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Abstract Hearing loss(HL) represents a significant public health concern. This study aimed to determine the association between hearing loss and gout and to elucidate the underlying causative mechanisms. Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) basic databases. Initially, baseline characteristics of individuals with and without gout were compared. A nonlinear relationship between pure tone audiometry (PTA) values and gout prevalence was confirmed through restricted cubic spline (RCS) curve analysis. Subsequently, hearing loss was categorized into different levels based on PTA values, and multiple logistic regression analysis was employed to calculate the impact of varying degrees of hearing loss on the risk of gout. Finally, MR analysis was conducted to further elucidate the causal relationship between hearing loss and gout. A total of 3,258 individuals were included in this study, with a gout prevalence of 3.7%. Significant differences were observed between the gout group and the non-gout group in variables such as age, gender, blood uric acid level, BMI, hypertension, and diabetes. RCS curve analysis revealed a significant nonlinear relationship between PTA values and gout risk, particularly when PTA values exceed a specific threshold, where the curve flattens. Based on different levels of hearing loss derived from PTA values, multiple logistic regression analysis demonstrated that mild and moderate hearing loss significantly increased the risk of gout, remaining statistically significant after adjusting for covariates (odds ratio (OR) = 2.10–3.48, P

Abstract Background Oil palm (Elaeis guineensis Jacq.) is a very important tropical woody oil plant with high commercial and ornamental value. The exocarp of the oil palm fruit is rich in anthocyanosides and proanthocyanidins, which not only give it a bright colour, but also mark the maturity of the fruit. The study of the dynamic change pattern of anthocyanoside content and important anthocyanoside metabolism-related regulatory genes during oil palm ripening is conducive to the improvement of the ornamental value of oil palm and the determination of the optimal harvesting period of the fruits. Methods We analyzed the virescens oil palm (AS) and nigrescens oil palm (AT) at 95 days (AS1, AT1), 125 days (AS2, AT2) and 185 days (AS3, AT3) after pollination were used as experimental materials for determining the changes in the total amount of anthocyanins as well as their metabolomics and transcriptomics studies by using the LC-MS/MS technique and RNA-Seq technique. Result The results showed that the total anthocyanin content decreased significantly from AS1 (119 µg/g) to AS3 (23 µg/g), and from AT1 (1302 µg/g) to AT3 (170 µg/g), indicating a clear decreasing trend during fruit development. Among them, the higher flavonoids in AS and AT included anthocyanins such as peonidin-3-O-rutinoside (H35), pelargonidin-3-O-rutinoside (H21), and cyanidin-3-O-glucoside (H7), as well as condensed tannins such as procyanidin B2 (H47), procyanidin C1 (H49), and procyanidin B3 (H48). Notably, nine genes involved in the anthocyanin biosynthetic pathway exhibited up-regulated expression during the pre-development stage of oil palm fruits, particularly during the AS1 and AT1 periods. These genes include: Chalcone synthase (CHS; LOC105036364); Flavanone 3-hydroxylase (F3H; LOC105054663); Dihydroflavonol 4-reductase (DFR; LOC105040724, LOC105048473); Anthocyanidin synthase (ANS; LOC105035842), UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105039612); Flavonoid 3’,5’-hydroxylase (F3’5’H; LOC105036086, LOC105044124, LOC105045493). In contrast, five genes demonstrated up-regulated expression as the fruits developed, specifically during the AS3 and AT3 periods. These genes include: Chalcone synthase (CHS; LOC105036921, LOC105035716); Chalcone isomerase (CHI; LOC105045978); UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT; LOC105046326); Flavonoid 3’-hydroxylase (F3’H; LOC105036086). Conclusion Most of differentially expressed genes exhibited up-regulation during the early stages of fruit development, which may contribute to the elevated anthocyanin content observed in oil palm fruits of both types during the pre-developmental period. Furthermore, the expression levels of most genes were found to be higher in the AT fruit type compared to the AS fruit type, suggesting that the differential expression of these genes may be a key factor underlying the differences in anthocyanoside production in the exocarp of oil palm fruits from these two fruit types. The findings of this study provide a theoretical foundation for the identification and characterization of genes involved in anthocyanin synthesis in oil palm fruits, as well as the development of novel variations using molecular biology approaches.

Abstract Roses are consistently ranked at the forefront in cut flower production. Increasing demands of market and changing climate conditions have resulted in the need to further improve the diversity and quality of traits. However, frequent hybridization leads to highly heterozygous nature, including the allelic variants. Therefore, the absence of comprehensive genomic information leads to them making it challenging to molecular breeding. Here, two haplotype-resolved chromosome genomes for Rosa chinensis ‘Chilong Hanzhu’ (2n = 14) which is high heterozygous diploid old Chinese rose are generated. An amount of genetic variation (1,605,616 SNPs, 209,575 indels) is identified. 13,971 allelic genes show differential expression patterns between two haplotypes. Importantly, these differences hold valuable insights into regulatory mechanisms of traits. RcMYB114b can influence cyanidin-3-glucoside accumulation and the allelic variation in its promoter leads to differences in promoter activity, which as a factor control petal color. Moreover, gene family expansion may contribute to the abundance of terpenes in floral scents. Additionally, RcANT1, RcDA1, RcAG1 and RcSVP1 genes are involved in regulation of petal number and size under heat stress treatment. This study provides a foundation for molecular breeding to improve important characteristics of roses.

Abstract Rose (Rosa) is a prominent ornamental plant that holds substantial economic and social significance. Roses originating from different regions exhibit intricate phenotypic and genetic characteristics, but the majority of rose genetic resources are poorly characterized. In this study, 192 genotypes of the genus Rosa were examined using 33 phenotypic traits and 10 pairs of SSR markers. Compared to wild species, both old garden and modern roses exhibited a significant level of diversity, with flower color having the highest degree of diversity and style morphology having the lowest degree of diversity. This phenomenon may be attributed to the limited utilization of wild roses due to their simpler ornamental traits and the frequent phenotypic and molecular infiltration between old garden roses and modern roses. Following a inaugural comprehensive evaluation employing principal component analysis, R. chinensis ‘Zihongxiang’, R. hybrida ‘Burgundy Iceberg’, R. hybrida ‘Conrad F. Meyer’, R. rugosa ‘Gaohong’ and R. floribunda ‘Sheherazad’ were selected as core germplasm resources for future breeding. Moreover, three tetraploid roses, namely R. hybrida ‘Midnight Blue’, R. floribunda ‘Sheherazad’, and R. hybrida ‘Couture Rose Tilia’, with significant differences in both phenotypic and molecular profiles were selected and reciprocally intercrossed. Ultimately, two populations were obtained exhibiting significant variation in flower size, annual stem color, stem pickle density, and leaf number. Furthermore, our results indicated that the traits of flower diameter, flower height, petal width, and petal number may potentially be controlled by two major-effect loci. In conclusion, this study provides novel insights into the evolutionary patterns of Rosa germplasm resources. It paves the way for identifying core genotypes that carry distinct ornamental characteristics and possess immense value for breeding novel varieties in the future.

The double flower developmental process is regulated via a complex transcriptional regulatory network. To understand this highly dynamic and complex developmental process of Dianthus spp., we performed a comparative analysis of floral morphology and transcriptome dynamics in simple flowers and double flowers. We found that the primordium of double flowers of ‘X’ was larger in size compared to that of simple flowers of ‘L’ in Dianthus chinensis. RNA-seq and Weighted Gene Co-expression Network Analysis (WGCNA) during flower development, identified stage-specific gene network modules. Expression analysis by RNA-seq indicated that a group of genes related to floral meristem identity, primordia position and polarity were highly expressed in double flowers genotypes compared to simple flowers genotypes, suggesting their roles in double-petal formation. A total of 21 DEGs related to petal number were identified between simple and double flowers. The experiments of in situ hybridization revealed that DcaAP2L, DcaLFY and DcaUFO genes were expressed in the intra-sepal boundary and petal boundary. We proposed a potential transcriptional regulatory network for simple and double flower development. This study provides novel insights into the molecular mechanism underlying double flower formation in Dianthus spp.

Abstract Field‐programmable gate array (FPGA)‐based real‐time simulators are often applied in simulations of active distribution networks (ADNs) because of their parallel architectures and low cost. The overall performance of an FPGA‐based real‐time simulator is mainly determined by its kernel solver, which solves the nodal equation at each simulation time step. With the increasing scale of ADNs, real‐time simulations of fast switching dynamics, along with limited computation hardware, have increased the requirements of the solver in terms of both time and resource consumption. In this study, a highly parallel kernel solver is proposed to improve the simulation efficiency of the FPGA‐based real‐time simulator. The multi‐level parallel design and its implementation, including the parallelism at the system and module and element levels, are presented in detail. A modified IEEE 123‐node system with distributed photovoltaics (PVs) is then simulated using a three‐FPGA‐based real‐time simulator. Simulation results are compared with the commercial simulation tool PSCAD/EMTDC to validate the proposed kernel solver.

Abstract The real‐time simulation of active distribution networks (ADNs) can provide an accurate insight into transient behaviours, but faces challenges in simulation efficiency and flexibility brought by larger system scales and wider time‐scale ranges. This paper presents an asynchronous multi‐rate (AMR) method and design for the real‐time simulation of large‐scale ADNs. In the proposed method, the entire ADN was decoupled into different subsystems according to accuracy requirements, and optimized time‐steps were allocated to each subsystem to realize a fully distributed simulation. This not only alleviated the time‐step coordination problem existing in multi‐rate real‐time simulations, but also enhanced the flexible expansion capabilities of the real‐time simulator. To realize the AMR real‐time simulation, a multi‐rate interfacing method, synchronization mechanism, and data communication strategy are proposed in this paper, and their hardware design is also presented in detail. A modified IEEE 123‐node system with photovoltaics and wind turbine generators was simulated on a 3 field‐programmable gate arrays (FPGAs)‐based AMR real‐time simulator. The real‐time results were captured by the oscilloscope and verified with PSCAD/EMTDC, which demonstrated the superiority in simulation flexibility and accuracy compared with the synchronous multi‐rate (SMR) method.

The SEPALLATA (SEP) gene, as a 'glue' for the 'floral quartets model', plays an important role in floral organ development by forming tetramers with class A-, B-, and C- genes. The functional differentiation of class E genes has been reported in different species. Carnation (Dianthus spp.) is a world-famous economic flower that has been extensively used in landscaping, but the roles of SEP genes in carnation are unclear. Here, we found that the class E genes of D. chinensis cultivar 'L' showed different expression patterns during floral organ primordium development by transcriptome analysis. Combined with quantitative real-time PCR, its tissue and specific stage expression patterns were also different in different subclades. In addition, a yeast two-hybrid experiment was carried out to explore the interaction patterns of class E genes with other class A-, B-, and C- genes. Only DcSEP3s and DcSEP4s proteins interacted with all three classes of A-, B-, and C- proteins, and interestingly, is that DcSEP3-1 only interacted with the DcAP1 protein of class A, while the DcSEP3-2 protein only interacted with DcFUL1. Transgenic experiments showed that overexpression of DcSEP3-2 genes in Arabidopsis resulted in early flowering, smaller rosettes, dwarfism and abnormal floral organs. The transgenic line overexpressing of DcSEP3-1 only showed an early flowering phenotype. All these results indicated that the two DcSEP3s of class E genes in D. chinensis may undergo sub-functionalization. These findings advance our understanding of the molecular mechanisms of flower development in carnation.

Abstract Background Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. Methods In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. Results The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. Conclusions The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.

IntroductionOil palm is the world's highest yielding oil crop and its palm oil has high nutritional value, making it an oilseed plant with important economic value and application prospects. After picking, oil palm fruits exposed to air will gradually become soft and accelerate the process of fatty acid rancidity, which will not only affect their flavor and nutritional value, but also produce substances harmful to the human body. As a result, studying the dynamic change pattern of free fatty acids and important fatty acid metabolism-related regulatory genes during oil palm fatty acid rancidity can provide a theoretical basis for improving palm oil quality and extending its shelf life.MethodsThe fruit of two shell types of oil palm, Pisifera (MP) and Tenera (MT), were used to study the changes of fruit souring at different times points of postharvesting, combined with LC-MS/MS metabolomics and RNA-seq transcriptomics techniques to analyze the dynamic changes of free fatty acids during fruit rancidity, and to find out the key enzyme genes and proteins in the process of free fatty acid synthesis and degradation according to metabolic pathways.Results and discussionMetabolomic study revealed that there were 9 different types of free fatty acids at 0 hours of postharvest, 12 different types of free fatty acids at 24 hours of postharvest, and 8 different types of free fatty acids at 36 hours of postharvest. Transcriptomic research revealed substantial changes in gene expression between the three harvest phases of MT and MP. Combined metabolomics and transcriptomics analysis results show that the expression of SDR, FATA, FATB and MFP four key enzyme genes and enzyme proteins in the rancidity of free fatty acids are significantly correlated with Palmitic acid, Stearic acid, Myristic acid and Palmitoleic acid in oil palm fruit. In terms of binding gene expression, the expression of FATA gene and MFP protein in MT and MP was consistent, and both were expressed higher in MP. FATB fluctuates unevenly in MT and MP, with the level of expression growing steadily in MT and decreasing in MP before increasing. The amount of SDR gene expression varies in opposite directions in both shell types. The above findings suggest that these four enzyme genes and enzyme proteins may play an important role in regulating fatty acid rancidity and are the key enzyme genes and enzyme proteins that cause differences in fatty acid rancidity between MT and MP and other fruit shell types. Additionally, differential metabolite and differentially expressed genes were present in the three postharvest times of MT and MP fruits, with the difference occurring 24 hours postharvest being the most notable. As a result, 24 hours postharvest revealed the most obvious difference in fatty acid tranquility between MT and MP shell types of oil palm. The results from this study offer a theoretical underpinning for the gene mining of fatty acid rancidity of various oil palm fruit shell types and the enhancement of oilseed palm acid-resistant germplasm cultivation using molecular biology methods.

The arithmetic optimization algorithm (AOA) is a new metaheuristic algorithm inspired by arithmetic operators (addition, subtraction, multiplication, and division) to solve arithmetic problems. The algorithm is characterized by simple principles, fewer parameter settings, and easy implementation, and has been widely used in many fields. However, similar to other meta-heuristic algorithms, AOA suffers from shortcomings, such as slow convergence speed and an easy ability to fall into local optimum. To address the shortcomings of AOA, an improved arithmetic optimization algorithm (IAOA) is proposed. First, dynamic inertia weights are used to improve the algorithm’s exploration and exploitation ability and speed up the algorithm’s convergence speed; second, dynamic mutation probability coefficients and the triangular mutation strategy are introduced to improve the algorithm’s ability to avoid local optimum. In order to verify the effectiveness and practicality of the algorithm in this paper, six benchmark test functions are selected for the optimization search test verification to verify the optimization search ability of IAOA; then, IAOA is used for the parameter optimization of support vector machines to verify the practical ability of IAOA. The experimental results show that IAOA has a strong global search capability, and the optimization-seeking capability is significantly improved, and it shows excellent performance in support vector machine parameter optimization.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITESeq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8+ skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care. [ABSTRACT FROM AUTHOR]