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The product of hexokinase (HK) enzymes, glucose-6-phosphate, can be metabolized through glycolysis or directed to alternative metabolic routes, such as the pentose phosphate pathway (PPP) to generate anabolic intermediates. HK1 contains an N-terminal mitochondrial binding domain (MBD), but its physiologic significance remains unclear. To elucidate the effect of HK1 mitochondrial dissociation on cellular metabolism, we generated mice lacking the HK1 MBD (ΔE1HK1). These mice produced a hyper-inflammatory response when challenged with lipopolysaccharide. Additionally, there was decreased glucose flux below the level of GAPDH and increased upstream flux through the PPP. The glycolytic block below GAPDH is mediated by the binding of cytosolic HK1 with S100A8/A9, resulting in GAPDH nitrosylation through iNOS. Additionally, human and mouse macrophages from conditions of low-grade inflammation, such as aging and diabetes, displayed increased cytosolic HK1 and reduced GAPDH activity. Our data indicate that HK1 mitochondrial binding alters glucose metabolism through regulation of GAPDH.
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Glucose , Hexoquinase/metabolismo , Animais , Glucose/metabolismo , Glicólise , Hexoquinase/genética , Camundongos , Mitocôndrias/metabolismo , Via de Pentose FosfatoRESUMO
The interface between the perovskite and electron-transporting material is often treated for defect passivation to improve the photovoltaic performance of devices. A facile 4-Acetamidobenzoic acid (containing an acetamido, a carboxyl, and a benzene ring)-based molecular synergistic passivation (MSP) strategy is developed here to engineer the SnOx /perovskite interface, in which dense SnOx are prepared using an E-beam evaporation technology while the perovskite is deposited with vacuum flash evaporation deposition method. MSP engineering can synergistically passivate defects at the SnOx /perovskite interface by coordinating with Sn4+ and Pb2+ with functional group CO in the acetamido and carboxyl. The optimized solar cell devices can achieve the highest efficiency of 22.51% based on E-Beam deposited SnOx and 23.29% based on solution-processed SnO2 , respectively, accompanied by excellent stability exceeding 3000 h. Further, the self-powered photodetectors exhibit a remarkably low dark current of 5.22 × 10-9 A cm-2 , a response of 0.53 A W-1 at zero bias, a detection limit of 1.3 × 1013 Jones, and a linear dynamic range up to 80.4 dB. This work proposes a molecular synergistic passivation strategy to enhance the efficiency and responsivity of solar cells and self-powered photodetectors.
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BACKGROUND: Ischemic stroke (IS) is a highly prevalent type of stroke with very high rates of disability and death. As the regulatory role of circular RNAs (circRNAs) in various diseases has been revealed, we constructed a stroke cell model to analyze the action mechanism of hsa_circ_0005548 in IS. METHODS: The abundance of hsa_circ_0005548, microRNA-362-3p (miR-362-3p) and E26 transformation specific-1 (ETS-1) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. We constructed an IS cell model in vitro by oxygen-glucose deprivation/reperfusion (OGD/R) treatment and analyzed cell proliferation, apoptosis and inflammatory response through the use of Cell Counting Kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry and Enzyme-linked immunosorbent assay (ELISA), respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed for the analysis of the relationship between miR-362-3p and hsa_circ_0005548 or ETS1. RESULTS: The higher abundance of hsa_circ_0005548 and ETS-1 and lower level of miR-362-3p were observed in human brain microvascular endothelial immortalized (HBMEC-IM) cells under OGD/R. Hsa_circ_0005548 downregulation mitigated OGD/R-induced HBMEC-IM cell injury. Mechanistically, hsa_circ_0005548 targeted miR-362-3p. MiR-362-3p knockdown reversed the effect of hsa_circ_0005548 silencing on OGD/R-induced HBMEC-IM cell injury. ETS1 was validated as a direct target of miR-362-3p, and miR-362-3p attenuated OGD/R-induced HBMEC-IM cell injury by ETS1. Moreover, hsa_circ_0005548 modulated ETS1 via miR-362-3p. CONCLUSION: Hsa_circ_0005548 knockdown repairs OGD/R-induced HBMEC-IM cell damage via miR-362-3p/ETS1 axis.
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BACKGROUND: Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma. CASE PRESENTATION: A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis. CONCLUSIONS: This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.
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Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Cirrose Hepática/sangue , Neoplasias Hepáticas/sangue , Pró-Calcitonina/sangue , Idoso , Infecções Bacterianas/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Doença Hepática Terminal/sangue , Doença Hepática Terminal/patologia , Doença Hepática Terminal/terapia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Sepse/diagnósticoRESUMO
Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp display cardiac dysfunction with iron deficiency, demonstrating that TTP is necessary for maintaining cardiac function in the setting of low cellular iron. Altogether, our results describe a pathway that is activated in iron deficiency to regulate mitochondrial function to match the availability of Fe/S clusters.
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Deficiências de Ferro , Proteínas Ferro-Enxofre/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , NADH Desidrogenase/metabolismo , Tristetraprolina/metabolismo , Animais , Linhagem Celular , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Proteínas Ferro-Enxofre/genética , Camundongos , Camundongos Knockout , Mitocôndrias Cardíacas/enzimologia , NADH Desidrogenase/genética , Oxirredução , Tristetraprolina/genéticaRESUMO
Recent studies suggest that peroxiredoxin1/2 (Prx1/2) may be involved in the pathophysiology of postischemic inflammatory responses in the brain. In this study, we assessed the distribution and function of Prx1/2 in mice after experimental subarachnoid hemorrhage (SAH). We investigated the distribution of Prx1/2 in the brains of mice both in vivo and in vitro using immunofluorescence staining. The expression of Prx1/2 after SAH was determined by Western blot. Adenanthin was used to inhibit Prx1/2 function, and Prx1/2 overexpression was achieved by injecting adeno-associated virus. Oxidative stress and neuronal apoptosis were assessed both in vivo and in vitro. The neurologic function, inflammatory response, and related cellular signals were analyzed. The results showed that Prx1 was mainly expressed in astrocytes, and Prx2 was abundant in neurons. The expression of Prx1/2 was elevated after SAH, and their expression levels peaked before proinflammatory cytokines. Inhibiting Prx1/2 promoted neuronal apoptosis by increasing the hydrogen peroxide (H2O2) levels via the apoptosis signal-regulating kinase 1/p38 pathway. By contrast, overexpression of Prx1/2 attenuated oxidative stress and neuronal apoptosis after SAH. Thus, early expression of Prx1/2 may protect the brain from oxidative damage after SAH and may provide a novel target for treating SAH.-Lu, Y., Zhang, X.-S., Zhou, X.-M., Gao, Y.-Y., Chen, C.-L., Liu, J.-P., Ye, Z.-N., Zhang, Z.-H., Wu, L.-Y., Li, W., Hang, C.-H. Peroxiredoxin 1/2 protects brain against H2O2-induced apoptosis after subarachnoid hemorrhage.
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Apoptose/efeitos dos fármacos , Lesões Encefálicas/prevenção & controle , Encéfalo/fisiologia , Proteínas de Homeodomínio/metabolismo , Peróxido de Hidrogênio/farmacologia , Substâncias Protetoras/farmacologia , Hemorragia Subaracnóidea/fisiopatologia , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Córtex Cerebral , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxidantes/farmacologia , Estresse Oxidativo , Transdução de SinaisRESUMO
BACKGROUND: Magnifying endoscopy with narrow band imaging (M-NBI) has been applied to examine early gastric cancer by observing microvascular architecture and microsurface structure of gastric mucosal lesions. However, the diagnostic efficacy of non-experts in differentiating early gastric cancer from non-cancerous lesions by M-NBI remained far from satisfactory. In this study, we developed a new system based on convolutional neural network (CNN) to analyze gastric mucosal lesions observed by M-NBI. METHODS: A total of 386 images of non-cancerous lesions and 1702 images of early gastric cancer were collected to train and establish a CNN model (Inception-v3). Then a total of 341 endoscopic images (171 non-cancerous lesions and 170 early gastric cancer) were selected to evaluate the diagnostic capabilities of CNN and endoscopists. Primary outcome measures included diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The sensitivity, specificity, and accuracy of CNN system in the diagnosis of early gastric cancer were 91.18%, 90.64%, and 90.91%, respectively. No significant difference was spotted in the specificity and accuracy of diagnosis between CNN and experts. However, the diagnostic sensitivity of CNN was significantly higher than that of the experts. Furthermore, the diagnostic sensitivity, specificity and accuracy of CNN were significantly higher than those of the non-experts. CONCLUSIONS: Our CNN system showed high accuracy, sensitivity and specificity in the diagnosis of early gastric cancer. It is anticipated that more progress will be made in optimization of the CNN diagnostic system and further development of artificial intelligence in the medical field.
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Processamento de Imagem Assistida por Computador/métodos , Imagem de Banda Estreita/métodos , Neoplasias Gástricas/patologia , Detecção Precoce de Câncer/métodos , Mucosa Gástrica/patologia , Humanos , Redes Neurais de Computação , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.
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Coma/complicações , Mesencéfalo/diagnóstico por imagem , Nocardiose/complicações , Nocardiose/diagnóstico , Nocardia/isolamento & purificação , Tálamo/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Ciclofosfamida/efeitos adversos , Diagnóstico Diferencial , Drenagem , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Mesencéfalo/patologia , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Tálamo/patologia , Tomógrafos Computadorizados , Resultado do TratamentoRESUMO
BACKGROUND: Immune inhibitory receptors play an important role in chronic infections. However, little is known about their role in hepatitis B virus (HBV) infection. Here, we analyzed the relationship between programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) expression on CD4+ T cells and HBV disease progression. RESULTS: PD-1 and LAG-3 expression was significantly higher on CD4+ T cells from HBV patients than on those from the HCs. In addition, a significant positive correlation was found between the PD-1 and LAG-3 expression levels and the ALT(alanine aminotransferase) level. CD4+ T cell function was inhibited by high PD-1 and LAG-3 levels, and CD4+ T cells with high PD-1 and LAG-3 expression lost the ability to secrete IFN-γ, IL-2 and TNF-α. Furthermore, blockade of the PD-1 and LAG-3 pathways reversed the damage to CD4+ T cell proliferation and cytokine secretion. CONCLUSIONS: CD4+ T cell exhaustion during chronic HBV had high PD-1 and LAG-3 expression and the absence of helper T cell cytokines, including IFN-γ, IL-2 and TNF-α. After blocking PD-L1 and LAG-3, CD4+ T cell function in chronic hepatitis B patients was partially restored.
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Antígenos CD/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Receptor de Morte Celular Programada 1/genética , Adulto , Antígenos CD/metabolismo , Antineoplásicos Imunológicos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Testes de Função Hepática , Ativação Linfocitária , Masculino , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Carga Viral , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
BACKGROUND: Microglia are resident immune cells in the central nervous system and central to the innate immune system. Excessive activation of microglia after subarachnoid haemorrhage (SAH) contributes greatly to early brain injury, which is responsible for poor outcomes. Dehydroepiandrosterone (DHEA), a steroid hormone enriched in the brain, has recently been found to regulate microglial activation. The purpose of this study was to address the role of DHEA in SAH. METHODS: We used in vivo models of endovascular perforation and in vitro models of haemoglobin exposure to illustrate the effects of DHEA on microglia in SAH. RESULTS: In experimental SAH mice, exogenous DHEA administration increased DHEA levels in the brain and modulated microglial activation. Ameliorated neuronal damage and improved neurological outcomes were also observed in the SAH mice pretreated with DHEA, suggesting neuronal protective effects of DHEA. In cultured microglia, DHEA elevated the mRNA and protein levels of Jumonji d3 (JMJD3, histone 3 demethylase) after haemoglobin exposure, downregulated the H3K27me3 level, and inhibited the transcription of proinflammatory genes. The devastating proinflammatory microglia-mediated effects on primary neurons were also attenuated by DHEA; however, specific inhibition of JMJD3 abolished the protective effects of DHEA. We next verified that DHEA-induced JMJD3 expression, at least in part, through the tropomyosin-related kinase A (TrkA)/Akt signalling pathway. CONCLUSIONS: DHEA has a neuroprotective effect after SAH. Moreover, DHEA increases microglial JMJD3 expression to regulate proinflammatory/anti-inflammatory microglial activation after haemoglobin exposure, thereby suppressing inflammation.
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Desidroepiandrosterona/farmacologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Hemorragia Subaracnóidea/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The growth of oocytes and the development of follicles require certain pathways involved in cell proliferation and survival, such as the phosphatidylinositol 3-kinase (PI3K) pathway and the Notch signalling pathway. The aim of the present study was to investigate the interaction between Notch and the PI3K/AKT signalling pathways and their effects on primordial follicle recruitment. When the Notch pathway was inhibited by L-685,458 or N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT) in vitro, the expression of genes in the pathway and the percentage of oocytes in growing follicles decreased significantly in mouse ovaries. By 2 days postpartum, ovaries exposed to DAPT, short interference (si) RNA against Notch1 or siRNA against Hairy and enhancer of split-1 (Hes1) had significantly decreased expression of HES1, the target protein of the Notch signalling pathway. In contrast, expression of phosphatase and tensin homologue (Pten), a negative regulator of the AKT signalling pathway, was increased significantly. Co immunoprecipitation (Co-IP) revealed an interaction between HES1 and PTEN. In addition, inhibition of the Notch signalling pathway suppressed AKT phosphorylation and the proliferation of granulosa cells. In conclusion, the recruitment of primordial follicles was affected by the proliferation of granulosa cells and regulation of the interaction between the Notch and PI3K/AKT signalling pathways.
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Regulação da Expressão Gênica no Desenvolvimento , Oogênese , Folículo Ovariano/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Animais , Comunicação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Células da Granulosa/citologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Camundongos , Oogênese/efeitos dos fármacos , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Técnicas de Cultura de Tecidos , Fatores de Transcrição HES-1/antagonistas & inibidores , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
BACKGROUND: Selective prophylactic decontamination of the digestive tract is a strategy for the prevention of secondary nosocomial infection in patients with avian influenza virus subtype H7N9 infection. Our aim was to summarize the effectiveness of these therapies in re-establishing a stable and diverse microbial community, and reducing secondary infections. METHODS: Comprehensive therapies were dependent on the individual clinical situation of subjects, and were divided into antiviral treatment, microbiota-targeted therapies, including pro- or pre-biotics and antibiotic usage, and immunotherapy. Quantitative polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE) were used for real-time monitoring of the predominant intestinal microbiome during treatment. Clinical information about secondary infection was confirmed by analyzing pathogens isolated from clinical specimens. RESULTS: Different antibiotics had similar effects on the gut microbiome, with a marked decrease and slow recovery of the Bifidobacterium population. Interestingly, most fecal microbial DGGE profiles showed the relative stability of communities under the continual suppression of the same antibiotics, and significant changes when new antibiotics were introduced. Moreover, we found no marked increase in C-reactive protein, and no cases of bacteremia or pneumonia, caused by probiotic use in the patients, which confirmed that the probiotics used in this study were safe for use in patients with H7N9 infection. Approximately 72% of those who subsequently suffered exogenous respiratory infection by Candida species or multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae were older than 60 years. The combination of probiotics and prebiotics with antibiotics seemed to fail in these patients. CONCLUSIONS: Elderly patients infected with the influenza A (H7N9) virus are considered a high-risk group for developing secondary bacterial infection. Microbiota restoration treatment reduced the incidence of enterogenous secondary infection, but not exogenous respiratory infection. The prophylactic effects of microbiota restoration strategies for secondary infection were unsatisfactory in elderly and critically ill patients.
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Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Bifidobacterium , China/epidemiologia , Feminino , Humanos , Imunoterapia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Probióticos/uso terapêuticoRESUMO
Notch signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms. The objective of this study was to examine Notch signaling pathway in germ cell cyst breakdown and primordial follicle formation. The receptor and ligand genes of Notch pathway (Notch1, Notch2, Jagged1, Jagged2 and Hes1) were extremely down-regulated after newborn mouse ovaries were cultured then exposed to DAPT or L-685,458 in vitro (P < 0.01). Since DAPT or L-685,548 inhibits Notch signaling pathway, the expression of protein LHX8 and NOBOX was significantly reduced during the formation of the primordial follicles. Down-regulated mRNA expression of specific genes including Lhx8, Figla, Sohlh2 and Nobox, were also observed. The percentages of female germ cells in germ cell cysts and primordial follicles were counted after culture of newborn ovaries for 3 days in vitro. The result showed female germ cells in cysts was remarkably up-regulated while as the oocytes in primordial follicles was significantly down-regulated (P < 0.05). In conclusion, Notch signaling pathway may regulate the formation of primordial follicle in mice.
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Células Germinativas/metabolismo , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Animais , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Sobrevivência Celular/genética , Feminino , Células Germinativas/crescimento & desenvolvimento , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteína Jagged-1 , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Oócitos/crescimento & desenvolvimento , Folículo Ovariano/crescimento & desenvolvimento , Receptor Notch1/biossíntese , Receptor Notch1/genética , Receptor Notch2/biossíntese , Receptor Notch2/genética , Proteínas Serrate-Jagged , Transdução de Sinais/genética , Fatores de Transcrição HES-1RESUMO
A total of 13 surface sediments were collected from Hangzhou Bay (HZB) for an investigation into the distribution and influencing factors of anammox bacterial community. The anammox bacterial 16S rRNA and hzo genes ranged between 2.34 × 105 to 9.22 × 105 copies/g and 3.68 × 105 to 1.70 × 106 copies/g, respectively. The results of high throughput sequencing (HTS) revealed that the obtained OTUs were affiliated with five known genera, named Ca. Scalindua, Ca. Jettenia, Ca. Brocadia, Ca. Kuenenia and Ca. Anammoxoglobus. RDA analysis indicated that salinity, pH, and water depth influenced the anammox bacterial community. Furthermore, network analysis identified Ca. Scalindua as a key genus. Neutral community model (NCM) and modified stochasticity ratio (MST) indicated that the deterministic process dominated the anammox bacterial community assembly. Overall, this study offers a more comprehensive understanding of the abundance and community of anammox bacteria in the sediments of HZB.
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Compostos de Amônio , Oxidação Anaeróbia da Amônia , RNA Ribossômico 16S/genética , Baías , Sedimentos Geológicos/microbiologia , Oxirredução , Bactérias/genética , China , FilogeniaRESUMO
Cold seep sediments are an important reservoir of microplastics (MPs) whose impact on the structure and function of prokaryotic community is not well understood. In this study, the impact of 0.2% and 1% (w/w) polyethylene (PE), polystyrene (PS), and polypropylene (PP) MPs on the cold seep sediment prokaryotic community was investigated in a 120-day laboratory incubation experiment. The results revealed that exposure to MPs altered sedimentary chemical properties in a type- and concentration-dependent manner. Furthermore, MPs significantly altered the structure of bacterial community, with some MPs degradation-associated bacterial phyla significantly increasing (p < 0.05). However, in the case of archaea, the changes in the structure of microbial community were less pronounced (p > 0.05). Co-occurrence network analysis revealed that the addition of MPs reduced the network complexity, while PICRUSt2 and FAPROTAX analyses suggested that 0.2% PP and 1% PS MPs had the most significant effects on the nitrogen and carbon cycles (p < 0.05). Overall, this study provides new insights into the effects of MPs on the structure and function of microbial communities in cold seep sediments.
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Microplásticos , Plásticos , Bactérias , Archaea , Polipropilenos , PoliestirenosRESUMO
Several studies reported that the presence of microplastics (MPs)/nanoplastics (NPs) in marine environments can alter microbial community and function. Yet, the impact of aged MPs/NPs on deep sea sedimentary ecosystems under high hydrostatic pressure remains insufficiently explored. Herein, the sedimentary microbial community composition, co-occurrence network, assembly, and transfer of antibiotic resistance genes (ARGs) in response to aged MPs/NPs were investigated. Compared with the control, NPs addition significantly reduced bacterial alpha diversity (p < 0.05), whereas MPs showed no significant impact (p > 0.05). Moreover, networks under NPs exhibited decreased complexity than that under MPs and the control, including edges, average degree, and the number of keystone. The assembly of the microbial community was primarily governed by stochastic processes, and aged MPs/NPs increased the importance of stochastic processes. Moreover, exposure to MPs/NPs for one month decreased the abundance of antibiotic resistance genes (ARGs) (from 94.8 to 36.2 TPM), while exposure for four months increased the abundance (from 40.6 to 88.1 TPM), and the shift of ARGs in sediment was driven by both functional modules and microbial community. This study is crucial for understanding the stress imposed by aged MPs/NPs on sedimentary ecosystems under high hydrostatic pressure.
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Soil desertification is an important challenge in global soil management, and effectively and stably restoring soil function is an urgent problem. Using synthetic microbial communities (SynComs) is a burgeoning microbial strategy aimed at enhancing soil nutrients through functional synergies among diverse microorganisms; nevertheless, their effectiveness in restoring desertified soils remains unknown. In this study, we conducted a two-year field experiment using a SynCom constructed by in situ probiotic bacteria and set up control, chemical fertilizer, and combined SynCom-chemical fertilizer (combined fertilizer) treatments to investigate the linkage between microbial communities and soil multifunctionality in the soil surface layer (0-10 cm). Both the bacterial and fungal communities differed the most under the combined fertilizer treatment compared to the control. The bacterial communities differed more under treatments of the SynCom than the chemical fertilizer, while the fungal communities differed more under the chemical fertilizer treatment than the SynCom treatment. Regarding soil function, the SynCom strengthened the correlation between enzyme activities and both bacterial communities and functional properties. pH and available potassium were the main influencing factors under the chemical fertilizer and combined fertilizer treatments. The beta-diversity of the bacterial communities was significantly correlated with soil multifunctionality. Random forest analyses showed that the SynCom significantly enhanced the bacterial communities, driving soil multifunctionality, and that some potential microbial taxa drove multiple nutrient cycles simultaneously. In summary, the SynCom effectively increased the abundance of most carbon, nitrogen, and phosphorus functional genes as well as soil enzyme activities. The bacterial community composition contributed significantly to soil multifunctionality. Hence, the development of novel microbial agents holds significant potential for improving soil functionality and managing desertification.
RESUMO
Accurate fruit detection is crucial for automated fruit picking. However, real-world scenarios, influenced by complex environmental factors such as illumination variations, occlusion, and overlap, pose significant challenges to accurate fruit detection. These challenges subsequently impact the commercialization of fruit harvesting robots. A tomato detection model named YOLO-SwinTF, based on YOLOv7, is proposed to address these challenges. Integrating Swin Transformer (ST) blocks into the backbone network enables the model to capture global information by modeling long-range visual dependencies. Trident Pyramid Networks (TPN) are introduced to overcome the limitations of PANet's focus on communication-based processing. TPN incorporates multiple self-processing (SP) modules within existing top-down and bottom-up architectures, allowing feature maps to generate new findings for communication. In addition, Focaler-IoU is introduced to reconstruct the original intersection-over-union (IoU) loss to allow the loss function to adjust its focus based on the distribution of difficult and easy samples. The proposed model is evaluated on a tomato dataset, and the experimental results demonstrated that the proposed model's detection recall, precision, F1 score, and AP reach 96.27%, 96.17%, 96.22%, and 98.67%, respectively. These represent improvements of 1.64%, 0.92%, 1.28%, and 0.88% compared to the original YOLOv7 model. When compared to other state-of-the-art detection methods, this approach achieves superior performance in terms of accuracy while maintaining comparable detection speed. In addition, the proposed model exhibits strong robustness under various lighting and occlusion conditions, demonstrating its significant potential in tomato detection.
RESUMO
Heart failure with preserved ejection fraction (HFpEF) is commonly found in persons living with HIV (PLWH) even when antiretroviral therapy suppresses HIV viremia. However, studying this condition has been challenging because an appropriate animal model is not available. In this article, we studied calcium transient in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in culture to simulate the cardiomyocyte relaxation defect noted in PLWH and HFpEF and assess whether various drugs have an effect. We show that treatment of hiPSC-CMs with inflammatory cytokines (such as interferon-γ or TNF-α) impairs their Ca2+ uptake into sarcoplasmic reticulum and that SGLT2 inhibitors, clinically proven as effective for HFpEF, reverse this effect. Additionally, treatment with mitochondrial antioxidants (like mito-Tempo) and certain antiretrovirals resulted in the reversal of the effects of these cytokines on calcium transient. Finally, incubation of hiPSC-CMs with serum from HIV patients with and without diastolic dysfunction did not alter their Ca2+-decay time, indicating that the exposure to the serum of these patients is not sufficient to induce the decrease in Ca2+ uptake in vitro. Together, our results indicate that hiPSC-CMs can be used as a model to study molecular mechanisms of inflammation-mediated abnormal cardiomyocyte relaxation and screen for potential new interventions.
Assuntos
Cálcio , Células-Tronco Pluripotentes Induzidas , Inflamação , Miócitos Cardíacos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Infecções por HIV/metabolismo , Insuficiência Cardíaca/metabolismo , Células CultivadasRESUMO
Polyhalogenated carbazoles (PHCZs), an emerging persistent halogenated organic pollutant, have been detected in the environment. However, our understanding of PHCZs in the ocean remains limited. In this study, 47 seawater samples (covering 50 - 4000 m) and sediment samples (49 surface and 3 cores) were collected to investigate the occurrence and spatial distribution patterns of carbazole and its halogenated derivants (CZDs) in the Western Pacific Ocean. In seawater, the detection frequencies of CZ (97.87%) and 3-CCZ (57.45%) were relatively high. In addition, the average concentration of ΣPHCZs in the upper water (< 150 m, 0.23 ± 0.21 ng/L) was significantly lower than that in the deep ocean (1000 - 4000 m, 0.65 ± 0.56 ng/L, P < 0.05), which may indicate the vertical transport of PHCZs in the marine environment. The concentration of ΣCZDs in surface sediment ranges from 0.46 to 6.48 ng/g (mean 1.54 ng/g), among which CZ and 36-CCZ were the predominant components. Results from sediment cores demonstrate a noteworthy negative correlation between the concentration of CZDs and depth, indicating the ongoing natural degradation process occurring in sediment cores over a long period. This study offers distinctive insights into the occurrence, composition, and vertical features of CZDs in oceanic environments.