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Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.
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Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiologia , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Fotossíntese , Amido/metabolismo , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/genética , Grão Comestível/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo , Brassinosteroides/metabolismo , Esteroides Heterocíclicos/farmacologia , Esteroides Heterocíclicos/metabolismoRESUMO
Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSCs), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few research studies have explored the mechanism by which damaged ACs (DACs) contribute to PSCs activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSCs-suppressor to PSCs-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSCs. MiRNome profiling showed that let-7 family is significantly enriched in IAC-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSCs. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7 levels in AC-derived exosomes, and thus promoting PSCs activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSCs activation in CP, resulting in reduced pancreatic fibrosis. IAC-derived exosomes hold potential as potent weapons against PSCs activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.
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Células Acinares , Exossomos , Fibrose , Fator 4 Semelhante a Kruppel , MicroRNAs , Células Estreladas do Pâncreas , Pancreatite Crônica , Fator 4 Semelhante a Kruppel/metabolismo , Animais , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Exossomos/metabolismo , Pancreatite Crônica/metabolismo , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , MicroRNAs/genética , Células Acinares/metabolismo , Células Acinares/patologia , Dependovirus/genética , Camundongos , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Modelos Animais de Doenças , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Masculino , Técnicas de Cocultura , Pâncreas/metabolismo , Pâncreas/patologia , Terapia Genética/métodosRESUMO
Baculovirus budded virus (BV) acquires its envelope and viral membrane fusion proteins from the plasma membrane (PM) of the host cell during the budding process. However, this classical BV egress pathway has been questioned because an intracellularly localized membrane fusion protein, SPΔnGP64 (glycoprotein 64 [GP64] lacking the signal peptide [SP] n region), was assembled into the envelope to generate infective BVs in our recent studies. Here, we identify an additional pathway for Bombyx mori nucleopolyhedrovirus (BmNPV) BV assembly and release that differs, in part, from the currently accepted model for the egress pathway of baculovirus. Electron microscopy showed that during infection, BmNPV-infected cells contained many newly formed multivesicular body (MVB)-like compartments that included mature virions at 30 h postinfection (p.i.). Immunoelectron microscopy demonstrated that the MVBs contained CD63, an MVB endosome marker, and GP64, a BmNPV fusion glycoprotein. MVB fusion with the PM and the release of mature virions, together with naked nucleocapsids, were observed at the cell surface. Furthermore, MVB egress mediated the translocation of SPΔnGP64 to the PM, which induced cell-cell fusion until 36 h p.i. This BV egress pathway can be partially inhibited by U18666A incubation and RNA interference targeting MVB biogenesis genes. Our findings indicate that BmNPV BVs are enveloped and released through MVBs via the cellular exosomal pathway, which is a subordinate BV egress pathway that produces virions with relatively inferior infectivity. This scenario has significant implications for the elucidation of the BmNPV BV envelopment pathway. IMPORTANCE BmNPV is a severe pathogen that infects mainly Bombyx mori, a domesticated insect of economic importance, and accounts for approximately 15% of economic losses in sericulture. BV production plays a key role in systemic BmNPV infection of larvae. Despite the progress made in the functional gene studies of BmNPV, BmNPV BV egress is ill-understood. This study reports a previously unreported MVB envelopment pathway in BmNPV BV egress. To our knowledge, this is the first report of a baculovirus using dual BV egress pathways. This specific BV egress mechanism explains the cause of the non-PM-localized SPΔnGP64-rescued gp64-null bacmid infectivity, elucidating the reason underlying the retention of SP by BmNPV GP64. The data obtained elucidate an alternate molecular mechanism of baculovirus BV egress.
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Bombyx , Nucleopoliedrovírus , Animais , Corpos Multivesiculares , Liberação de Vírus , Linhagem Celular , Nucleopoliedrovírus/genética , Nucleopoliedrovírus/metabolismo , Proteínas Virais de Fusão/genéticaRESUMO
Herein, we describe an effective method for the synthesis of 2-alkoxyamides and 1,2-diamines through visible-light-mediated difunctionalization of alkenes. N-Aminopyridinium salts were employed as appropriate precursors to generate key amidyl radical intermediates via a photoinduced single-electron transfer (SET) process. The amidyl radicals would react with alkenes, followed by oxidation and nucleophilic addition. Excellent functional group tolerance and good yields demonstrate the synthetic potential of this transformation.
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Short tandem repeat (STR) genotyping provides parental origin information about aneuploidy pregnancy loss and has become the current gold standard for hydatidiform mole diagnosis. STR genotyping diagnostic support most commonly relies on formalin-fixed paraffin-embedded samples, but maternal contamination is one of the most common issues based on traditional unstained sections. To evaluate the influence of hematoxylin and eosin (H&E) staining on DNA quality and STR genotyping, DNA was isolated from unstained, deparaffinized hydrated, and H&E-stained tissue sections (i.e. 3 groups) from each of 6 formalin-fixed paraffin-embedded placentas. The macrodissected view field, DNA quality, and polymerase chain reaction amplification efficiency were compared among groups. STR genotyping analysis was performed in both the test cohort (n = 6) and the validation cohort (n = 149). H&E staining not only did not interfere with molecular DNA testing of formalin-fixed paraffin-embedded tissue but also had a clearer macrodissected field of vision. In the test cohort, H&E-stained sections were the only group that did not exhibit maternal miscellaneous peaks in STR genotyping results. In the validation cohort, 138 (92.62%) cases yielded satisfactory amplification results without maternal contamination. Thus, H&E staining helped to reduce maternal contamination in STR genotyping for hydatidiform mole diagnosis, suggesting that H&E-stained sections can be incorporated into the hydatidiform mole molecular diagnostic workflow.
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Light-induced ligand-to-metal charge transfer (LMCT) has been utilized as a powerful strategy in various organic reactions. First-row transition metals, especially iron complexes, show good applications in this process. Fe(III)-Cl and Fe(III)-OR species are two key intermediates involved in the LMCT of iron complexes. This review highlights studies on LMCT of Fe(III)-OR species, including carboxylate-iron and alkoxy-iron species, in organic transformations. Reaction conditions, substrate scope and related mechanisms are discussed.
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In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context.
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Carcinoma Ductal Pancreático , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia , MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Fatores de Transcrição de Domínio TEA , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição de Domínio TEA/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: The delayed drying of newly harvested tiger nuts can lead to mold and rancidity. Timely drying is therefore important. However, few studies have analyzed the impact of hot-air drying on the quality of tiger-nut oil and starch, making it essential to establish optimal drying conditions. RESULTS: The results showed that the drying temperature was the most important factor affecting the drying speed, followed by drying airflow rate and loading capacity. A logarithmic model can describe the hot-air drying process of tiger nuts. The oil yield of tiger nut was highest after drying at 60 °C, reaching 22.40%. Meanwhile, the starch extracted from after drying at 60 °C had the highest solubility and expansion rate, 4.77% and 9.74%, respectively. Starch has the highest viscosity after drying at 70 °C, and it forms gel easily after aging. CONCLUSION: High-quality tiger nuts should be produced under optimal conditions: a hot-air drying temperature of 60 °C, an airflow rate of 1.0 m s-1, and a loading capacity of 100 g. The results of this study have practical implications for the effective drying of tiger nuts. © 2024 Society of Chemical Industry.
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Carbon prediction on the township level is usually difficult due to a lack of necessary information. To fulfil the research gap, the study focused on a town located in a nearshore island (Lingshan) in China. A questionnaire survey was performed to collect essential information about the future development of the town, followed by validating interviews with the island management committee. The carbon prediction of the town was established by the Low Emissions Analysis Platform (LEAP) model. The baseline scenario reflecting the existing method of carbon management was compared with an alternative low-carbon scenario. The prediction from 2020 to 2060 covers the periods of the planned carbon emissions peak in 2030 and carbon neutrality in 2060. It is found that energy-related activities and electricity consumption are the primary contributors to carbon emissions on the island. The carbon emission of Lingshan Island increases from -1333 tCO2e in 2020 to 2744 tCO2e in 2060, and the carbon peak target cannot be achieved in the baseline scenario. However, the carbon emission of the low-carbon scenario is predicted to have a peak of -850 tCO2e in 2029. The prediction model developed in this study, along with the proposed policy recommendations, can be applied to other towns or regions where data availability is limited to promote carbon reduction.
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Carbono , Monitoramento Ambiental , China , Eletricidade , Condições SociaisRESUMO
A visible-light-promoted research protocol for constructing dihydropyrido[1,2-a]indolone skeletons is herein described proceeding through a cascade cyclization mediated by trifluoromethyl radicals. This method allows the efficient synthesis of various indole derivatives without the need of photocatalysts or transition-metal catalysts. Mechanism experiments indicate that the process involves a radical chain process initiated by the homolysis of Umemoto's reagent. This straightforward method enables a rapid access to heterocycles containing a trifluoromethyl group.
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ß-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods are mainly achieved by amino(hetero)arylation reaction with the aid of transition metals and preactivated substrates. Herein, we report a metal-free and photoinduced intermolecular amino(hetero)arylation reaction for the single-step installation of both (hetero)aryl and iminyl groups across alkenes in an efficient and regioselective manner. This method shows broad scope (up to 124 examples) and excellent tolerance of various olefinsâfrom the simplest ethylene to complex multisubstituted alkenes can all participate in the reaction. Furthermore, aminosulfonylation of alkenes can be also conducted in the presence of sodium bisulfite as the SO2 source.
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BACKGROUND: Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. METHOD: Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. RESULTS: The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = -3.161, p = 0.007] and 16 (LS mean difference = -3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. CONCLUSIONS: Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.
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Transtorno Depressivo Maior , Psicoterapia Psicodinâmica , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/uso terapêutico , Resultado do Tratamento , Terapia CombinadaRESUMO
BACKGROUND: Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke. METHODS: Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor. RESULTS: Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility. CONCLUSIONS: Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.
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Dieta , Acidente Vascular Cerebral , Dieta/efeitos adversos , Humanos , Incidência , Metanálise como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologiaRESUMO
A series of 9H-purin-6-amine derivatives as aldose reductase (ALR) inhibitors were designed and synthesized. Most of these derivatives, having a C6-substituted benzylamine side chain and N9 carboxylic acid on the core structure, were found to be potent and selective ALR inhibitors, with submicromolar IC50 values against ALR2. Particularly, compound 4e was the most active with an IC50 value of 0.038 µM, and it was also proved to be endowed with excellent inhibitory selectivity. The structure-activity relationship and molecular docking studies highlighted the importance of the carboxylic acid head group along with different halogen substituents on the C6 benzylamine side chain of the 9H-purin-6-amine scaffold for the construction of strong and selective ALR inhibitors.
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Complicações do Diabetes , Diabetes Mellitus , Aldeído Redutase , Aminas , Benzilaminas , Ácidos Carboxílicos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Relação Estrutura-AtividadeRESUMO
The regional management on greenhouse gas (GHG) emissions is essential to the success of global carbon reduction. However, previous studies mostly focused on the city or country levels, while the management of GHG emissions on the township level has not been fully studied. This study proposed a framework of carbon management on the township level and developed a calculation tool for accounting GHG emissions. The case study of Lingshan Island, located in eastern China, was conducted through a site visit and interviews. A questionnaire survey was performed to collect data for carbon accounting. It is found that the island had a negative carbon emission of -1336 t CO2e in 2020, which is mostly contributed from energy and electricity consumption. Due to the COVID-19 pandemic, the number of tourists decreased in 2020 and the carbon emission was 224 t CO2e lower than in 2019. The proposed framework consists of five steps and requires the collaboration of the government, the locals, researchers and other stakeholders. The framework was validated through a focus group meeting and the suggestions on carbon management at township level were provided. This study paves a way of carbon accounting and management for the less urbanized regions.
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COVID-19 , Gases de Efeito Estufa , COVID-19/epidemiologia , Carbono/análise , China , Efeito Estufa , Humanos , PandemiasRESUMO
BACKGROUND: Pneumocystis jirovecii and Aspergillus fumigatus, are opportunistic pathogenic fungus that has a major impact on mortality in patients with systemic lupus erythematosus. With the potential to invade multiple organs, early and accurate diagnosis is essential to the survival of SLE patients, establishing an early diagnosis of the infection, especially coinfection by Pneumocystis jirovecii and Aspergillus fumigatus, still remains a great challenge. CASE PRESENTATION: In this case, we reported that the application of next -generation sequencing in diagnosing Pneumocystis jirovecii and Aspergillus fumigatus coinfection in a Chinese girl with systemic lupus erythematosus (SLE). Voriconazole was used to treat pulmonary aspergillosis, besides sulfamethoxazole and trimethoprim (SMZ-TMP), and caspofungin acetate to treat Pneumocystis jirovecii infection for 6 days. On Day 10 of admission, her chest radiograph displayed obvious absorption of bilateral lung inflammation though the circumstance of repeated fever had not improved. Unfortunately, the patient discharged from the hospital since the financial burden, and during the follow-up, it was documented the patient died within one week after discharge. CONCLUSIONS: This successful application of the next generation sequencing assisting the rapid diagnosis of Pneumocystis jirovecii and Aspergillus fumigatus coinfection provides a new perspective in the clinical approach against the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.
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Aspergillus fumigatus/isolamento & purificação , Coinfecção/diagnóstico , Coinfecção/microbiologia , Lúpus Eritematoso Sistêmico/complicações , Pneumocystis carinii/isolamento & purificação , Pneumonia/diagnóstico , Pneumonia/microbiologia , Adolescente , Aspergillus fumigatus/genética , Caspofungina , Coinfecção/tratamento farmacológico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lúpus Eritematoso Sistêmico/microbiologia , Infecções Oportunistas/microbiologia , Pneumocystis carinii/genética , Pneumonia/tratamento farmacológico , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêutico , Voriconazol/uso terapêuticoRESUMO
Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic biomarkers for the prediction of human complex diseases such as ischemic stroke (IS). However, so far, no reports have focused on the relationship of lncRNA polymorphisms with IS onset and prognosis. In our study, eight potential functional polymorphisms of four well-known lncRNAs (H19 rs2107425 and rs2251375, MALAT1 rs4102217 and rs3200401, MEG3 rs11160608 and rs4081134, SENCR rs4526784 and rs555172) were genotyped in 657 ischemic stroke patients. Then, the association between lncRNA polymorphisms and IS onset and recurrence were investigated. These lncRNA variants were not associated with age onset of IS. However, we observed that MEG3 rs4081134 AA genotype was statistically related with a reduced risk of stroke recurrence, particularly for patients with large-artery atherosclerotic stroke. Also, the decreased risk was more prominent in elders, non-smokers, non-drinkers and hypertensive patients. Furthermore, the variant genotype AA of rs4081134 was an independent predictor for IS recurrence using the multivariate Cox regression model. Our findings indicated that MEG3 rs4081134 can serve as a useful biomarker and potential therapeutic target in IS recurrence. More researches are needed to verify our results and explore the underlying molecular mechanisms.
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AVC Isquêmico/genética , RNA Longo não Codificante/genética , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biomarcadores , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/genética , Arteriosclerose Intracraniana/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Valor Preditivo dos Testes , Prognóstico , RecidivaRESUMO
MicroRNA binding site polymorphisms in immunoinflammatory genes have been implicated as candidate biomarkers for prediction of complex human diseases. However, the roles of microRNA binding site polymorphisms in stroke onset and prognosis remain unclear. Thus, for the first time, five potential functional polymorphisms in immunoinflammatory genes (CXCR2 rs1126579, TLR4 rs11536889, ADIPOR2 rs12342, MMP-2 rs7201 and MMP-9 rs1056628) were genotyped in 657 patients with ischemic stroke. These five polymorphisms were not related with age onset of ischemic stroke. However, we found that ADIPOR2 rs12342 was significantly associated with a decreased recurrence risk, especially for the patients with small-vessel disease. Moreover, by using multivariate Cox regression, the variant genotype GG/GA of rs12342 was observed as an independent protective factor for stroke recurrence, even after Bonferroni correction. In addition, after the addition of rs12342 in the model with clinical factors, the new model showed the improved discriminatory ability to predict stroke recurrence. In short, our results suggested that ADIPOR2 rs12342 may be a novel genetic biomarker and therapeutic target for ischemic stroke recurrence. Further studies are required to replicate our findings and clarify the potential biological mechanism.
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AVC Isquêmico/genética , MicroRNAs/metabolismo , Polimorfismo Genético , Idade de Início , Sítios de Ligação , Feminino , Humanos , Mediadores da Inflamação , Masculino , Pessoa de Meia-Idade , Receptores de Adiponectina/genética , RecidivaRESUMO
The association between polymorphisms in HOTAIR gene and cancer susceptibility has been analyzed intensively, but the conclusions are inconsistent. Therefore, we carried out a meta-analysis aiming to assess the relationship exactly. Eligible studies were searched in PubMed and Embase databases up to October 31, 2019. Odds ratios with 95% confidence intervals were used to assess the strength of association. Sensitivity analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results. Totally, 116 studies involving 122,832 subjects were analyzed in our meta-analysis. Significant increased risk of cancer was detected for the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms. Further subgroup analyses according to cancer type revealed that different polymorphisms were associated with the risk of specific type of cancer. For example, the rs4759314 polymorphism was significantly associated with the risk of estrogen-dependent cancer, whereas the rs920778 polymorphism was associated with the risk of gastrointestinal cancer. In conclusion, our findings indicated that the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms in HOTAIR may serve as genetic biomarkers of cancer.
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Neoplasias/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , HumanosRESUMO
Pseudomonas syringae, a major hemibiotrophic bacterial pathogen, causes many devastating plant diseases. However, the transcriptional regulation of plant defense responses to P. syringae remains largely unknown. Here, we found that gain-of-function of BTB AND TAZ DOMAIN PROTEIN 4 (BT4) enhanced the resistance of Arabidopsis (Arabidopsis thaliana) to Pst DC3000 (Pseudomonas syringae pv. tomato DC3000). Disruption of BT4 also weakened the salicylic acid (SA)-induced defense response to Pst DC3000 in bt4 mutants. Further investigation indicated that, under Pst infection, transcription of BT4 is modulated by components of both the SA and ethylene (ET) signaling pathways. Intriguingly, the specific binding elements of ETHYLENE RESPONSE FACTOR (ERF) proteins, including dehydration responsive/C-repeat elements and the GCC box, were found in the putative promoter of BT4 Based on publicly available microarray data and transcriptional confirmation, we determined that ERF11 is inducible by salicylic acid and Pst DC3000 and is modulated by the SA and ET signaling pathways. Consistent with the function of BT4, loss-of-function of ERF11 weakened Arabidopsis resistance to Pst DC3000 and the SA-induced defense response. Biochemical and molecular assays revealed that ERF11 binds specifically to the GCC box of the BT4 promoter to activate its transcription. Genetic studies further revealed that the BT4-regulated Arabidopsis defense response to Pst DC3000 functions directly downstream of ERF11. Our findings indicate that transcriptional activation of BT4 by ERF11 is a key step in SA/ET-regulated plant resistance against Pst DC3000, enhancing our understanding of plant defense responses to hemibiotrophic bacterial pathogens.