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Aberrantly upregulated choline phospholipid metabolism is a novel emerging hallmark of cancer, and choline kinase α (CHKα), a key enzyme for phosphatidylcholine production, is overexpressed in many types of human cancer through undefined mechanisms. Here, we demonstrate that the expression levels of the glycolytic enzyme enolase-1 (ENO1) are positively correlated with CHKα expression levels in human glioblastoma specimens and that ENO1 tightly governs CHKα expression via posttranslational regulation. Mechanistically, we reveal that both ENO1 and the ubiquitin E3 ligase TRIM25 are associated with CHKα. Highly expressed ENO1 in tumor cells binds to I199/F200 of CHKα, thereby abrogating the interaction between CHKα and TRIM25. This abrogation leads to the inhibition of TRIM25-mediated polyubiquitylation of CHKα at K195, increased stability of CHKα, enhanced choline metabolism in glioblastoma cells, and accelerated brain tumor growth. In addition, the expression levels of both ENO1 and CHKα are associated with poor prognosis in glioblastoma patients. These findings highlight a critical moonlighting function of ENO1 in choline phospholipid metabolism and provide unprecedented insight into the integrated regulation of cancer metabolism by crosstalk between glycolytic and lipidic enzymes.
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Colina , Glioblastoma , Fosfopiruvato Hidratase , Humanos , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Colina/metabolismo , Glioblastoma/genética , Fosfolipídeos/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismoRESUMO
BACKGROUND AND AIMS: Base editing has shown great potential for treating human diseases with mutated genes. However, its potential for treating HCC has not yet been explored. APPROACH AND RESULTS: We employed adenine base editors (ABEs) to correct a telomerase reverse transcriptase ( TERT ) promoter mutation, which frequently occurs in various human cancers, including HCC. The mutated TERT promoter -124 C>T is corrected to -124 C by a single guide (sg) RNA-guided and deactivated Campylobacter jejuni Cas9 (CjCas9)-fused adenine base editor (CjABE). This edit impairs the binding of the E-twenty six/ternary complex factor transcription factor family, including E-twenty six-1 and GABPA, to the TERT promoter, leading to suppressed TERT promoter and telomerase activity, decreased TERT expression and cell proliferation, and increased cell senescence. Importantly, injection of adeno-associated viruses expressing sgRNA-guided CjABE or employment of lipid nanoparticle-mediated delivery of CjABE mRNA and sgRNA inhibits the growth of liver tumors harboring TERT promoter mutations. CONCLUSIONS: These findings demonstrate that a sgRNA-guided CjABE efficiently converts the mutated TERT promoter -124 C>T to -124 C in HCC cells and underscore the potential to treat HCC by the base editing-mediated correction of TERT promoter mutations.
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Organ size is a major agronomic trait that determines grain yield and biomass production in crops. However, the molecular mechanisms controlling organ size, especially in legumes, are poorly understood. Using forward genetic approaches in a Tnt1 insertion mutant population of the model legume Medicago truncatula, we identified SMALL LEAF AND BUSHY1 (SLB1), which is required for the control of organ size and lateral branching. Loss of function of SLB1 led to reduced leaf and flower size but increased lateral branch formation in M. truncatula. SLB1 encodes an F-box protein, an orthologue of Arabidopsis thaliana STERILE APETALA (SAP), that forms part of an SKP1/Cullin/F-box E3 ubiquitin ligase complex. Biochemical and genetic analyses revealed that SLB1 controls M. truncatula organ growth and lateral branching by modulating the stability of BIG SEEDS1 (BS1). Moreover, the overexpression of SLB1 increased seed and leaf size in both M. truncatula and soybean (Glycine max), indicating functional conservation. Our findings revealed a novel mechanism by which SLB1 targets BS1 for degradation to regulate M. truncatula organ size and shoot branching, providing a new genetic tool for increasing seed yield and biomass production in crop and forage legumes.
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Medicago truncatula , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Medicago truncatula/genética , Medicago truncatula/metabolismo , Tamanho do Órgão , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.
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COVID-19/prevenção & controle , Desinfecção/métodos , Reutilização de Equipamento , Máscaras/virologia , Respiradores N95/virologia , Vapor , Gammacoronavirus , Humanos , Pandemias , SARS-CoV-2RESUMO
The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.
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COVID-19/epidemiologia , COVID-19/prevenção & controle , Higiene das Mãos , Equipamento de Proteção Individual , SARS-CoV-2 , COVID-19/transmissão , COVID-19/virologia , Humanos , Respiradores N95 , Pandemias , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/genética , Carga ViralRESUMO
OBJECTIVE: Gastric cancer is one of the most common malignant tumors worldwide, and for resectable tumors, the most effective treatment is surgery with chemotherapy in neoadjuvant or adjuvant setting. However, the majority of patients fail to achieve the ideal initial response and/or develop resistance to chemotherapy. It was reported that long noncoding RNA regulator of reprogramming (ROR) is highly associated with the progression of gastric cancer. However, the role ROR in multidrug resistance (MDR) remains unclear. METHODS: The messenger RNA levels of 63 specimens of patients with gastric cancer were determined by real-time polymerase chain reaction analysis and were correlated with drug resistance and survival of patients. To determine the cellular functions of ROR, we generated gastric cancer MDR cells. The effect of ROR depletion on multidrug resistance-associated protein 1 (MRP1) expression and cell apoptosis were examined by immunoblotting analyses, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry. RESULTS: We found that ROR expression levels are positively associated with increased MDR and poor prognosis of patients with gastric cancer. Regulator of reprogramming expression is increased in gastric cancer cells resistant to adriamycin (ADR) and vincristine (VCR). Depletion of ROR reduced MRP1 expression and increased apoptosis of drug-resistant gastric cancer cells in response to ADR and VCR treatment. CONCLUSIONS: We demonstrated that ROR expression promotes MRP1 expression and MDR of gastric cancer cells and is correlated with increased MDR and poor prognosis of patients with gastric cancer. Our finding highlighted the potential of targeting ROR to improve the efficacy of chemotherapy.
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RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/patologiaRESUMO
The temperature-sensitive and calcium-permeable transient receptor potential vanilloid 3 (TRPV3) channel abundantly expressed in keratinocytes plays important functions in skin physiology. Dysfunctional gain-of-function TRPV3 gene mutations cause genetic Olmsted syndrome characterized by periorificial keratoderma, palmoplantar keratoderma, inflammation, and severe itching, which suggests that pharmacological inhibition of overactive TRPV3 function may be beneficial in treating pruritus or skin disorders. To test this hypothesis, we identified natural compound forsythoside B as a TRPV3 inhibitor through screening of human embryonic kidney 293 (HEK293) cells expressing human TRPV3 channels in a calcium fluorescent assay. Whole-cell patch-clamp recordings of HEK293 cells expressing TRPV3 confirmed that forsythoside B selectively inhibited the channel current activated by agonist 2-aminoethoxydiphenyl borate (50 µM) in a dose-dependent fashion, with an IC50 value of 6.7 ± 0.7 µM. In vivo evaluation of scratching behavior demonstrated that pharmacological inhibition of TRPV3 by forsythoside B significantly attenuated acute itch induced by either the TRPV3 agonist carvacrol or the pruritogen histamine, as well as chronic itch induced by acetone-ether-water in a mouse model of dry skin. Furthermore, forsythoside B was able to prevent the death of HEK293 cells or native human immortalized nontumorigenic keratinocyte cells from human keratinocytes expressing a gain-of-function TRPV3 G573S mutant or in the presence of the TRPV3 agonist carvacrol. Taken together, our findings demonstrate the crucial role of TRPV3 in pruritus and keratinocyte toxicity; thus, specific inhibition of overactive TRPV3 by natural forsythoside B may possess therapeutic potential for treatment of chronic pruritus, skin allergy, or inflammation-related skin diseases.
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Ácidos Cafeicos/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Glucosídeos/uso terapêutico , Queratinócitos/metabolismo , Prurido/tratamento farmacológico , Canais de Cátion TRPV/metabolismo , Animais , Ácidos Cafeicos/farmacologia , Sinalização do Cálcio/fisiologia , Linhagem Celular Transformada , Cimenos , Relação Dose-Resposta a Droga , Glucosídeos/farmacologia , Células HEK293 , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoterpenos/farmacologia , Prurido/metabolismo , Prurido/patologia , Canais de Cátion TRPV/agonistas , TemperaturaRESUMO
YAP, acting as a crucial transcription factor in nucleus, regulates the organ size, tissue homeostasis and tumorigenesis. Dysregulation of Hippo-YAP pathway brings a significant impact on the occurrence and development of various tumor types. Moreover, regulation of YAP/TAZ far exceeds the core kinase of the Hippo pathway, and gradually opens up new therapeutic targets. For the moment, chemotherapy together with radiotherapy act as routine methods to prolong the lives of cancer patients. Seeking more effective anti-neoplastic agents seems to be the urgent problem. This brief review focuses on the research progress of YAP inhibitors as the antineoplastic targets. Small molecule inhibitors or drugs have been discovered including verteporfin, dasatinib, statins, A35, JQ1, norcantharidin, agave, MLN8237, dobutamine and peptide-based YAP inhibitors. We are trying to seek novel therapies from the relationship between known drugs and potential mechanisms.
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Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Fosfoproteínas/antagonistas & inibidores , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
Glioblastoma (GBM), the most common type of primary tumor in the central nervous system, is a very aggressive brain tumor with poor prognosis and a high recurrence rate. Increasing evidence suggests that human cytomegalovirus (HCMV) infection is related to GBM and leads to GBM cell growth and metastasis. MicroRNAs are important regulators in the growth and metastasis of glioblastoma. This study aimed to demonstrate the role of miR-144-3p in HCMV-positive glioblastoma. We found that, after HCMV infection, the expression of miR-144-3p decreased, whereas the expression of TOP2A increased. Bioinformatics analyses indicated that miR-144-3p directly targets the TOP2A 3'-UTR (Untranslated Region). We discovered that the overexpression of miR-144-3p downregulated the overexpression of TOP2A and inhibited the proliferation, clone formation, and invasion of HCMV-positive glioma in vitro. Taken together, these results show that miR-144-3p inhibited growth and promoted apoptosis in glioma cells by targeting TOP2A.
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Neoplasias Encefálicas/patologia , Infecções por Citomegalovirus/genética , DNA Topoisomerases Tipo II/genética , Glioblastoma/patologia , MicroRNAs/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Regiões 3' não Traduzidas , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/virologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/patologia , DNA Topoisomerases Tipo II/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/virologia , Humanos , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/metabolismoRESUMO
Subclinical infection of vaccinated chickens with a highly pathogenic avian influenza A(H5N2) virus was identified through routine surveillance in China. Investigation suggested that the virus has evolved into multiple genotypes. To better control transmission of the virus, we recommend a strengthened program of education, biosecurity, rapid diagnostics, surveillance, and elimination of infected poultry.
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Infecções Assintomáticas , Galinhas/virologia , Vírus da Influenza A/classificação , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Animais , China/epidemiologia , Genótipo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Filogenia , VacinaçãoRESUMO
Despite significant improvements in air quality during and after COVID-19 restrictions, haze continued to occur in Zhengzhou afterwards. This paper compares ionic compositions and sources of PM2.5 before (2019), during (2020), and after (2021) the restrictions to explore the reasons for the haze. The average concentration of PM2.5 decreased by 28.5% in 2020 and 27.9% in 2021, respectively, from 102.49 µg m-3 in 2019. The concentration of secondary inorganic aerosols (SIAs) was 51.87 µg m-3 in 2019, which decreased by 3.1% in 2020 and 12.8% in 2021. In contrast, the contributions of SIAs to PM2.5 increased from 50.61% (2019) to 68.6% (2020) and 61.2% (2021). SIAs contributed significantly to PM2.5 levels in 2020-2021. Despite a 22~62% decline in NOx levels in 2020-2021, the increased O3 caused a similar NO3- concentration (20.69~23.00 µg m-3) in 2020-2021 to that (22.93 µg m-3) in 2019, hindering PM2.5 reduction in Zhengzhou. Six PM2.5 sources, including secondary inorganic aerosols, industrial emissions, coal combustion, biomass burning, soil dust, and traffic emissions, were identified by the positive matrix factorization model in 2019-2021. Compared to 2019, the reduction in PM2.5 from the secondary aerosol source in 2020 and 2021 was small, and the contribution of secondary aerosol to PM2.5 increased by 13.32% in 2020 and 12.94% in 2021. In comparison, the primary emissions, including biomass burning, traffic, and dust, were reduced by 29.71% in 2020 and 27.7% in 2021. The results indicated that the secondary production did not significantly contribute to the PM2.5 decrease during and after the COVID-19 restrictions. Therefore, it is essential to understand the formation of secondary aerosols under high O3 and low precursor gases to mitigate air pollution in the future.
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Cancer cells prefer to utilizing aerobic glycolysis to generate energy and anabolic metabolic intermediates for cell growth. However, whether the activities of glycolytic enzymes can be regulated by specific posttranslational modifications, such as SUMOylation, in response to oncogenic signallings, thereby promoting the Warburg effect, remain largely unclear. Here, we demonstrate that phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key glycolytic enzyme, interacts with SUMO-conjugating enzyme UBC9 and is SUMOylated at K302 in glioblastoma cells. Expression of UBC9, which competitively prevents the binding of ubiquitin E3 ligase APC/C to PFKFB3 and subsequent PFKFB3 polyubiquitination, increases PFKFB3 stability and expression. Importantly, EGFR activation increases the interaction between UBC9 and PFKFB3, leading to increased SUMOylation and expression of PFKFB3. This increase is blocked by inhibition of EGFR-induced AKT activation whereas expression of activate AKT by itself was sufficient to recapitulate EGF-induced effect. Knockout of PFKFB3 expression decreases EGF-enhanced lactate production and GBM cell proliferation and this decrease was fully rescued by reconstituted expression of WT PFKFB3 whereas PFKFB3 K302R mutant expression abrogates EGF- and UBC9-regulated lactate production and GBM cell proliferation. These findings reveal a previously unknown mechanism underlying the regulation of the Warburg effect through the EGFR activation-induced and UBC9-mediated SUMOylation and stabilization of PFKFB3.
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Glioblastoma , Humanos , Glioblastoma/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glicólise , Lactatos/farmacologia , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismoRESUMO
BACKGROUND: Brucellosis, a neglected and global zoonotic disease, infect a variety of mammals, among which sheep are one of the main hosts. This disease results in huge economic losses and is a widespread concern around the world. RESULT: Based on the selection criteria, 40 articles from 2010 to 2021 of five databases (CNKI, Wanfang, VIP, PubMed and Science Direct) reported in America, Africa and Asia were included. The data showed that during this period, the overall seroprevalence of sheep brucellosis on these three continents was 6.2%. At the regional level, sheep brucellosis had the highest seroprevalence (8.5%) in Africa and the lowest seroprevalence (1.9%) in the Americas. With regard to the age of the sheep, the seroprevalence was significantly higher in adult sheep (15.5%) than in lambs (8.6%). Further, the seroprevalence was significantly higher in sheep that had abortion (44.3%) than in pregnant (13.0%) and non-pregnant sheep (9.5%). With regard to herd size, herds with >20 sheep (35.4%) had a significantly higher seroprevalence than herds with <20 sheep (16.8%). In terms of farming and grazing mode, free-range rearing (8.4%) was associated with a significantly higher seroprevalence than intensive farming (2.8%), and mixed grazing (37.0%) was associated with a significantly higher seroprevalence than single grazing (5.7%). CONCLUSION: Sheep brucellosis is widely distributed in sheep-rearing regions of America, Africa and Asia, and sheep are susceptible to brucellosis by themselves or from other infectious sources. Therefore, timely monitoring of ovine brucellosis and improving farming and grazing patterns are critical to reducing the prevalence of brucellosis.
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Brucelose , Doenças das Cabras , Doenças dos Ovinos , Gravidez , Feminino , Animais , Ovinos , Estudos Soroepidemiológicos , Cabras , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/etiologia , Doenças das Cabras/epidemiologia , Brucelose/epidemiologia , Brucelose/veterinária , Fatores de Risco , Ásia , África/epidemiologia , Criação de Animais DomésticosRESUMO
Severe haze occurrence in the north of the North China Plain (NCP) is recognized as a consequence of the regional transport of pollutants initially from the south and then the rapid formation of secondary pollutants in the local air. However, the origin of pollutants causing haze in the southern NCP has not yet been elucidated even through careful data observation. Based on the contents of water-soluble inorganic ions in PM2.5 samples collected during two severe haze episodes in Zhengzhou, a mega city located on the southern edge of the NCP, we estimated the contributions of local primary emissions and secondary pollutants to haze occurrence. On average, Na+, K+, and Ca2+ mainly originated from anthropogenic sources, and their anthropogenic fractions had proportions of 97.5%, 93.9%, and 76.5% in their respective total mass. Anions Cl- and SO42- substantially originated from not only produced substantially via secondary formation but also from primary emissions, and their primary proportions in their respective total mass were 51.1% and 30.8%. In contrast, NH4+ and NO3- were dominated by secondary formation. The increase in PM2.5 was mainly caused by the formation of secondary inorganic (29.1%) and organic species (57.2%) and the primary anthropogenic emissions (12.5%). These results indicated that the haze at the southern edge of the NCP was mainly caused by pollutants in the local areas. Compared to the haze in the northern NCP, the haze in the southern NCP edge had a higher PM2.5 mass concentration and a higher proportion of secondary species, but a lower proportion of primary species, indicating the high heterogeneity of winter haze over the NCP.
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Poluentes Atmosféricos , Poluentes Ambientais , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Íons , Material Particulado/análise , Estações do AnoRESUMO
Haze occurred in Zhengzhou, a megacity in the northern China, with the PM2.5 as high as 254 µg m-3 on 25 December 2019, despite the emergency response measure of restriction on the emission of anthropogenic pollutants which was implemented on December 19 for suppressing local air pollution. Air pollutant concentrations, chemical compositions, and the origins of particulate matter with aerodynamic diameter smaller than 2.5 µm (PM2.5) between 5-26 December were investigated to explore the reasons for the haze occurrence. Results show that the haze was caused by efficient SO2-to-suflate and NOx-to-nitrate conversions under high relative humidity (RH) condition. In comparison with the period before the restriction (5-18 December) when the PM2.5 was low, the concentration of PM2.5 during the haze (19-26 December) was 173 µg m-3 on average with 51% contributed by sulfate (31 µg m-3) and nitrate (57 µg m-3). The conversions of SO2-to-sulfate and NOx-to-nitrate efficiently produced sulfate and nitrate although the concentration of the two precursor gases SO2 and NOx was low. The high RH, which was more than 70% and the consequence of artificial water-vapor spreading in the urban air for reducing air pollutants, was the key factor causing the conversion rates to be enlarged in the constriction period. In addition, the last 48 h movement of the air parcels on 19-26 December was stagnant, and the air mass was from surrounding areas within 200 km, indicating weather conditions favoring the accumulation of locally-originated pollutants. Although emergency response measures were implemented, high gas-to-particle conversions in stagnant and moisture circumstances can still cause severe haze in urban air. Since the artificial water-vapor spreading in the urban air was one of the reasons for the high RH, it is likely that the spreading had unexpected side effects in some certain circumstances and needs to be taken into consideration in future studies.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental/métodos , Nitratos/análise , Óxidos de Nitrogênio/análise , Material Particulado/análise , Estações do Ano , Sulfatos/análise , Água/químicaRESUMO
The formation of secondary aerosol species, including nitrate and sulfate, induces severe haze in the North China Plain. However, despite substantial reductions in anthropogenic pollutants due to severe restriction of residential and industrial activities in 2020 to stop the spread of COVID-19, haze still formed in Zhengzhou. We compared ionic compositions of PM2.5 during the period of the restriction with that immediately before the restriction and in the comparison period in 2019 to investigate the processes that caused the haze. The average concentration of PM2.5 was 83.9 µg m-3 in the restriction period, 241.8 µg m-3 before the restriction, and 94.0 µg m-3 in 2019. Nitrate was the largest contributor to the PM2.5 in all periods, with an average mass fraction of 24%-30%. The average molar concentration of total nitrogen compounds (NOx + nitrate) was 0.89 µmol m-3 in the restriction period, which was much lower than that in the non-restriction periods (1.85-2.74 µmol m-3). In contrast, the concentration of sulfur compounds (SO2 + sulfate) was 0.34-0.39 µmol m-3 in all periods. The conversion rate of NOx to nitrate (NOR) was 0.35 in the restriction period, significantly higher than that before the restriction (0.26) and in 2019 (0.25). NOR was higher with relative humidity in 40-80% in the restriction period than in the other two periods, whereas the conversion rate of SO2 to sulfate did not, indicating nitrate formation was more efficient during the restriction. When O3 occupied more than half of the oxidants (Ox = O3 + NO2), NOR increased rapidly with the ratio of O3 to Ox and was much higher in the daytime than nighttime. Therefore, haze in the restriction period was caused by increased NOx-to-nitrate conversion driven by photochemical reactions.
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Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Humanos , Nitratos/análise , Óxidos de Nitrogênio/análise , Material Particulado/análise , Estações do Ano , Sulfatos/análiseRESUMO
Leptospirosis is an acute infectious disease caused by pathogenic bacteria from the genus Leptospira. The disease is widely distributed throughout China, causing harm to human and animal health. Murine may naturally carry a variety of pathogenic Leptospira, thus being important sources of infection by humans and livestock. The aim of this study was to assess and analyse the prevalence of Leptospira and its risk factors in murine. We collected 46 publications published between inception and 2022 through China Knowledge Network (CNKI), VIP Chinese Journal Database, Wanfang Database, PubMed, and ScienceDirect. In these studies, a total of 54,051 murine in 5 regions of China were investigated, and the prevalence of leptospirosis ranged from 1.11 to 35.29%. The prevalence of murine leptospirosis in south China was the highest, at 20.13%, and the lowest in northeast China, at 1.11% (P < 0.05). The prevalence of leptospirosis in male murine was 21.38%, which was significantly higher than that in females (17.07%; P < 0.05). Results according to detection method subgroup showed that the prevalence from serological testing was 15.94%, which was significantly higher than that of etiology and molecular biology methods (P < 0.01). In the sample subgroup, the positive rate of serum samples was 15.30%, which was significantly higher than that of tissue samples, at 7.97%. In addition, the influence of different geographical factors on prevalence was analyzed, indicating that the Yangtze River Basin was a high-incidence area for leptospirosis. The study showed that Leptospira were ubiquitous throughout the country, and factors such as environment, temperature and landform affect the murine distribution and their bacteria carrying rate. We suggest strengthening the continuous monitoring of leptospirosis and taking effective and comprehensive measures such as reducing water contact, vaccinating in high-incidence seasons, and avoiding human contamination caused by water pollution and contact with infected murine.
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Background: Bovine viral diarrhea is one of the diseases that cause huge economic losses in animal husbandry. Many countries or regions have successively introduced eradication plans, but BVDV still has a high prevalence in the world. This meta-analysis aims to investigate the prevalence and risk factors of BVDV in the world in recent 10 years, and is expected to provide some reference and theoretical basis for BVDV control plans in different regions. Method: Relevant articles published from 2010 to 2021 were mainly retrieved from NCBI, ScienceDirect, Chongqing VIP, Chinese web of knowledge (CNKI), web of science and Wanfang databases. Results: 128 data were used to analyze the prevalence of BVDV from 2010 to 2021. BVDV antigen prevalence rate is 15.74% (95% CI: 11.35-20.68), antibody prevalence rate is 42.77% (95% CI: 37.01-48.63). In the two databases of antigen and antibody, regions, sampling time, samples, detection methods, species, health status, age, sex, breeding mode, and seasonal subgroups were discussed and analyzed, respectively. In the antigen database, the prevalence of dairy cows in the breed subgroup, ELISA in the detection method subgroup, ear tissue in the sample subgroup, and extensive breeding in the breeding mode were the lowest, with significant differences. In the antibody database, the prevalence rate of dairy cows in the breed subgroup and intensive farming was the highest, with a significant difference. The subgroups in the remaining two databases were not significantly different. Conclusion: This meta-analysis determined the prevalence of BVDV in global cattle herds from 2010 to 2021. The prevalence of BVDV varies from region to region, and the situation is still not optimistic. In daily feeding, we should pay attention to the rigorous and comprehensive management to minimize the spread of virus. The government should enforce BVDV prevention and control, implement control or eradication policies according to local conditions, and adjust the policies in time.
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MUC1, a type I transmembrane glycoprotein, mediates tumor growth and cellular differentiation in various types of cancers. However, the mechanism of MUCI in ovarian cancer has not been fully clarified. In our study, we have observed that MUC1 can play a crucial role in the development and progression of ovarian cancer and act as a predictive marker. We also found that MUC1 could increase the expression of EGFR, and MUC1-EGFR co-administration could promote the cellular growth via the AKT pathway. Taxol is an important drug for treating ovarian cancer, which can prevent cancer recurrence and reduce mortality. Our data have collectively reflected that Taxol can prevent ovarian cancer with abnormal expression of MUC1.
Assuntos
Carcinoma Epitelial do Ovário/genética , Regulação Neoplásica da Expressão Gênica , Mucina-1/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Mucina-1/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais/genéticaRESUMO
Plant height is an important agronomic trait that is closely related to biomass yield and crop production. Despite legumes comprise one of the largest monophyletic families that are second only to grasses in terms of economic and nutritional values, due to an ancient genome duplication event, most legume plants have complex genomes, thus the molecular mechanisms that determine plant height are less known in legumes. Here, we report the identification and characterization of MAIN STEM DWARF1 (MSD1), which is required for the plant height in the model legume Medicago truncatula. Loss of function of MSD1 leads to severely reduced main stem height but normal lateral branch elongation in M. truncatula. Histological analysis revealed that the msd1-1 main stem has shorter internodes with reduced cell size and number compared with the wild type, indicating that MSD1 affects cell elongation and cell proliferation. MSD1 encodes a putative GA 20-oxidase that is expressed at significantly higher levels in the main shoot apex than in the lateral shoot apices, suggesting that MSD1 expression is associated with its effect on the main stem elongation. UPLC-MS/MS analysis showed that GA9 and GA4, two identified products of the GA 20-oxidase, were severely reduced in msd1-1, and the dwarf phenotype of msd1-1 could be rescued by supplementation with gibberellic acid GA3, confirming that MSD1 functions as a biologically active GA 20-oxidase. Moreover, we found that disruption of either MtGA20ox7 or MtGA20ox8, homologs of MSD1, has little effects on the elongation of the main stem, while the msd1-1 mtga20ox7-1 mtga20ox8 triple mutants exhibits a severe short main shoot and lateral branches, as well as reduced leaf size, suggesting that MSD1 and its homologs MtGA20ox7 and MtGA20ox8, redundantly regulate M. truncatula shoot elongation and leaf development. Taken together, our findings demonstrate the molecular mechanism of MSD1-mediated regulation of main stem elongation in M. truncatula and provide insights into understanding the functional diversity of GA 20-oxidases in optimizing plant architecture in legumes.