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PURPOSE: To investigate the role of prognostic genes related to cisplatin resistance in ovarian cancer during disease progression. METHOD: The gene expression profile of the NCI-60 cell line was acquired through comprehensive analysis of the GEO database accession GSE116439. We performed a thorough analysis of gene expression differences in samples from seven individuals exposed to cisplatin concentrations of 0 nM compared to seven samples exposed to 15000 nM over a 24-h period. Key genes were initially identified through LASSO regression, followed by their enrichment through differential gene function analysis (GO) and pathway enrichment analysis (KEGG). Subsequently, a prognostic risk model was established for these key genes. The prognostic model's performance was assessed through K-M survival curves and ROC curves. To examine the variance in immune cell infiltration between the high and low-risk groups, CIBERSORTx analysis was employed. Finally, validation of prognostic gene expression in cisplatin-resistant ovarian cancer was carried out using clinical samples, employing RT-qPCR and Western Blot techniques. RESULTS: A total of 132 differential genes were found between cisplatin resistance and control group, and 8 key prognostic genes were selected by analysis, namely VPS13B, PLGRKT, CDKAL1, TBC1D22A, TAP1, PPP3CA, CUX1 and PPP1R15A. The efficacy of the risk assessment model derived from prognostic biomarkers, as indicated by favorable performance on both Kaplan-Meier survival curves and ROC curves. Significant variations in the abundance of Macrophages M1, T cells CD4 memory resting, T cells follicular helper, and T cells gamma delta were observed between the high and low-risk groups. To further validate our findings, RT-qPCR and Western Blot analyses were employed, confirming differential expression of the identified eight key genes between the two groups. CONCLUSION: VPS13B, TBC1D22A, PPP3CA, CUX1 and PPP1R15A were identified as poor prognostic genes of cisplatin resistance in ovarian cancer, while PLGRKT, CDKAL1 and TAP1 were identified as good prognostic genes. This offers a novel perspective for future advancements in ovarian cancer treatment, suggesting potential avenues for the development of new therapeutic targets.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/uso terapêutico , Cisplatino/farmacologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Prognóstico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Linhagem Celular Tumoral , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , TranscriptomaRESUMO
More and more diterpenoids have attracted extensive attention due to the diverse chemical structures and excellent biological activities, and have been developed into clinical drugs or consumer products. The vast majority of diterpenoids are derived from plants. With the long-term development of plant medicinal materials, the natural resources of many plant diterpenoids are decreasing, and the biosynthetic mechanism of key active components has increasingly become a research hotspot. Using synthetic biology to engineer microorganisms into "cell factories" to produce the desired compounds is an essential means to solve these problems. In this review, we depict the plant-derived diterpenoids from chemical structure, biological activities, and biosynthetic pathways. We use representative plant diterpenes as examples to expound the research progress on their biosynthesis, and summarize the heterologous production of plant diterpenoids in microorganisms in recent years, hoping to lay the foundation for the development and application of plant diterpenoids in the future.
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The improvement of performance and yield in both cultivar and species mixtures has been well established. Despite the clear benefits of crop mixtures to agriculture, identifying the critical mechanisms behind performance increases are largely lacking. We experimentally demonstrated that the benefits of rice cultivar mixtures were linked to relatedness-mediated intraspecific neighbour recognition and discrimination under both field and controlled conditions. We then tested biochemical mechanisms of responses in incubation experiments involving the addition of root exudates and a root-secreted signal, (-)-loliolide, followed by transcriptome analysis. We found that closely related cultivar mixtures increased grain yields by modifying root behaviour and accelerating flowering over distantly related mixtures. Importantly, these responses were accompanied by altered concentration of signalling (-)-loliolide that affected rice transcriptome profiling, directly regulating root growth and flowering gene expression. These findings suggest that beneficial crop combinations may be generated a-priori by manipulating neighbour genetic relatedness in rice cultivar mixtures and that root-secreted (-)-loliolide functions as a key mediator of genetic relatedness interactions. The ability of relatedness discrimination to regulate rice flowering and yield raises an intriguing possibility to increase crop production.
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This work introduces a pioneering approach in the development of organic thin-film transistors (OTFTs), featuring a double-layer dielectric structure that combines poly(para-xylylene)s (Parylene) and poly(methyl methacrylate) (PMMA) to leverage the high insulation properties and high surface polarity of Parylene with the low insulation properties and low surface polarity of PMMA. This combination results in devices that showcase significantly enhanced electrical performance, including superior charge carrier mobility, increased current on/off ratios, and greater transconductance. Utilizing poly(3-hexylthiophene) (P3HT) for the active layer, the study demonstrates the advantage of the dual dielectric layers in minimizing hysteresis in the transfer curve, thereby facilitating the systematic growth of the organic active layer and enhancing electrical conductivity over single-layer alternatives. The superior performance of the Parylene/PMMA double-layer insulating structure opens new avenues for the advancement of organic electronics, presenting methodologies for performance optimization and expanding the application spectrum of OTFTs.
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Domesticação , Genoma de Planta , Glycine max , Telômero , Glycine max/genética , Telômero/genética , Evolução MolecularRESUMO
Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint.
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Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Receptores de Antígenos de Linfócitos T , Análise de Célula Única , Transcriptoma , Tuberculose Pulmonar , Tuberculose Pulmonar/imunologia , Humanos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Feminino , Mycobacterium tuberculosis/imunologia , Adulto , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Exaustão das Células TRESUMO
CO2-to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO2-x/TiO2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO2 nanorod surface. The as-synthesized Fe-TiO2-x/TiO2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO2 adsorption; iii) the Fe-TiO2-x/TiO2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO2-x/TiO2 homojunction exhibits superior CO2 reduction performances with optimized CO/CH4 generation rates of 122/22 µmol g-1h-1 which exceed those of pure TiO2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO2 reduction and beyond.
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Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.
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Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.
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Abrus precatorius is an herbaceous, flowering plant that is widely distributed in tropical and subtropical regions. Its toxic component, known as abrin, is classified as one of the potentially significant biological warfare agents and bioterrorism tools due to its high toxicity. Abrin poisoning can be utilized to cause accidents, suicides, and homicides, which necessitates attention from clinicians and forensic scientists. Although a few studies have recently identified the toxicological and pharmacological mechanisms of abrin, the exact mechanism remains unclear. Furthermore, the clinical symptoms and pathological changes induced by abrin poisoning have not been fully characterized, and there is a lack of standardized methods for identifying biological samples of the toxin. Therefore, there is an urgent need for further toxicopathologic studies and the development of detection methods for abrin in the field of forensic medicine. This review provides an overview of the clinical symptoms, pathological changes, metabolic changes, toxicologic mechanisms, and detection methods of abrin poisoning from the perspective of forensic toxicology. Additionally, the evidence on abrin in the field of forensic toxicology and forensic pathology is discussed. Overall, this review serves as a reference for understanding the toxicological mechanism of abrin, highlighting the clinical applications of the toxin, and aiding in the diagnosis and forensic identification of toxin poisoning.
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Abrina , Toxicologia Forense , Abrina/toxicidade , Humanos , Toxicologia Forense/métodos , Abrus/químicaRESUMO
Endometriosis, a common chronic gynecological disease, refers to the presence and proliferation of endometrial tissue in locations other than the uterine cavity. Approximately 6 to 10% of the population of women of childbearing age are known to have endometriosis; the most common clinical signs are pelvic pain and infertility. Although endometriosis is a benign disease, it exhibits some typical features of malignant tumors, such as proliferation, invasion, metastasis, and recurrence. Endometriosis is considered a chronic, inflammatory, and estrogen-dependent disease, and multiple factors contribute to its occurrence and development. In recent years, increasing attention has been given to the role of apoptosis in the pathogenesis of this disease. Some researchers believe that spontaneous apoptosis of the endometrium is critical in maintaining its normal structure and function, and abnormal apoptosis can promote the occurrence and development of endometriosis. Inflammation is another likely process in the pathogenesis of endometriosis. Inflammation mediates the adhesion, proliferation, differentiation, and invasion of ectopic lesions of endometriosis, primarily by regulating the function of immune cells and increasing the level of proinflammatory cytokines in body fluids. The ultimate initiators of apoptosis and inflammatory cell death (pyroptosis) are the caspase family proteases. In this article, we review the progress in recent years in caspase function as well as the possible role of these enzymes in the pathogenesis of endometriosis, indicating potential treatment strategies.
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Apoptose , Caspases , Endometriose , Endometriose/enzimologia , Endometriose/patologia , Endometriose/metabolismo , Humanos , Feminino , Caspases/metabolismo , Animais , Endométrio/patologia , Endométrio/enzimologia , Endométrio/metabolismoRESUMO
Aniline compounds, as a class of widely used but highly toxic chemical raw materials, are increasingly being released and accumulated in the environment, posing serious threats to environmental safety and human health. Therefore, developing detection methods for aniline compounds is of particular significance. Herein, we synthesized the fluorescent third monomer cyano-stilbene epoxide M and ternary copolymerized it with carbon dioxide (CO2) and propylene oxide (PO) to synthesize carbon dioxide-based polycarbonate (PPCM) with fluorescence recognition functions, as well as excellent performance, for the first time. The results revealed that the PPCM fluorescent probe exhibited typical aggregation-induced luminescence properties and could be quenched by aniline compounds. The probe presented anti-interference-specific selectivity for aniline compounds, and the detection limit was 1.69 × 10-4 M. Moreover, it was found to be a highly sensitive aniline detection probe. At the same time, the aniline biomarker p-aminophenol in urine could also be detected, which could expand the potential applications of polymers in the fluorescence-sensing field.
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Cancer cell resistance presents a significant clinical challenge. The mechanisms underlying drug resistance in cancer cells are intricate and remain incompletely understood. Notably, tumor cell resistance often coincides with the epithelial-mesenchymal transition (EMT). In this study, we observed an elevation in autophagy levels following the development of drug resistance in oesophageal cancer cells. Inhibition of autophagy led to a reduction in drug-resistant cell migration and the inhibition of EMT. Furthermore, we identified an upregulation of SIRT1 expression in drug-resistant oesophageal cancer cells. Subsequent inhibition of SIRT1 expression in drug-resistant cells resulted in the suppression of autophagy levels, migration ability, and the EMT process. Our additional investigations revealed that a SIRT1 inhibitor effectively curbed tumor growth in human oesophageal cancer xenograft model mice (TE-1, TE-1/PTX) without evident toxic effects. This mechanism appears to be associated with the autophagy levels within the tumor tissue.
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Autofagia , Neoplasias Esofágicas , Sirtuína 1 , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/tratamento farmacológico , Sirtuína 1/metabolismoRESUMO
In the field of oxide thermoelectrics, perovskite CaMnO3 ceramics have drawn plenty of attention due to their chemical stability, low cost, and environmental friendliness. By employing Ruddlesden-Poppe phase Ca3Mn2O7 as a precursor, the plate-like CaMnO3 microcrystals were successfully synthesized by the molten salt method combined with topochemical microcrystal conversion (TMC). The plate-like morphology of CaMnO3 was coordinately optimized by modulating the crystal structure of MnO2 and the molten salt environment. Plate-like microcrystals with an average size of â¼14.55 µm and a thickness of â¼2.89 µm were obtained by TMC reaction, demonstrating an obvious anisotropy. When ß-MnO2 was used as the raw material, a length-thickness ratio of 4.77 was obtained, which was attributed to the fact that CaMnO3 inherited the plate-like morphology of the Ca3Mn2O7 precursor during the TMC. The results confirm that the plate-like CaMnO3 microcrystals with obvious anisotropy can provide excellent template seeds for high-quality CaMnO3-based textured ceramics.
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BACKGROUND: Breast cancer susceptibility gene 1 (BRCA1) is a well-known gene that acts a vital role in suppressing the growth of tumors. Previous studies have primarily focused on the genetic mutations of BRCA1 and its association with hereditary breast invasive carcinoma (BRCA). However, little research has been done to investigate the relationship between BRCA1 and immune infiltrates and prognosis in BRCA. METHODS: We obtained the expression profiles and clinical information of patients with BRCA from the Cancer Genome Atlas (TCGA) database. The levels of the BRCA1 gene between BRCA tissues and normal breast tissues were compared through the Wilcoxon rank-sum test. Additionally, we performed WB and RT-qPCR techniques to detect the expression of BRCA1. We conducted functional enrichment analyses. Furthermore, we assessed immune cell infiltration using a single-sample gene set enrichment analysis. The methylation status of the BRCA1 gene was analyzed using the UALCAN and MethSurv databases. The Cox regression analysis and (KM) Kaplan-Meier method were employed to determine the prognostic value of BRCA1. In order to provide a practical tool for predicting the overall survival rates at different time points, we also constructed a nomogram. RESULTS: Our analysis revealed that the expression of BRCA1 was significantly higher in BRCA tissues compared to normal tissues. Furthermore, this increased level of BRCA1 was found to be associated with specific BRCA subtypes, including T2, stage II, ER positive, ect. Importantly, the overexpression of BRCA1 was shown to be a negative prognostic marker for the overall survival rates of BRCA patients. Moreover, low methylation status of the BRCA1 gene was related to a poorer prognosis. Furthermore, our results indicated that high levels of BRCA1 are related to a decrease in level of killer immune cells, such as natural killer (NK) cells, macrophages, CD8+ T cells, and plasma-like dendritic cells (pDCs) within the tumor microenvironment. CONCLUSIONS: Our study is the first to provide evidence indicating that the presence of BRCA1 can serve as a reliable marker for both diagnosing and determining the prognosis of BRCA. Moreover, BRCA1 acts as a crucial indicator of the cancer's potential to infiltrate and invade the immune system, which has important implications for developing targeted therapies in BRCA.
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Neoplasias da Mama , Linfócitos T CD8-Positivos , Humanos , Feminino , Prognóstico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Biologia Computacional , Microambiente Tumoral/genética , Proteína BRCA1/genéticaRESUMO
BACKGROUND: The 25-hydroxyvitamin D3 (25 (OH) D3) is crucial for follicular development. This study aimed to investigate the relationship between the level of 25 (OH) D3 in endometriosis patients, pregnancy outcomes of in vitro fertilization (IVF), and the underlying mechanism. METHODS: The 25 (OH) D3 levels in serum and follicular Fluid (FF) samples were detected using enzyme-linked immunosorbent assay (ELISA). Clinical features and pregnancy outcomes of endometriosis patients were also compared between the deficient group (< 20 ug/ml) and the adequate group (≥ 20 ug/ml). The effects of 25 (OH) D3 on the proliferation and cell cycle of human ovarian granulosa cells were respectively detected by CCK-8 assay and flow cytometry (FCM). The differentially expressed genes (DEGs) in granulosa cells of endometriosis and tubal infertility patients were screened from GEO database. The effects of 25 (OH) D3 on the expressions of CDKN2D, PPARA, TGFB2 and THBD were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: The levels of 25 (OH) D3 in serum and FF samples were decreased in endometriosis patients. The deficient group had fewer embryos that can be transferred, lower quality embryos and lower clinical pregnancy rates. Adequate 25 (OH) D3 levels in FF samples was a protective factor for live birth outcome in endometriosis patients. 25 (OH) D3 enhanced the proliferation capacity of granulosa cells (the concentration of 10 nM was the most significant) and increased the proportion of G2M + S phase cells. The expression of CDKN2D was decreased and TGFB2 and THBD were significantly upregulated. CONCLUSIONS: 25 (OH) D3 deficiency may be associated with poor IVF pregnancy outcomes in endometriosis patients. 25 (OH) D3 promotes ovarian granulosa cell proliferation by promoting the ability of cells to divide, and may accelerate cell cycle progression by up-regulating THBD and down-regulating CDKN2D expression.
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Endometriose , Gravidez , Feminino , Humanos , Endometriose/metabolismo , Resultado da Gravidez , Calcifediol/metabolismo , Fase S , Fertilização in vitro , Proliferação de Células/genética , Líquido Folicular/metabolismo , Células da Granulosa/metabolismoRESUMO
BACKGROUND: Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori). METHODS: The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms. RESULTS: Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs. CONCLUSION: H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.
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The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.
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Cotton fiber yield depends on the density of fiber cell initials that form on the ovule epidermis. Fiber initiation is triggered by MYB-MIXTA-like transcription factors (GhMMLs) and requires a sucrose supply. Ethylene or its precursor ACC (1-aminocyclopropane-1-carboxylic acid) is suggested to affect fiber yield. The Gossypium hirsutum (L.) genome contains 35 ACS genes (GhACS) encoding ACC synthases. Here, we explored the role of a GhACS family member in the regulation of fiber initiation. Expression analyses showed that the GhACS6.3 gene pair was specifically expressed in the ovules during fiber initiation (3 days before anthesis to 5 days post anthesis, -3 to 5 DPA), especially at -3 DPA, whereas other GhACS genes were expressed at very low or undetectable levels. The expression profile of GhACS6.3 during fiber initial development was confirmed by qRT-PCR analysis. Transgenic lines overexpressing GhACS6.3 (GhACS6.3-OE) showed increased ACC accumulation in ovules, which promoted the formation of fiber initials and fiber yield components. This was accompanied by increased transcript levels of GhMML3 and increased transcript levels of genes encoding sucrose transporters and sucrose synthase. These findings imply that GhACS6.3 activation is required for fiber initial development. Our results lay the foundation for further research on increasing cotton fiber production.
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BACKGROUND: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are common male diseases whose incidence rates gradually increase with age. They seriously affect men's physical health and quality of life. This study aimed to identify new biomarkers for the diagnosis of BPH and PCa. METHODS: Two datasets, GSE28204 and GSE134051 (including human PCa and BPH), were downloaded from the GEO database. The batch effect was removed for merging, and then differential gene expression analysis was conducted to identify BPH and PCa cases. The diagnostic biomarkers of BPH and PCa were further screened using machine learning and bioinformatics. ROC curves were drawn to evaluate the diagnostic accuracy of the selected biomarkers. An online website and qPCR were used to preliminarily explore the expression levels of PCa biomarkers. The correlations between the expression of biomarkers and the tumor microenvironment, tumor mutation load and immunotherapy drugs were evaluated. RESULTS: We identified fifteen genes (CHRDL1, DES, FLNC, GSTP1, MYL9, TGFB3, NEFH, TAGLN, SPARCL1, SYNM, TRPM8, HPN, PLA2G7, ENTPD5 and GPR160) as critical diagnostic biomarkers. After reviewing the literature on all selected biomarkers, we found few studies on the four genes CHRDL1, NEFH, TAGLN and SYNM in BPH or PCa. We defined these four genes as new potential diagnostic biomarkers (NPDBs) of BPH and PCa. All NPDBs were downregulated in PCa patients and PCa cell lines and upregulated in BPH patients and cell lines. When the immune landscape and mutation frequencies were analyzed, the results showed that the tumor microenvironment (TME), immune landscape, tumor mutation burden, and drug response were significantly correlated with NPDB expressions. CONCLUSIONS: We found four new diagnostic markers of BPH and PCa, which may facilitate the early diagnosis, treatment, and immunotherapeutic responses assessment and may be of major value in guiding clinical practice.