for EM is urgently needed. This study utilizes comprehensive genome-wide Mendelian randomization (MR) and colocalization analyses, using genomic data, to identify potential therapeutic approaches for EM. MethodsGenome-wide cis-expression quantitative trait loci (cis-eQTL) data were obtained from GTEx V8, which included 838 participants across 49 tissues or cells, and the eQTLGen consortium, which included 31,684 participants. Genome-wide association analysis (GWAS) data for EM were sourced from the FinnGen study, which consisted of 8,288 cases and 68,969 controls, as well as the UK Biobank study, which included 1,496 cases and 359,698 controls. This study utilized MR analysis to assess the correlation between genes and the risk of EM. Subsequently, colocalization analysis was conducted to investigate potential shared causal variants between the identified genes and EM. ResultsAfter conducting MR and colocalization analyses, we identified a total of 13 genes that showed significant evidence of colocalization. These genes are considered promising therapeutic candidates for treating EM. Among them, inner membrane mitochondrial protein (IMMT), src kinase associated phosphoprotein 1 (SKAP1), lysine methyltransferase 5A (KMT5A), KLF transcription factor 12 (KLF12), GRB10 interacting GYF protein 1 (GIGYF1), Wnt family member 7A (WNT7A), Sad1 and UNC84 domain containing 1 (SUN1), and poly (ADP-ribose) polymerase family member 3 (PARP3) were found to have positive associations with the risk of EM. On the other hand, progestin and adipoQ receptor family member 8 (PAQR8), adaptor related protein complex 3 subunit mu 1 (AP3M1), surfeit 6 (SURF6), TUB bipartite transcription factor (TUB), and DNA polymerase delta interacting protein 2 (POLDIP2) were found to have inverse relationships with the risk of EM. ConclusionsThrough genome-wide MR studies, a comprehensive set of genes associated with EM has been identified. Among them, IMMT, PAQR8, SKAP1, KMT5A, AP3M1, SURF6, KLF12, GIGYF1, TUB, WNT7A, SUN1, POLDIP2, and PARP3 show potential as therapeutic targets for EM treatment. Nonetheless, it is crucial to conduct further rigorous investigations to validate these prospects.

Effects of Alkaline Hydrogen Peroxide and Cellulase Modifications on the Physicochemical and Functional Properties of Forsythia suspensa Dietary Fiber.

Besides active substances, Forsythia suspensa is rich in dietary fiber (DF), but it is often wasted or discarded and not put to good use. In order to improve the function of Forsythia DF, it was modified using alkaline hydrogen peroxide (AHP) and cellulase (EM). Compared to the control DF (ODF), the DF modified using AHP (AHDF) and EM (EMDF) had a looser microstructure, lower crystallinity, and higher oil holding capacity (OHC) and cation exchange capacity (CEC). The AHP treatment significantly increased the water holding capacity (WHC) and water swelling ability (WSA) of the DF, while the EM treatment achieved just the opposite. Moreover, the functional properties of AHDF and EMDF, including their cholesterol adsorption capacity (CAC), nitrite ion adsorption capacity (NAC), glucose adsorption capacity (GAC), glucose dialysis retardation index (GDRI), α-amylase inhibitory activity, and DPPH radical scavenging activity, were far better than those of ODF. Together, the results revealed that AHP and EM modifications could effectively improve or enhance the physicochemical and functional properties of Forsythia suspensa DF.

Construction of Watermelon Mutant Library Based on 60Co γ-ray Irradiation and EMS Treatment for Germplasm Innovation

Watermelon is a crucial horticultural crop worldwide but its genetic base has become extremely narrow owing to long-term cultivation. Induced mutagenesis can create a range of variations with distinctive agricultural characteristics. To broaden the genetic diversity of watermelon, we established a mutagenesis library containing over 4000 M1 seeds from an inbred line ‘M08’, which was irradiated by 350 Gy of 60Co γ-rays for 3 h. The rates of germination, emergence, and survival of the M1 seeds were reduced by 5.88%, 18.66%, and 41.96%, respectively. After phenotypic screening, 20 and 10 types of morphological changes were observed in the M1 and M2 generations, with approximately 10.57% and 14.17% mutation frequencies, respectively. Six mutants with desirable horticultural alterations were selected for additional presentation, including the leaf color mutant C1-NO.1, the yellow peel mutant C1-NO.2, the pericarp thickening mutant C1-NO.3, the pericarp thinning mutant C1-NO.4, the seedless mutant C1-NO.5, and the C2-No.1 mutant with normal female flowers and malformed male flowers. Moreover, the three mutants M1-3, M2-1, and M1-5 were identified from our EMS-induced M2 library, exhibiting the fusiform fruit, the dark green peel, and the yellow leaves, respectively. Compared to the wild type (WT), the photosynthetic pigments and parameters were negatively impacted in the yellow-leaf mutant M1-5. For example, the total chlorophyll was 1.22 and 2.22 mg/g in the young and mature leaves of M1-5, respectively, which were significantly lower than those in the WT (2.58 and 2.90 mg/g, respectively). Notably, some mutagenesis phenotypes could be stably inherited, including traits such as yellow leaf color, fusiform fruit shape, and thickening and thinning pericarp. Taken together, these results indicate that these two mutant libraries serve as essential resources to discover new phenotypic germplasms, thereby facilitating the genetic breeding and functional gene exploration in watermelon.

In-vitro Screening of EMS and Sodium Azide Induced Mutant Population at Seedling Stage for Drought Tolerance in Wheat (Triticum aestivum L.)

Drought caused by climate change result in water shortages, decreased global wheat production and unevenly distributed heavy rains. About 50% of the global wheat production is affected by water deficit conditions. The effects of different concentrations of EMS and SA on HD-3226 and HI-1620 wheat genotype for drought tolerance capability were investigated at seedling stage under water and osmotic stress conditions. In the present study, 15% concentration of polyethylene glycol (PEG-6000, to mimic drought stress) was used for in-vitro screening of EMS and SA induced mutant lines of both wheat genotypes. Current study revealed that SA decreased germination of seeds, seedling length, seed vigour index and survival rate percentage while it increased morphological mutation frequency percentage as comparison to EMS treatment in both wheat genotypes under water and PEG stress. Moreover, osmotic stress significantly reduced seed germination, shoot length, root length, seed vigour index, survival rate percentage compared to control-wild type.

Improving desirable agronomic traits of M2 lines on fourteen Ethiopian Sesame (Sesamum indicum L.) genotypes using Ethyl Methane Sulphonate (EMS).

Sesame is an important oilseed crop cultivated in Ethiopia as a cash crop for small holder farmers. However, low yield is one of the main constraints of its cultivation. Boosting and sustaining production of sesame is thus timely to achieve the global oil demand. This study was, therefore, aimed at identifying mutant genotypes targeted to produce better agronomic traits of M2 lines on fourteen Ethiopian sesame genotypes through seed treatment with chemical mutagens. EMS was used as a chemical mutagen to treat the fourteen sesame genotypes. Quantitative and qualitative data were recorded and analyzed using analysis of variance with GenStat 16 software. Post-ANOVA mean comparisons were made using Duncan's Multiple Range Test (p≤ 0.01). Statistically significant phenotypic changes were observed in both quantitative and qualitative agronomic traits of the M2 lines. All mutant genotypes generated by EMS treatment showed a highly significant variation for the measured quantitative traits, except for the traits LBL and LTL. On the other hand, EMS-treated genotypes showed a significant change for the qualitative traits, except for PGT, BP, SSCS, LC, LH and LA traits. Mutated Baha Necho, Setit 3, and Zeri Tesfay showed the most promising changes in desirable agronomic traits. To the best of our knowledge, this study represents the first report on the treatment of sesame seeds with EMS to generate desirable agronomic traits in Ethiopian sesame genotypes. These findings would deliver an insight into the genetic characteristics and variability of important sesame agronomic traits. Besides, the findings set up a foundation for future genomic studies in sesame agronomic traits, which would serve as genetic resources for sesame improvement.

Effectiveness of repeated mutagenesis of sesame crosses for enhancing polygenic variability in F2M2 generation.

The value of combining hybridization and mutagenesis in sesame was examined to determine if treating hybrid sesame plant material with mutagens generated greater genetic variability in four key productivity traits than either the separate hybridization or mutation of plant material. In a randomized block design with three replications, six F2M2 varieties, three F2varieties, and three parental varieties were assessed at Odisha University of Agriculture and Technology, Bhubaneswar, Odisha, India. The plant characteristics height, number of seed capsules per plant, and seed yield per plant had greater variability in the F2M2 generation than their respective controls (F2), however, the number of primary branches per plant varied less than in the control population. The chances for trait selection to be operative were high for all the characteristics examined except the number of primary branches per plant, as indicated by heritability estimates. Increases in the mean and variability of the characteristics examined indicted a greater incidence of beneficial mutations and the breakdown of undesirable linkages with increased recombination. At both phenotypic and genotypic levels strong positive correlations between both primary branch number and capsule number with seed yield suggest that these traits are important for indirect improvement in sesame seed yield. As a result of the association analysis, sesame seed yield and its component traits improved significantly, which may be attributed to the independent polygenic mutations and enlarged recombination of the polygenes controlling the examined characteristics. Compared to the corresponding control treatment or to one cycle of mutagenic treatment, two cycles of mutagenic treatment resulted in increased variability, higher transgressive segregates, PTS mean and average transgression for sesame seed yield. These findings highlight the value of implementing two EMS treatment cycles to generate improved sesame lines. Furthermore, the extra variability created through hybridization may have potential in subsequent breeding research and improved seed yield segregants may be further advanced to develop ever-superior sesame varieties.