RESUMO
BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction (P<0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis (P<0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid-mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice (P<0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.
Assuntos
Plaquetas , Diacilglicerol Quinase , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Trombose , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Plaquetas/metabolismo , Trombose/prevenção & controle , Trombose/sangue , Trombose/enzimologia , Trombose/tratamento farmacológico , Humanos , Masculino , Diacilglicerol Quinase/antagonistas & inibidores , Diacilglicerol Quinase/metabolismo , Camundongos , Ativação Plaquetária/efeitos dos fármacos , Feminino , Agregação Plaquetária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Pessoa de Meia-Idade , Fibrinolíticos/farmacologia , Estudos de Casos e Controles , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/enzimologia , Obesidade/sangue , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
Accurate and comprehensive knowledge of the atmospheric environment and its evolution within the coastal ocean boundary layer are necessary for understanding the sources, chemical mechanisms, and transport processes of air pollution in land, sea, and atmosphere. We present an overview of coastal ocean boundary layer detection technology and equipment in China and summarize the progress and main achievements in recent years. China has developed a series of coastal ocean boundary layer detection technologies, including Light Detection and Ranging (LIDAR), turbulent exchange analyzer, air-sea flux analyzer, stereoscopic remote sensing of air pollutants, and oceanic aerosol detection equipment to address the technical bottleneck caused by harsh environmental conditions in coastal ocean regions. Advances in these technologies and equipment have provided scientific assistance for addressing air pollution issues and understanding land-sea-atmosphere interactions over coastal ocean regions in China. In the future, routine atmospheric observations should cover the coastal ocean boundary layer of China.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Oceanos e Mares , Tecnologia , ChinaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , COVID-19/prevenção & controle , Infecção Hospitalar/prevenção & controle , Controle de Infecções , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico , Ruptura Aórtica/diagnóstico , COVID-19/diagnóstico , COVID-19/transmissão , COVID-19/virologia , Teste para COVID-19 , China , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Emergências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Fluxo de TrabalhoRESUMO
Vascular metabolic dysfunction presents in various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. Due to the high prevalence of these diseases, it is important to explore treatment strategies to protect vascular function. Resveratrol (RSV), a natural polyphenolic phytochemical, is regarded as an agent to regulate metabolic pathways. Many studies have proven that RSV has beneficial effects on improving metabolism in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which provide new directions to treat vascular metabolic diseases. Herein, we overviewed that RSV could regulate cell metabolism activity by inhibiting glucose uptake, suppressing glycolysis, preventing cells from fatty acid-related damages, reducing lipogenesis, increasing fatty acid oxidation, enhancing lipolysis, elevating uptake and synthesis of glutamine, and increasing NO release. Furthermore, in clinical trials, although the results from different studies remain controversial, we proposed that RSV had better therapeutic effects at high concentrations and for patients with metabolic disorders.
Assuntos
Doenças Metabólicas , Estilbenos , Doenças Vasculares , Humanos , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Células Endoteliais/metabolismo , Doenças Metabólicas/tratamento farmacológico , Metabolismo dos Lipídeos , Ácidos Graxos/metabolismo , Estilbenos/farmacologiaRESUMO
Airborne black carbon is a strong warming component of the atmosphere. Therefore, curbing black carbon emissions should slow down global warming. The 2019 coronavirus pandemic (COVID-19) is a unique opportunity for studying the response of black carbon to the varied human activities, in particular due to lockdown policies. Actually, there is few knowledge on the variations of black carbon in China during lockdowns. Here, we studied the concentrations of particulate matter (PM2.5) and black carbon before, during, and after the lockdown in nine sites of the Yangtze River Delta in Eastern China. Results show 40-60% reduction of PM2.5 and 40-50% reduction of black carbon during the lockdown. The classical bimodal peaks of black carbon in the morning and evening rush hours were highly weakened, indicating the substantial decrease of traffic activities. Contributions from fossil fuels combustion to black carbon decreased about 5-10% during the lockdown. Spatial correlation analysis indicated the clustering of the multi-site black carbon concentrations in the Yangtze River Delta during the lockdown. Overall, control of emissions from traffic and industrial activities should be efficient to curb black carbon levels in the frame of a 'green public transit system' for mega-city clusters such as the Yangtze River Delta. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10311-021-01327-3.
RESUMO
The coronavirus (COVID-19) pandemic is disrupting the world from many aspects. In this study, the impact of emission variations on PM2.5-bound elemental species and health risks associated to inhalation exposure has been analyzed based on real-time measurements at a remote coastal site in Shanghai during the pandemic. Most trace elemental species decreased significantly and displayed almost no diel peaks during the lockdown. After the lockdown, they rebounded rapidly, of which V and Ni even exceeded the levels before the lockdown, suggesting the recovery of both inland and shipping activities. Five sources were identified based on receptor modeling. Coal combustion accounted for more than 70% of the measured elemental concentrations before and during the lockdown. Shipping emissions, fugitive/mineral dust, and waste incineration all showed elevated contributions after the lockdown. The total non-carcinogenic risk (HQ) for the target elements exceeded the risk threshold for both children and adults with chloride as the predominant species contributing to HQ. Whereas, the total carcinogenic risk (TR) for adults was above the acceptable level and much higher than that for children. Waste incineration was the largest contributor to HQ, while manufacture processing and coal combustion were the main sources of TR. Lockdown control measures were beneficial for lowering the carcinogenic risk while unexpectedly increased the non-carcinogenic risk. From the perspective of health effects, priorities of control measures should be given to waste incineration, manufacture processing, and coal combustion. A balanced way should be reached between both lowering the levels of air pollutants and their health risks.
Assuntos
Poluentes Atmosféricos , COVID-19 , Adulto , Poluentes Atmosféricos/análise , COVID-19/epidemiologia , Carcinógenos , Criança , China/epidemiologia , Carvão Mineral/análise , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Pandemias , Material Particulado/análise , Medição de Risco , Estações do AnoRESUMO
OBJECTIVE: The development of in-stent restenosis (ISR) hinders the long-term patency of carotid artery stenting (CAS), yet no optimal treatment has been established. In the present study, we compared the outcomes of redo CAS (rCAS) and carotid endarterectomy (CEA) for ISR. METHODS: A systematic search using the terms "in-stent restenosis," "carotid endarterectomy," and "carotid artery stenting" was conducted in the PubMed, Embase, and Cochrane databases. Studies reporting perioperative stroke, death, and other important complications of rCAS or CEA for ISR after previous CAS with four or more patients were included. Pooled and sensitivity analyses were conducted to synthesize and compare estimates of the outcomes. RESULTS: A total of 11 studies with 1057 patients who had undergone rCAS (n = 894) or CEA (n = 163) met the inclusion criteria. The CEA group had a significantly greater proportion of symptomatic patients (rCAS vs CEA, 30.4% vs 42.1%; P < .01). The duration from primary CAS to reintervention was relatively longer in the CEA group (rCAS vs CEA, median, 8.8 months [range, 3-26 months] vs 19.9 months [range, 0-54 months]). In the rCAS group, a greater proportion of patients had hypertension, hypercholesterolemia, and coronary artery disease and had received antiplatelet therapy before reintervention. Because of insufficient data or a low incidence, the only complications feasible for further analysis were restenosis, myocardial infarction, cranial nerve injury, and neck hematoma. No significant differences were found in the primary end point of mortality/stroke event-free rate (rCAS vs CEA, 99% vs 98%; P > .05) or other secondary end points (event-free restenosis, 100% vs 100%; event-free myocardial infarction, 100% vs 98%; event-free cranial nerve injury, 100% vs 98%; event-free neck hematoma, 100% vs 100% for rCAS vs CEA; P > .05 for all). CONCLUSIONS: rCAS is commonly used to treat patients with severe and/or symptomatic ISR after primary CAS. Although the endovascular approach is less invasive, both rCAS and CEA can be performed safely with similar short- and midterm outcomes of stroke, death, and surgery-related complications.
Assuntos
Estenose das Carótidas/terapia , Endarterectomia das Carótidas , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Retratamento , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI.
Assuntos
Isquemia Crônica Crítica de Membro/tratamento farmacológico , Proteína Forkhead Box O1/metabolismo , Neovascularização Patológica/tratamento farmacológico , Resveratrol/farmacologia , Animais , Isquemia Crônica Crítica de Membro/metabolismo , Proteína Forkhead Box O1/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
In this work, we report on the design of a wide-band digital lock-in amplifier (DLIA) of up to 65 MHz and its application for electrical impedance measurements in microfluidic devices. The DLIA is comprised of several dedicated technologies. First, it features a fully differential analog circuit, which includes a preamplifier with a low input noise of 4.4 nV/âHz, a programmable-gain amplifier with a gain of 52 dB, and an anti-aliasing, fully differential low-pass filter with -76 dB stop-band attenuation. Second, the DLIA has an all-digital phase lock loop, which features a phase deviation of less than 0.02° throughout the frequency range. The phase lock loop utilizes an equally accurate period-frequency measurement, with a sub-ppm precision of frequency detection. Third, a modified clock link is implemented in the DLIA to improve the signal-to-noise ratio of the analog-to-digital converter affected by clock jitter of up to 20 dBc. A series of measurements were performed to characterize the DLIA, and the results showed an accurate performance. Additionally, impedance measurements of standard-size microparticles were performed by frequency sweep from 300 kHz to 30 MHz, using the DLIA in a microfluidic device. Different diameters of microparticle could be accurately distinguished according to the relative impedance at 2.5 MHz. The results confirm the promising applications of the DLIA in microfluidic electrical impedance measurements.
RESUMO
This study assessed the safety and feasibility of 24-hour hospitalization after thyroid surgery. A randomized controlled trial study was performed for 432 patients scheduled for thyroidectomy in Guangdong General Hospital between January 2014 and January 2016. Group A cases (n = 216) were 24-hour hospital stay and group B cases (n = 216) were inpatient. Preoperative patient characteristics and operative characteristics as well surgical complications were evaluated. Two hundred and fourteen patients (99%) of group A were discharged after a 24-hour postoperative observation except 1 patient hospitalized 2 days for persistent nausea after surgery, and 1 patient who was hospitalized for 2 days for fear of the complication after the operation. The complication rates were similar between the 2 groups (9/216, 11/216; P > 0.05) and no one was readmitted for operation. The overall complication rate of 24-hour hospital stay procedure was low, and there were no differences in the rate of complications between these 2 groups. Thyroid surgery with 24-hour hospital stay is feasible and safe by experienced surgeon in a setting of appropriate facility and management protocol.
Assuntos
Hospitalização , Segurança , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
The origin of novel traits is recognized as an important process underlying many major evolutionary radiations. We studied the genetic basis for the evolution of haustoria, the novel feeding organs of parasitic flowering plants, using comparative transcriptome sequencing in three species of Orobanchaceae. Around 180 genes are upregulated during haustorial development following host attachment in at least two species, and these are enriched in proteases, cell wall modifying enzymes, and extracellular secretion proteins. Additionally, about 100 shared genes are upregulated in response to haustorium inducing factors prior to host attachment. Collectively, we refer to these newly identified genes as putative "parasitism genes." Most of these parasitism genes are derived from gene duplications in a common ancestor of Orobanchaceae and Mimulus guttatus, a related nonparasitic plant. Additionally, the signature of relaxed purifying selection and/or adaptive evolution at specific sites was detected in many haustorial genes, and may play an important role in parasite evolution. Comparative analysis of gene expression patterns in parasitic and nonparasitic angiosperms suggests that parasitism genes are derived primarily from root and floral tissues, but with some genes co-opted from other tissues. Gene duplication, often taking place in a nonparasitic ancestor of Orobanchaceae, followed by regulatory neofunctionalization, was an important process in the origin of parasitic haustoria.
Assuntos
Duplicação Gênica/genética , Orobanchaceae/genética , Transcriptoma/genética , Análise por Conglomerados , Evolução Molecular , Perfilação da Expressão Gênica , Genes de Plantas/genética , Mimulus/genética , Mimulus/fisiologia , Orobanchaceae/fisiologiaRESUMO
The sensitivity of biochemical effects on leaf reflectance is vital for retieving biochemical parameters with remote sensing. In this study, the chlorophyll and water absorption coefficients of the commonly used model LIBERTY (leaf incorporation biochemistry exhibiting reflectance and transmittance yields) were calibrated using field measured needle spectral reflectance curves based on a look up table (LUT) method. A novel spectra reflectance fitting method were presented by involving a new index (named as yellow index, YI), which could obviously improve the fitting accuracy of Pinus yunnanensis reflection spectrum at highly-stressed status. As a global sensitivity analysis method, the EFAST (extended Fourier amplitued sensitivity test) was implemented to quantitatively assess the sensitivity of biochemical parameters on needle reflectance. Results show that: (1) the reflectauce spectrum of healthy needles (R2=0.999ï¼RMSEï¼0.01), slightly stressed needles (R2=0.991, RMSEï¼0.02) and moderately stressed needles (R2=0.992ï¼RMSEï¼0.03) are simulated fairly well by calibrated LIBERTY model which has less potential in fitting the reflectance spectrum of seriously stressed needles (R2=0.803ï¼RMSEï¼0.1). (2) the reflectance spectrum of seriously stressed needles can be successfully simulated by our proposed spectrum reflectance fitting method (R2=0.991, RMSE<0.03), because YI can quantitatively describe different degrees of stress, and (3) the sensitivity of leaf reflectance to chlorophyll and water parameters decreases with the degree of stress; while the sensitivity to other biochemical parameters is increasing, which includ baseline absorption, albino absorption, Lignin and Cellulose content, and nitrogen content, increases with the stress degree. Needle reflectance spectrum also have sensitivive bands for these parameters. For example, the albino absorption have a significant effect on needle reflectance in 505ï½565 and 705ï½850 nm). In addition, Albino absorption and chlorophyll also have significant effects on needle reflectance in visible region for seriously stressed needles, which indicates that the prior knowledge of the albino absorption level can help obtain the valid inversion result of chlorophyll content.
Assuntos
Pinus , Clorofila , Agulhas , Nitrogênio , Folhas de Planta , Análise Espectral , ÁguaRESUMO
UNLABELLED: This paper evaluates the PM2.5- and ozone-related mortality at present (2000s) and in the future (2050s) over the continental United States by using the Environmental Benefits Mapping and Analysis Program (BenMAP-CE). Atmospheric chemical fields are simulated by WRF/CMAQ (horizontal resolution: 12×12 km), applying the dynamical downscaling technique from global climate-chemistry model under the Representative Concentration Pathways scenario (RCP 8.5). Future air quality results predict that the annual mean PM2.5 concentration in continental U.S. decreases nationwide, especially in the Eastern U.S. and west coast. However, the ozone concentration is projected to decrease in the Eastern U.S. but increase in the Western U.S. Future mortality is evaluated under two scenarios (1) holding future population and baseline incidence rate at the present level and (2) using the projected baseline incidence rate and population in 2050. For PM2.5, the entire continental U.S. presents a decreasing trend of PM2.5-related mortality by the 2050s in Scenario (1), primarily resulting from the emissions reduction. While in Scenario (2), almost half of the continental states show a rising tendency of PM2.5-related mortality, due to the dominant influence of population growth. In particular, the highest PM2.5-related deaths and the biggest discrepancy between present and future PM2.5-related deaths both occur in California in 2050s. For the ozone-related premature mortality, the simulation shows nation-wide rising tendency in 2050s under both scenarios, mainly due to the increase of ozone concentration and population in the future. Furthermore, the uncertainty analysis shows that the confidence interval of all causes mortality is much larger than that for specific causes, probably due to the accumulated uncertainty of generating datasets and sample size. The confidence interval of ozone-related all cause premature mortality is narrower than the PM2.5-related all cause mortality, due to its smaller standard deviation of the concentration-mortality response factor. IMPLICATIONS: The health impact of PM2.5 is more linearly proportional to the emission reductions than ozone. The reduction of anthropogenic PM2.5 precursor emissions is likely to lead to the decrease of PM2.5 concentrations and PM2.5 related mortality. However, the future ozone concentrations could increase due to increase of the greenhouse gas emissions of methane. Thus, to reduce the impact of ozone related mortality, anthropogenic emissions including criteria pollutant and greenhouse gas (i.e. methane) need to be controlled.
Assuntos
Poluentes Atmosféricos/toxicidade , Doenças Cardiovasculares/mortalidade , Mudança Climática , Exposição Ambiental , Ozônio/toxicidade , Material Particulado/toxicidade , Doenças Respiratórias/mortalidade , Doenças Cardiovasculares/induzido quimicamente , Monitoramento Ambiental , Geografia , Modelos Teóricos , Tamanho da Partícula , Doenças Respiratórias/induzido quimicamente , Estados Unidos/epidemiologiaRESUMO
Seed germination of Striga spp. (witchweeds), one of the world's most destructive parasitic weeds, cannot be induced by light but is specifically induced by strigolactones. It is not known whether Striga uses the same components for strigolactone signaling as host plants, whether it has endogenous strigolactone biosynthesis and whether there is post-germination strigolactone signaling in Striga. Strigolactones could not be detected in in vitro grown Striga, while for host-grown Striga, the strigolactone profile is dominated by a subset of the strigolactones present in the host. Branching of in vitro grown Striga is affected by strigolactone biosynthesis inhibitors. ShMAX2, the Striga ortholog of Arabidopsis MORE AXILLARY BRANCHING 2 (AtMAX2) - which mediates strigolactone signaling - complements several of the Arabidopsis max2-1 phenotypes, including the root and shoot phenotype, the High Irradiance Response and the response to strigolactones. Seed germination of max2-1 complemented with ShMAX2 showed no complementation of the Very Low Fluence Response phenotype of max2-1. Results provide indirect evidence for ShMAX2 functions in Striga. A putative role of ShMAX2 in strigolactone-dependent seed germination of Striga is discussed.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Proteínas de Transporte/genética , Germinação/genética , Lactonas/metabolismo , Caules de Planta/metabolismo , Sementes/metabolismo , Striga/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Genes de Plantas , Luz , Mutação , Fenótipo , Raízes de Plantas , Brotos de Planta , Caules de Planta/crescimento & desenvolvimento , Plantas Daninhas , Sementes/crescimento & desenvolvimento , Transdução de Sinais , Striga/crescimento & desenvolvimento , Striga/metabolismoRESUMO
CONTEXT: N6-methyladenosine (m6A) of RNA is involved in the progression of non-small cell lung cancer (NSCLC). OBJECTIVE: This study investigated the role of METTL14 in NSCLC and the mechanism. MATERIALS AND METHODS: Expression levels were assessed by quantitative real-time PCR and ELISA assays. Cells viability was assessed by cell counting kit-8. M6A methylation was analysed by methylated RNA immunoprecipitation (MeRIP), RIP, luciferase assay, and mRNA stability assay. RESULTS: The results showed that METTL14 was highly expressed in NSCLC tissues and cell lines. Knockdown of METTL14 inhibited the cell viability while induced ferroptosis of NSCLC cells. Mechanistically, METTL14 interacts with GPX4, mediates m6A modification of GPX4, enhances its mRNA stability, and upregulates its expression. In addition, IGF2BP1 recognises the m6A-methylated GPX4 and mediates the elevated mRNA stability. Moreover, GPX4 reversed the effects of METTL14 depletion. DISCUSSION AND CONCLUSION: The METTL14/GPX4 axis promotes NSCLC progression by inhibiting cell ferroptosis through the recognition of m6A modification mediated by IGF2BP1.
RESUMO
Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Angiogenesis plays a pivotal role in LUAD progression via supplying oxygen and nutrients for cancer cells. Non-coding miR-1293, a significantly up-regulated miRNA in LUAD tissues, can be potentially used as a novel biomarker for predicting the prognosis of LUAD patients. However, little information is available about the function of miR-1293 in LUAD progression especially cancer-induced angiogenesis. Herein, we found that miR-1293 knockdown could obviously attenuate LUAD-induced angiogenesis in vitro and down-regulate two most important pro-angiogenic cytokines VEGF-A and bFGF expression and secretion. Indeed, miR-1293 abrogation inactivated the angiogenesis-promoting ERK1/2 signaling characterized by decreased ERK1/2 phosphorylation and translocation from nucleus to cytoplasm. Next we found that miR-1293 knockdown reactivated the endogenous ERK1/2 pathway inhibitor Spry4 expression and Spry4 perturbance with specific siRNA transfection abolished the inhibition of ERK1/2 pathway and LUAD-induced angiogenesis by miR-1293 knockdown. Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293.
Assuntos
Adenocarcinoma de Pulmão , Técnicas de Silenciamento de Genes , Neoplasias Pulmonares , Sistema de Sinalização das MAP Quinases , MicroRNAs , Neovascularização Patológica , Regulação para Cima , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animais , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Nus , Masculino , Camundongos Endogâmicos BALB C , Células A549 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Feminino , AngiogêneseRESUMO
Molybdenum (Mo) plays a pivotal role in the growth and nitrogen-fixing process of plants mediated by rhizobia. However, the influence of nanomolybdenum trioxide (MoO3NPs) on soybean growth, rhizosphere bioavailable Mo, and nitrogen-fixing microorganisms remains underexplored. Here, we report that compared with that of ionic Mo and bulk MoO3, the utilization of MoO3NPs (specifically NPs0.05 and NPs0.15) significantly boosted the available Mo content in the rhizosphere soil throughout the seedling (by 21.64 %-101.38 %), podding (by 54.44 %-68.89 %), and mature stage (by 34.41 %-to 45.71 %) of soybean growth. Furthermore, both NPs0.05 and NPs0.15 treatments maintained consistently higher levels of acid-extractable Mo, reducible Mo, and oxidizable Mo across these stages, which facilitated stable conversion and supply of bioavailable Mo. Within the rhizosphere soil, NPs0.05 and NPs0.15 treatments resulted in the highest relative abundance of Rhizobiales and Bradyrhizobium genera, and significantly promoted the colonization of nitrogen-fixing microorganisms, thereby increasing the content of nitrate nitrogen (NO3--N) by 8.69 % and 7.72 % and ammonium nitrogen (NH4+-N) by 44.75 % and 17.55 %, respectively. Ultimately, these effects together contributed to 107.17 % and 84.00 % increment in soybean yield by NPs0.05 and NPs0.15 treatments, respectively. In summary, our findings underscore the potential of employing MoO3NPs to promote plant growth and maintain soil nitrogen cycling, indicating distinct advantages of MoO3NPs over ionic Mo and bulk MoO3.
Assuntos
Glycine max , Molibdênio , Fixação de Nitrogênio , Óxidos , Rizosfera , Microbiologia do Solo , Molibdênio/metabolismo , Solo/químicaRESUMO
Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK + effector memory T cells (Tem) were relatively enriched and CXCL13+ exhausted T cells (Tex) and regulator T cells (Treg) decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B + memory B cells (Bmem) suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK + Tem and TNFRSF13B + Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Terapia Neoadjuvante , Análise de Célula Única , Humanos , Terapia Neoadjuvante/métodos , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Imunoterapia/métodos , Análise de Célula Única/métodos , Feminino , Masculino , Microambiente Tumoral/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Quimiocina CXCL13/genética , Quimiocina CXCL13/metabolismo , Pessoa de Meia-Idade , Idoso , Células T de Memória/imunologia , Células T de Memória/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Antígenos Comuns de Leucócito/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos B/imunologia , Receptores CXCR5/metabolismo , Receptores CXCR5/genéticaRESUMO
Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.