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BACKGROUND: Powdery mildew is a disease with one of the most substantial impacts on cucumber production globally. The most efficient approach for controlling powdery mildew is the development of genetic resistance; however, few genes associated with inherent variations in cucumber powdery mildew resistance have been identified as of yet. RESULTS: In this study, we re-sequence 299 cucumber accessions, which are divided into four geographical groups. A genome-wide association study identifies 50 sites significantly associated with natural variations in powdery mildew resistance. Linkage disequilibrium analysis further divides these 50 sites into 32 linkage disequilibrium blocks containing 41 putative genes. Virus-induced gene silencing and gene expression analysis implicate CsGy5G015960, which encodes a phosphate transporter, as the candidate gene regulating powdery mildew resistance. On the basis of the resequencing data, we generate five CsGy5G015960 haplotypes, identifying Hap.1 as the haplotype most likely associated with powdery mildew resistance. In addition, we determine that a 29-bp InDel in the 3' untranslated region of CsGy5G015960 is responsible for mRNA stability. Overexpression of CsGy5G015960Hap.1 in the susceptible line enhances powdery mildew resistance and phosphorus accumulation. Further comparative RNA-seq analysis demonstrates that CsGy5G015960Hap.1 may regulate cucumber powdery mildew resistance by maintaining a higher H2O2 level through the depletion of multiple class III peroxidases. CONCLUSIONS: Here we identify a candidate powdery mildew-resistant gene in cucumber using GWAS. The identified gene may be a promising target for molecular breeding and genetic engineering in cucumber to enhance powdery mildew resistance.
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Cucumis sativus , Resistência à Doença , Estudo de Associação Genômica Ampla , Desequilíbrio de Ligação , Doenças das Plantas , Cucumis sativus/genética , Cucumis sativus/microbiologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Ascomicetos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , HaplótiposRESUMO
Madelung disease is an uncommon metabolic disorder of uncertain pathogenesis, distinguished by the symmetric accumulation of nonencapsulated adipose tissue within the subcutaneous layer of the neck, abdomen, thighs, and other anatomical regions. This condition has been tightly connected with comorbidities including diabetes, dyslipidemia, hyperuricemia, hypothyroidism, and adrenal dysfunction, as well as sensory, motor, and autonomic polyneuropathy. The prevalence of Madelung disease is conspicuously higher in Mediterranean and Eastern European, with a distinct scarcity within the Asian population. Surgical interventions involving lipectomy and liposuction represent the foremost and most efficacious treatment approach. Herein, we present a case encompassing type II Madelung disease featuring bilateral thighs adipose tissue accumulation. The patient exhibited unexplained priapism alongside multiple venous thrombosis during four surgical interventions. The infrequent manifestation of postoperative hypercoagulability in patients of Madelung disease merits broad attention, owing to the potentiality for extensive venous thrombosis and consequential severe outcomes such as pulmonary embolism or cerebral infarction arising from thrombus dislodgment. Building upon this clinical scenario, we systematically documented the clinical manifestations and disease progression in this patient, meticulously analyzed the causes of complications, and proposed targeted preventive measures. Additionally, we conducted a comprehensive review of the relevant literature to summarize the clinical and epidemiological features of Madelung disease and to elucidate its mechanisms. This study will provide a valuable reference for future clinical treatments and mitigate perioperative complications of Madelung disease.
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The study by Zheng et al. (2024) identifies a NAC transcription factor, SOMBRERO (SMB), localized in the root cap of Arabidopsis, which is essential for root halotropism. SMB influences root halotropism by establishing asymmetric auxin distribution in the lateral root cap (LRC) and maintaining the expression of the auxin influx carrier gene AUX1. This mechanism leads to directional root bending away from high salinity areas. The findings reveal the SMB-AUX1-auxin module as a crucial mediator in root cap signaling and root halotropic response.
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BACKGROUND: HPV-16 infection and viral-host integration are the most important risk factors for cervical cancer (CC). The aim of this study is to develop a new molecular strategy integrated both the viral and host genome variations identifying and monitoring CC. METHOD: A total of 312 methylation and 538 RNA-seq datasets were collected from public databases to identify differentially methylated and expressed genes. HPV associated virus integration sites (VISs) were analysed using the ViMIC database. From September 2020 to August 2021, the 70 HPV-16 positive cases retrospectively collected from multi-centre cohorts were subjected to HPV-16 E6 deep sequencing and PCR-based host gene (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671) methylation detection. RNAseq and expression validation (NNF671) were performed in C-33A cell line harbouring HPV D32E. Lasso and logistic regression algorithm were used to construct the CC diagnostic model. RESULTS: A positive correlation was observed between the average methylation level of CC patients and their pathological features including tumour stage (p = 0.0077) and HPV subtype (p < 0.001). ZNF671 was identified as a CC-specific methylation marker, with an impressive 93% sensitivity. Both HPV-16 D32E mutation and integration of HPV-16 down-regulated the ZNF671 expression. Finally, a CC diagnostic nomogram was developed by integrating ZNF671 methylation level and HPV E6 mutation feature, yielding an exceptional AUC of 0.997 (95% CI: 0.934-1.000). CONCLUSIONS: Our study demonstrated HPV viral mutations are closely related to host gene epigenetic alterations in CC. Integration of the viral and host genetic information might be a new promising strategy for CC screening.
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X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.
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Subunidade gama Comum de Receptores de Interleucina , Tuberculose , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X , Humanos , Lactente , Masculino , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Éxons , Subunidade gama Comum de Receptores de Interleucina/genética , Mutação , Mycobacterium bovis/imunologia , Mycobacterium bovis/patogenicidade , Tuberculose/imunologia , Tuberculose/prevenção & controle , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/diagnóstico , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologiaRESUMO
The strategic design of catalysts for the oxygen evolution reaction (OER) is crucial in tackling the substantial energy demands associated with hydrogen production in electrolytic water splitting. Despite extensive research on birnessite (δ-MnO2) manganese oxides to enhance catalytic activity by modulating Mn3+ species, the ongoing challenge is to simultaneously stabilize Mn3+ while improving overall activity. Herein, oxygen (O) vacancies and nitrogen (N) doping have been simultaneously introduced into the MnO2 through a simple nitrogen plasma approach, resulting in efficient OER performance. The optimized N-MnO2v electrocatalyst exhibits outstanding OER activity in alkaline electrolyte, reducing the overpotential by nearly 160 mV compared to pure pristine MnO2 (from 476 to 312 mV) at 10 mA cm-2, and a small Tafel slope of 89 mV dec-1. Moreover, it demonstrates excellent durability over a 122 h stability test. The introduction of O vacancies and incorporation of N not only fine-tune the electronic structure of MnO2, increasing the Mn3+ content to enhance overall activity, but also play a crucial role in stabilizing Mn3+, thereby leading to exceptional stability over time. Subsequently, density functional theory calculations validate the optimized electronic structure of MnO2 achieved through the two engineering methods, effectively lowering the intermediate adsorption free energy barrier. Our synergistic approach, utilizing nitrogen plasma treatment, opens a pathway to concurrently enhance the activity and stability of OER electrocatalysts, applicable not only to Mn-based but also to other transition metal oxides.
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(1) Background: Prolonged coexposure to environmental contaminants is reportedly associated with adverse impacts on skin health. However, the collective effects of contaminant mixtures on psoriasis prevalence remain unclear. (2) Methods: A nationally representative cohort study was conducted using data from the National Health and Nutrition Examination Survey 2003-2006 and 2009-2014. The association between contaminant exposures and psoriasis prevalence was analyzed through weighted quantile sum regressions, restricted cubic splines, and multivariable logistic regression. (3) Results: 16,453 participants and 60 contaminants in 8 groups were involved. After adjusting for demographics and comorbidities, exposure to urinary perchlorate, nitrate, and thiocyanate mixtures (OR: 1.10, 95% CI: 1.00-1.21) demonstrated a significant positive linear association with psoriasis prevalence. Ethyl paraben (OR: 1.21, 95% CI: 1.02-1.44) exhibited a significant positive correlation with psoriasis risk as an individual contaminant. The association between blood cadmium, lead, and mercury mixtures (OR: 1.10, 95% CI: 1.00-1.21), urinary perchlorate, nitrate, and thiocyanate mixtures (OR: 1.16, 95% CI: 1.00-1.34), and psoriasis prevalence was more pronounced in the lower healthy lifestyle score subgroup. (4) Conclusions: Exposure to perchlorate, nitrate, and thiocyanate mixtures, and ethyl paraben was associated with an elevated psoriasis prevalence. Furthermore, the association between cadmium and lead and mercury mixtures as well as perchlorate, nitrate and thiocyanate mixtures, and psoriasis prevalence was more pronounced in individuals with less healthy lifestyles.
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Chloroplasts are not only critical photosynthesis sites in plants, but they also participate in plastidial retrograde signaling in response to developmental and environmental signals. MEcPP (2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate) is an intermediary in the methylerythritol phosphate (MEP) pathway in chloroplasts. It is a critical precursor for the synthesis of isoprenoids and terpenoid derivatives, which play crucial roles in plant growth and development, photosynthesis, reproduction, and defense against environmental constraints. Accumulation of MEcPP under stressful conditions triggers the expression of IMPα-9 and TPR2, contributing to the activation of abiotic stress-responsive genes. In this correspondence, we discuss plastidial retrograde signaling in support of a recently published paper in Molecular Plant (Zeng et al. 2024). We hope that it can shed more insight on the retrograde signaling cascade.
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Cloroplastos , Estresse Fisiológico , Cloroplastos/metabolismo , Regulação da Expressão Gênica de Plantas , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/metabolismo , Eritritol/metabolismo , Eritritol/análogos & derivados , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fosfatos Açúcares/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , MAP Quinase Quinase Quinase 5/genéticaRESUMO
BACKGROUND: Changes in the expression of genes related to glycosyltransferases may lead to alterations in N-glycan structure abundance, potentially acting as markers for diagnosis and prognosis in biliary tract cancer (BTC). METHODS: This study was divided into cross-sectional and longitudinal approaches. The cross-sectional study included 316 BTC and 301 non-BTC. Propensity score matching was applied to adjust for sex and age differences between BTC and non-BTC. Univariate and multivariate logistic regression identified independent risk factors for BTC and constructed the BTC-G model. The ROC curve was used to validate the diagnostic performance of BTC-G. Longitudinal follow-up studies included postoperative (N = 50) and immunotherapy (N = 43) follow-up cohorts. Cox regression analysis identified N-glycan structures impacting BTC prognosis postoperative and immunotherapy, with further confirmation through Kaplan-Meier curves. RESULTS: Univariate and multivariate analyses identified Peak3 (OR: 0.790, 95% CI: 0.658-0.949), Peak9 (OR: 1.646, 95% CI: 1.409-1.922), and Peak9p (OR: 2.467, 95% CI: 1.267-4.804) as independent BTC risk factors, leading to the creation of the BTC-G. The ROC curve confirmed that BTC-G performed well in training (AUC: 0.753, 95% CI: 0.703-0.799), validation (AUC: 0.811, 95% CI: 0.740-0.870), and CA19-9 negative cohorts (AUC: 0.717, 95% CI: 0.664-0.767). Cox regression analysis and Kaplan-Meier curves established that Peak12 (HR: 5.578, 95% CI: 1.145-27.170) and Peak11 (HR: 1.104, 95% CI: 0.611-1.994) are independent risk factors for BTC prognosis following surgery and immunotherapy, respectively. CONCLUSIONS: Our NGFP technology supplements BTC diagnostics, distinguishing survival and recurrence subtypes for postoperative and immunotherapy, thereby supporting the development of treatment strategies.
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Neoplasias do Sistema Biliar , Biomarcadores Tumorais , Polissacarídeos , Humanos , Masculino , Feminino , Polissacarídeos/sangue , Neoplasias do Sistema Biliar/sangue , Neoplasias do Sistema Biliar/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/sangue , Estudos Transversais , Idoso , Estudos Longitudinais , Curva ROC , Pontuação de PropensãoRESUMO
Lifestyles maybe associated with the immune and inflammatory state of human body. We aimed to comprehensively explore the relationship between lifestyles and circulating immune-inflammatory markers in the general population. Data from NHANES 1999-2014 was used. Lifestyle factors included leisure-time physical activity (LTPA), diet quality (Healthy Eating Index-2015, HEI-2015), alcohol consumption, cigarettes smoking, sleep hour and sedentary time. Immune makers included C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR). Generalized linear regression models were used to adjust confounders. Regressions of restricted cubic splines were utilized to evaluate the potentially non-linear relationships between exposures and outcomes. As results, HEI was negatively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P < 0.001). Cigarettes per day was positively associated with CRP (P < 0.001), SII (P < 0.001), and NLR (P = 0.008). Alcohol consumption was negatively associated with CRP (P < 0.001), but positively associated with PLR (P = 0.012) and MLR (P < 0.001). Physical activity was negatively associated with CRP (P < 0.001), SII (P = 0.005), and NLR (P = 0.002), but positively associated with PLR (P = 0.010). Participants with higher healthy lifestyle score had significantly lower CRP, SII and NLR (all P values < 0.05). Most of the sensitivity analyses found similar results. In conclusion, we found significant associations between lifestyles and immune markers in the general population, which may reflect a systemic inflammatory response to unhealthy lifestyles.
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Biomarcadores , Proteína C-Reativa , Exercício Físico , Estilo de Vida , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Adulto , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Consumo de Bebidas Alcoólicas/sangue , Neutrófilos/imunologia , Inflamação/sangue , Linfócitos/imunologia , Idoso , Monócitos/imunologiaRESUMO
Waterlogging is a serious abiotic stress that drastically decreases crop productivity by damaging the root system. Jasmonic acid (JA) inhibits waterlogging-induced adventitious root (AR) formation in cucumber (Cucumis sativus L.). However, we still lack a profound mechanistic understanding of how JA governs AR formation under waterlogging stress. JAZ (JASMONATE ZIM-DOMAIN) proteins are responsible for repressing JA signaling in a transcriptional manner. In this study, we showed that overexpressing CsJAZ8 inhibited the formation of ARs triggered by waterlogging. Molecular analyses revealed that CsJAZ8 inhibited the activation of the R2R3-MYB transcription factor CsMYB6 via direct interaction. Additionally, silencing of CsMYB6 negatively impacted AR formation under waterlogging stress, as CsMYB6 could directly bind to the promoters of 1-aminocyclopropane-1-carboxylate oxidase2 gene CsACO2 and gibberellin 20-oxidases gene CsGA20ox2, facilitating the transcription of these genes. The overexpression of CsACO2 and CsGA20ox2 led to increased levels of ethylene and gibberellin, which facilitated AR formation under waterlogging conditions. On the contrary, silencing these genes resulted in contrasting phenotypes of AR formation. These results highlight that the transcriptional cascade of CsJAZ8 and CsMYB6 plays a critical role in regulating hormonal-mediated cucumber waterlogging-triggered AR formation by inhibiting ethylene and gibberellin accumulation. We anticipate that our findings will provide insights into the molecular mechanisms that drive the emergence of AR in cucumber plants under waterlogging stress.
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BACKGROUND: Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. METHODS: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. RESULTS: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. CONCLUSION: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.
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Dermatite Atópica , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Dermatite Atópica/sangue , Dermatite Atópica/genética , Humanos , Lipídeos/sangue , Triglicerídeos/sangue , Fosfatidiletanolaminas/sangue , Fosfatidilcolinas/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5ethynyl2'deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcriptionquantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 ßgalactoside α2,6sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective antiICC candidate from two rounds highthroughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NFκB activation and reducing nuclear phosphorylatedNFκB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NFκB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.
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Neoplasias dos Ductos Biliares , Proliferação de Células , Colangiocarcinoma , Digitoxina , Transdução de Sinais , Humanos , Antígenos CD/metabolismo , Antígenos CD/genética , beta-D-Galactosídeo alfa 2-6-Sialiltransferase/metabolismo , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Digitoxina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/metabolismo , Sialiltransferases/genética , Sialiltransferases/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Climate change-induced weather events, such as extreme temperatures, prolonged drought spells, or flooding, pose an enormous risk to crop productivity. Studies on the implications of multiple stresses may vary from those on a single stress. Usually, these stresses coincide, amplifying the extent of collateral damage and contributing to significant financial losses. The breadth of investigations focusing on the response of horticultural crops to a single abiotic stress is immense. However, the tolerance mechanisms of horticultural crops to multiple abiotic stresses remain poorly understood. In this review, we described the most prevalent types of abiotic stresses that occur simultaneously and discussed them in in-depth detail regarding the physiological and molecular responses of horticultural crops. In particular, we discussed the transcriptional, posttranscriptional, and metabolic responses of horticultural crops to multiple abiotic stresses. Strategies to breed multi-stress-resilient lines have been presented. Our manuscript presents an interesting amount of proposed knowledge that could be valuable in generating resilient genotypes for multiple stressors.
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Produtos Agrícolas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Produtos Agrícolas/genética , Secas , Mudança Climática , Horticultura/métodosRESUMO
White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low-grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity-related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.
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The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.
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Microbioma Gastrointestinal , Imunoterapia , Neoplasias , Humanos , Microbioma Gastrointestinal/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , AnimaisRESUMO
Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator-like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow-brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow-colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C-terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3'H, which encodes flavonoid 3'-hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs.
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Cucumis sativus , Flavonoides , Frutas , Regulação da Expressão Gênica de Plantas , Pigmentação , Proteínas de Plantas , Fatores de Transcrição , Cucumis sativus/genética , Cucumis sativus/metabolismo , Frutas/genética , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Flavonoides/metabolismo , Pigmentação/genética , Estudo de Associação Genômica Ampla , Plantas Geneticamente ModificadasRESUMO
Abiotic stressors like waterlogging are detrimental to cucumber development and growth. However, comprehension of the highly complex molecular mechanism underlying waterlogging can provide an opportunity to enhance cucumber tolerance under waterlogging stress. We examined the hypocotyl and stage-specific transcriptomes of the waterlogging-tolerant YZ026A and the waterlogging-sensitive YZ106A, which had different adventitious rooting ability under waterlogging. YZ026A performed better under waterlogging stress by altering its antioxidative machinery and demonstrated a greater superoxide ion (O 2-) scavenging ability. KEGG pathway enrichment analysis showed that a high number of differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis. By pairwise comparison and weighted gene co-expression network analysis analysis, 2616 DEGs were obtained which were categorized into 11 gene co-expression modules. Amongst the 11 modules, black was identified as the common module and yielded a novel key regulatory gene, CsPrx73. Transgenic cucumber plants overexpressing CsPrx73 enhance adventitious root (AR) formation under waterlogging conditions and increase reactive oxygen species (ROS) scavenging. Silencing of CsPrx73 expression by virus-induced gene silencing adversely affects AR formation under the waterlogging condition. Our results also indicated that CsERF7-3, a waterlogging-responsive ERF transcription factor, can directly bind to the ATCTA-box motif in the CsPrx73 promoter to initiate its expression. Overexpression of CsERF7-3 enhanced CsPrx73 expression and AR formation. On the contrary, CsERF7-3-silenced plants decreased CsPrx73 expression and rooting ability. In conclusion , our study demonstrates a novel CsERF7-3-CsPrx73 module that allows cucumbers to adapt more efficiently to waterlogging stress by promoting AR production and ROS scavenging.