Mutations In Gene Research Articles

An intranasal attenuated Coxsackievirus B3 vaccine induces strong systemic and mucosal immunity against CVB3 lethal challenge.

Coxsackievirus B3 (CVB3) triggers viral myocarditis, with no effective vaccine yet. This fecal-oral transmitted pathogen has prompted interest in mucosal immunization strategies to impede CVB3 spread. We developed a new attenuated vaccine strain, named CVB3(mu). The potential of CVB3(mu) to stimulate mucosal immune protection remains to be elucidated. This study evaluates the attenuation characteristics of CVB3(mu) via a rapid evolution cellular model and RNA sequencing. Its temperature sensitivity and safety were evaluated through in vitro and in vivo experiments. The mucosal immunity protection of CVB3(mu) was assessed via intranasal immunization in Balb/c mice. The results indicate that CVB3(mu) exhibits temperature sensitivity and forms smaller plaques. It sustains fewer genetic mutations and still possesses certain attenuated traits up to the 25th passage, in comparison to CVB3(WT). Intranasal immunization elicited a significant serum neutralizing antibodies, and a substantial sIgA response in nasal washes. In vivo trials revealed CVB3(mu) protection in adult mice and passive protection in suckling mice against lethal CVB3(WT) challenges. In conclusion, CVB3(mu), a live attenuated intranasal vaccine, provides protection involving humoral and mucosal immunity, making it a promising candidate to control CVB3 spread and infection.

DISSyphilis and the risk of HIV infection: A Mendelian randomization study.

To assess the causal effect of syphilis on HIV infection by Mendelian randomization analysis. The data of syphilis and HIV infection were obtained from genome-wide association studies, Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database. Analysis involved the identification of key molecules and relevant signaling pathways. MR analysis showed a significant causal relationship between syphilis and HIV infection (WM, OR: 1.098, 95%CI: 1.033-1.217, P = 0.003; IVW, OR: 1.095, 95%CI: 1.048-1.145, P < 0.001). We discovered that rs138697742, a genetic variant related to the RPAIN gene, is associated with HIV infection, and influences the expression of RPAIN, possibly contributing to the progression of the disease. Moreover, single-cell data analysis revealed the cellular communication patterns within PLWH, with monocytes appearing to play a crucial role. In summary, our study reveals a direct causal relationship between syphilis and HIV infection. Additionally, the upregulation of RPAIN gene expression resulting from genetic mutations may serve as a key factor in promoting the progression of HIV infection. Targeting the RPAIN/GALECTIN merges as a promising novel therapeutic target for managing HIV infection.

EVALUATION OF THE EFFECTIVENESSE OF ORTOGNATHIC SURGERY IN THE TREATMENT OF FACIAL ASYMMETRY

The beginning of facial development occurs between the fourth and eighth week of gestation, during this period the cells of the neural crest migrate, forming the four pharyngeal arches that will provide the emergence of most of the structures of the head and neck. During this process, failures may occur such as: epithelial disintegration, absence of fusion, genetic mutations, prognatism or retrognatism, among other factors that cause the appearance of asymmetries in the bones of the face and soft tissues. Aiming at this perspective, the buccal-maxillofacial surgical procedures such as: the treatment of cleft lip and palate, the possibility of bone or alloplastic grafting, in regions of deficit or that have suffered some type of facial trauma, and orthognathic surgery, a theme that will be addressed in this article, have emerged as a new possibility of definitive and resolutive treatment, generating aesthetic harmony and quality of life to the treated patients.

Clinical presentation and genetic characterization of early-onset atrial fibrillation in patients affected by long QT syndrome: A single-center experience.

Early-onset atrial fibrillation (AF) has already been observed in approximately 2% of patients with genetically proven long QT syndrome (LQTS). This frequency is higher than population-based estimates of early-onset AF. However, the concomitant expression of AF in LQTS is likely underestimated. The purpose of this study was to examine the clinical presentation, genetic background, and outcomes of a cohort of patients with LQTS and early-onset AF referred to a single tertiary center. Twenty-seven patients diagnosed with congenital LQTS were included in the study based on the documentation of early-onset (age ≤50 years) clinical or subclinical AF episodes in all available medical records, including standard electrocardiograms, wearable monitor or cardiac implantable electronic devices. Seventeen patients experienced clinical AF during the follow-up period. Subclinical AF was detected in 10 patients through insertable or wearable cardiac monitors. In our series, the mean heart rate during AF episodes was found to be relatively low despite the patients' young age and the low or minimal effective doses of beta-blockers used for QTc interval control. All patients exhibiting LQTS and early-onset AF were genotype positive, carrying mutations in the KCNQ1 (66%), KCNH2, KCNE1, and SCN5A genes. Notably, most of these patients carried the same p.(R231C) mutation in the KCNQ1 gene (59%) and were from the same families, suggesting concurrent expression of familial AF and LQTS. LQTS patients are prone to developing clinical and subclinical AF, even at a younger age. The occurrence of early-onset AF in the LQTS population could be more frequent than previously assumed. AF should be considered as a potential dysrhythmia related to LQTS. Our study emphasizes the importance of carefully researching clinical and/or subclinical episodes of AF through strict heart rhythm monitoring in the LQTS population.

Outcome Measures in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder primarily affecting males, caused by mutations in the dystrophin gene. The absence of dystrophin protein leads to progressive skeletal muscle degeneration. Recent advances in the therapeutic landscape underscore the need to identify appropriate outcome measures to assess treatment efficacy in ambulant and non-ambulant DMD patients, across clinical and research settings. This is essential for accurately evaluating new treatments and attributing therapeutic benefits.It is crucial to establish a robust correlation between outcome scores and disease progression patterns. This task is challenging since functional test performance may be influenced by different patient's characteristics, including the physiological evolution of the neurodevelopment together with the disease progression. While widely used DMD outcomes such as the North Star Ambulatory Assessment, the 6-Minute Walking Test, the 4 stairs climbed, and the Performance of the Upper Limb exhibit reliability and validity, their clinical significance is influenced by the wide phenotype and progression variability of the disease.We present and discuss the features (relevance, quantifiability, validity, objectivity, reliability, sensitivity, specificity, precision) of available DMD outcome measures, including new potential measures that may be provided by digital tools and artificial intelligence.

NKX2.5 coding exons sequencing reveals novel non-synonymous mutations in patients with sporadic congenital heart diseases among the Tanzanian population

BackgroundThe evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene.ResultsIn this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects.ConclusionMutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.

Dysregulation of myelination-related genes in schizophrenia.

Schizophrenic individuals display disrupted myelination patterns, altered oligodendrocyte distribution, and abnormal oligodendrocyte morphology. Schizophrenia is linked with dysregulation of a variety of genes involved in oligodendrocyte function and myelin production. Single-nucleotide polymorphisms (SNPs) and rare mutations in myelination-related genes are observed in certain schizophrenic populations, representing potential genetic risk factors. Downregulation of myelination-related RNAs and proteins, particularly in frontal and limbic regions, is consistently associated with the disorder across multiple studies. These findings support the notion that disruptions in myelination may contribute to the cognitive and behavioral impairments experienced in schizophrenia, although further evidence of causation is needed.

Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers

Homologous recombination (HR) is a high-fidelity DNA double-strand break (DSB) repair pathway. Both familial and somatic loss of function mutation(s) in various HR genes predispose to a variety of cancer types, underscoring the importance of error-free repair of DSBs in human physiology. While environmental sources of DSBs have been known, more recent studies have begun to uncover the role of endogenous base damage in leading to these breaks. Base damage repair intermediates often consist of single-strand breaks, which if left unrepaired, can lead to DSBs as the replication fork encounters these lesions. This review summarizes various sources of endogenous base damage and how these lesions are repaired. We highlight how conversion of base repair intermediates, particularly those with 5′or 3′ blocked ends, to DSBs can be a predominant source of genomic instability in HR-deficient cancers. We also discuss how endogenous base damage and ensuing DSBs can be exploited to enhance the efficacy of Poly (ADP-ribose) polymerase inhibitors (PARPi), that are widely used in the clinics for the regimen of HR-deficient cancers.

Fibroblast growth factor homologous factors: canonical and non-canonical mechanisms of action.

Since their discovery nearly 30years ago, fibroblast growth factor homologous factors (FHFs) are now known to control the functionality of excitable tissues through a range of mechanisms. Nervous and cardiac system dysfunctions are caused by loss- or gain-of-function mutations in FHF genes. The best understood 'canonical' targets for FHF action are voltage-gated sodium channels, and recent studies have expanded the repertoire of ways that FHFs modulate sodium channel gating. Additional 'non-canonical' functions of FHFs in excitable and non-excitable cells, including cancer cells, have been reported over the past dozen years. This review summarizes and evaluates reported canonical and non-canonical FHF functions.

Clinical trials of new therapies for mucopolysaccharidoses

Background: Mucopolysaccharidoses (MPS) are a group of rare genetic diseases with a metabolic background. Currently, there are no effective methods of treating MPS, and new ways of treating patients are constantly being sought.Aim of the study: The purpose of this article is to review the available literature on clinical trials of new treatments for mucopolysaccharidoses.Material and methods: The review of research literature published between 1999 and 2023 was conducted, with a specific focus on the last ten years. The literature for this article was selected from publications available online in databases such as Google Scholar or PubMed. Research was based on keywords like: mucopolysaccharidoses, clinical trials, gene therapy, MPS. Results: A total of 104 publications were considered in the study, including 95 scientific articles and 9 clinical trial reports (consisting of 1 FDA approval). Out of those 104 articles, 82 discussed potential future therapies for patients with MPS. Among them, as many as 51 focused on gene therapy.Conclusions: The only currently approved treatments for mucopolysaccharidoses are enzyme replacement therapy and hematopoietic stem cell transplantation, which are not suitable for all types of MPS and have their limitations. In addition, there is no single therapy for all types of MPS, as they are the result of mutations in different genes and result from the deficiency of different enzymes. Numerous preclinical and clinical studies are being conducted on therapies for mucopolysaccharidoses. These include therapies that allow manipulation of cellular pathways, substrate reduction, or gene therapy, which is the most promising form of treatment. Some of the studies have successfully passed the first and second research phases.

Comparative Transcriptomic Insights into the Mechanisms Underlying Maize (Zea mays L.) Embryogenic Callus Differentiation

The regeneration of plant somatic cells is a prerequisite for their biological breeding. Identification of key genes controlling embryogenic callus (EC) differentiation and investigation of the genetic mechanism of cell fate determination are important for improving plant variety. In this study, we used the maize inbred line KN5585 and its gene-edited mutants Zmprx19-1, Zmprx19-2 and Zmprx19-3 as plant materials. Three somatic regeneration-related traits, the embryogenic callus induction rate (EIR), green callus rate (GCR) and plantlet regeneration rate (PRR), were identified by tissue culture of immature embryos. Additionally, the ECs at different differentiation stages (0 d, 5 d, 10 d and 15 d) were subjected to RNA-seq, and comparative transcriptome analyses were performed. The results showed that the somatic regeneration traits of the mutants were all highly significantly lower than those of the wild type (p &lt; 0.01). The PRR value of KN5585 was 75.25%, while the highest PRR of the mutants was only 15.08%, indicating that knockdown of ZmPRX19 inhibited EC regeneration. Transcriptome sequencing yielded a total of 200.30 Gb of clean data from 24 libraries, with an average of 6.53 Gb of clean data per library. Mutant and wild-type gene expression data were compared separately at four differentiation stages, and 689 common differentially expressed genes (DEGs) were screened. WGCNA was used to classify these genes into nine modules, which were subsequently subjected to GO and KEGG enrichment analyses. In total, 40, 23, 17 and 5 genes were significantly (q &lt; 0.05) enriched in plant hormone signal transduction, the MAPK signaling pathway-plant, phenylpropanoid biosynthesis and photosynthesis, respectively. Moreover, protein–protein interaction (PPI) network analysis revealed five MAPKKK17_18 hub nodes involved in the MAPK pathway-plant, which may be the key genes controlling plantlet differentiation from ECs. The above results provide a basis for the final elucidation of the molecular mechanism of plant somatic regeneration.

Phenotypic and genotypic assessment of fluoroquinolones and aminoglycosides resistances in Pseudomonas aeruginosa collected from Minia hospitals, Egypt during COVID-19 pandemic

BackgroundOne of the most prevalent bacteria that cause nosocomial infections is Pseudomonas aeruginosa. Fluoroquinolones (FQ) and aminoglycosides are vital antipseudomonal drugs, but resistance is increasingly prevalent. The study sought to investigate the diverse mechanisms underlying FQ and aminoglycoside resistance in various P. aeruginosa strains particularly during the COVID-19 crisis.MethodsFrom various clinical and environmental samples, 110 P. aeruginosa isolates were identified and their susceptibility to several antibiotic classes was evaluated. Molecular techniques were used to track target gene mutations, the presence of genes encoding for quinolone resistance, modifying enzymes for aminoglycosides and resistance methyltransferase (RMT). Efflux pump role was assessed phenotypically and genotypically. Random amplified polymorphic DNA (RAPD) analysis was used to measure clonal diversity.ResultsQnrS was the most frequently encountered quinolone resistance gene (37.5%) followed by qnrA (31.2%) and qnrD (25%). Among aminoglycoside resistant isolates, 94.1% harbored modifying enzymes genes, while RMT genes were found in 55.9% of isolates. The aac(6')-Ib and rmtB were the most prevalent genes (79.4% and 32.3%, respectively). Most FQ resistant isolates overexpressed mexA (87.5%). RAPD fingerprinting showed 63.2% polymorphism.ConclusionsAminoglycosides and FQ resistance observed in this study was attributed to several mechanisms with the potential for cross-contamination existence so, strict infection control practices are crucial.

Risk factors for secondary bladder cancer following prostate cancer radiotherapy.

This review investigates the complex landscape of secondary bladder cancer (SBC) after radiotherapy for prostate cancer (PCa). External beam radiotherapy (EBRT) poses an increased risk for SBC, while brachytherapy seems to be associated with smaller increased risks for SBC due to its targeted radiation delivery, sparing the surrounding bladder tissue. Secondary cancers in the bladder are the most frequently diagnosed secondary cancers in the PCa patient population treated with radiotherapy. Patient-related factors are pivotal, with age emerging as a dual-edged factor. While advanced age is a recognized risk for bladder cancer, younger PCa patients exhibit higher susceptibility to radiation-induced cancers. Smoking, a well-established bladder cancer risk factor, increases this vulnerability. Studies highlight the synergistic effect of smoking and radiation exposure, amplifying the likelihood of genetic mutations and SBC. The latency period of SBC, which spans years to decades, remains a critical aspect. There is a strong dose-response relationship between radiation exposure and SBC risk, with higher doses consistently being associated with a higher SBC risk. While specific models for therapeutic radiation-induced SBC are lacking, insights from related studies, like the Atomic Bomb survivor research, emphasize the bladder's sensitivity to radiation-induced cancer. Chemotherapy in combination with radiotherapy, although infrequently used in PCa, emerges as a potential risk for bladder cancer. Bladder cancer's complex epidemiology, encompassing risk factors, treatment modalities, and cancer types, provides a comprehensive backdrop. As research refines understanding, we hope that this review contributes to guide clinicians, inform patient care, and shape preventive strategies on SBC.

Family Planning in Genetic Optic Atrophies in Israel, a Case Series and a Discussion of Ethical Considerations.

Patients with genetic optic atrophies must navigate all stages of life with their visual impairment, including the important milestone of family planning. Advances in genetic testing now allows physicians and affected families to consider medical help with the aim of preventing blindness through preconception, preimplantation, and perinatal methods. This case series presents 4 patients with different genetic optic atrophies (Leber hereditary optic neuropathy [LHON], autosomal dominant optic atrophy, Wolfram syndrome, and papillorenal syndrome) who were followed by the Neuro-Ophthalmology Unit at a tertiary medical center between 2010 and 2023 and were of child-bearing age. The aim of this study was to increase understanding in family planning options for patients with optic atrophies, raise awareness of the solutions available, and provide guidance for clinicians to support their patients. Advances in medicine, genetics, and medical technology allow multidisciplinary teams to assist patients in fulfilling their desire for a genetically healthy offspring. Customized solutions can be designed to meet the specific challenges posed by each type of genetic optic atrophy. The solutions proposed in this series are based on genetic testing done in the parents, which then allows to plan medical and genetic intervention individually. The solutions opted for in this series range from the decision to not have another child until PGD (Preimplantation genetic diagnosis). We describe how genetic advancements have made it possible for patients with the 4 most common hereditary optic atrophies to fulfill their wish to have children without visually threatening genetic mutations. We also review the recent literature on the penetrance of optic atrophy in OA-mutation carriers and raise 2 significant ethical considerations: the reduction of a future life to a non-life-threatening impairment and that of public expenditure for non-life-threatening conditions.

Clinical efficacy of macrolide antibiotics in mycoplasma pneumoniae pneumonia carrying a macrolide-resistant mutation in the 23 S rRNA gene in pediatric patients

BackgroundThe global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients.MethodsThe baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay.ResultsFirst, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P < 0.05). There were also no statistical association between the mutation and the duration of fever and hospital length of stay.ConclusionMacrolides can be administered to MPP children carrying a macrolide-resistant mutation. tNGS can be seen as a front-line diagnostic in MPP.

Rod-sparing in a bardet-biedl syndrome patient with mutations in the ARL6 gene.

Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder characterized by pleiotropism that affects multiple organ systems. The primary features of BBS include rod-cone dystrophy, renal anomalies, post axial polydactyly, and neurologic deficits. The clinical picture of BBS is extensively heterogenous, with inter and intra familial patients varying in levels of syndromic manifestations and severity of symptoms. In this study we examined a monocular BBS patient who was compound heterozygous for mutations in the ARL6 (BBS3) gene. The patient reported visual complaints consistent with a clinical picture of cone or cone-rod dystrophy. Fundus imaging showed retinal mottling on color photos and a parafoveal hyperfluorescent ring on short wave autofluorescence (SW-AF). Full field electroretinogram (ffERG) revealed normal scotopic step tracings and diminished amplitudes in the photopic steps. This rod-sparing result was consistent with cone-dystrophy and is the first known case of a rod-sparing ffERG phenotype in a BBS patient with mutations in the ARL6 gene. This contributes to the existing phenotype and may potentially contribute to furthering our understanding of BBS pathophysiology.

Human induced pluripotent stem cells (NIHTVBi029-A and NIHTVBi030-A) generated from two patients with a heterozygous mutation in the CDC42 gene

Induced pluripotent stem cells (iPSCs) were successfully generated from peripheral blood mononuclear cells obtained from two patients with a heterozygous mutation in the CDC42 gene. Both iPSC lines expressed pluripotency markers, differentiated into the three germ layers in vitro, showed normal karyotypes, and retained the disease-causing mutation. Created iPSC lines and their differentiated derivatives may be of interest in the study of the physiology of disease mechanisms and therapy.

A FUNÇÃO DOS CANAIS DE SÓDIO NAV1.7 NA DOR NEUROPÁTICA: GENÉTICA, MECANISMOS MOLECULARES, BIOMARCADORES E PERSPECTIVAS TERAPÊUTICAS

The deepening understanding of the molecular mechanisms underlying neuropathic pain has highlighted the importance of the sodium channel Nav1.7, encoded by the SCN9A gene, as a critical element in regulating neuronal excitability and transmitting action potentials. Nav1.7 is found in nociceptive sensory neurons, playing a vital role in conducting pain signals in the peripheral nervous system. Its activity allows the depolarization of neuronal membranes in response to painful stimuli, facilitating the rapid influx of sodium ions into the cell and generating action potentials that are sent to the brain for pain perception. Mutations in the SCN9A gene are strongly linked to various neuropathic pain conditions. Mutations that increase Nav1.7 activity, such as the p.E1113K variant, intensify the excitability of sensory neurons, leading to conditions such as primary erythromelalgia. In contrast, mutations that reduce Nav1.7 functionality, such as p.I230T, result in lower neuronal excitability, culminating in congenital insensitivity to pain. Advances in neuroimaging and molecular genetics have been fundamental in identifying biomarkers of Nav1.7 dysfunctions. These methods allow the detection of changes in pain processing within the central nervous system, facilitating the identification of specific genetic mutations that contribute to neuropathic conditions. Advanced genetic techniques, such as exome and genome sequencing, enable detailed diagnoses and personalized therapeutic approaches. Promising therapies involve specific inhibitors for Nav1.7, aiming to reduce neuronal hyperexcitability. Additionally, gene therapies, including techniques such as CRISPR-Cas9, have been explored to correct mutations in the SCN9A gene. In conclusion, scientific progress allows for precise diagnoses and personalized treatments, promoting effective management of neuropathic pain.

The Role of BrKS in Leafy Head Formation Was Confirmed by Two Allelic Mutants of Chinese Cabbage (Brassica rapa L. ssp. pekinensis)

Considering that the presence of a leafy head is a key morphological characteristic that determines the yield and quality of Chinese cabbage, identifying the major genes regulating the formation of a leafy head is crucial for variety improvement. A heading-related gene, BrKS, was previously predicted from a non-heading mutant, nhm1, derived from a heading variety, which encodes a key enzyme involved in gibberellin biosynthesis. Here, another mutant, nhm2, was identified from the same EMS-mutagenized population, and the phenotype of nhm2 was consistent with that of nhm1. We crossed mutants nhm1 and nhm2, and their F1 plants exhibited the mutant phenotype, which indicated that their mutant genes were allelic. A single non-synonymous mutation in the fourth exon of BrKS in mutant nhm1 and another single non-synonymous mutation in the tenth exon of BrKS in mutant nhm2. The same gene mutation in mutants nhm1 and nhm2 produced a similar non-heading phenotype, which confirmed the role of BrKS in the leafy head formation of Chinese cabbage. RNA-Seq analysis indicated that a transcription factor gene, BrERF1A, which is associated with leaf development, significantly down-regulated expression in mutant nhm1, and after the mutant was treated with GA3, the expression level of BrERF1A was recovered, which indicated that BrKS might be involved in leafy head formation through regulating the expression level of BrERF1A. Our findings provide important clues for revealing the molecular mechanism of leafy head formation in Chinese cabbage.

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis

BackgroundThe tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. MethodsThis research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients’ responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. ResultsThe prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. ConclusionOur study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.