RESUMO
Autophagy represents a fundamental mechanism for maintaining cell survival and tissue homeostasis in response to physiological and pathological stress. Autophagy initiation converges on the FIP200-ATG13-ULK1 complex wherein the serine/threonine kinase ULK1 plays a central role. Here, we reveal that the E3 ubiquitin ligase TRIM27 functions as a negative regulatory component of the FIP200-ATG13-ULK1 complex. TRIM27 directly polyubiquitinates ULK1 at K568 and K571 sites with K48-linked ubiquitin chains, with proteasomal turnover maintaining control over basal ULK1 levels. However, during starvation-induced autophagy, TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1. This cooperative mechanism serves to restrain the amplitude and duration of autophagy. Further evidence from mouse models shows that basal autophagy levels are increased in Trim27 knockout mice and that Trim27 differentially regulates tumorigenesis and metastasis. Our study identifies a key role of STK38L-TRIM27-ULK1 signaling axis in negatively controlling autophagy with relevance established in human breast cancer.
Assuntos
Autofagia , Proteínas Serina-Treonina Quinases , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Carcinogênese/genética , Proteínas de Ligação a DNA , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Proteínas Nucleares , Proteínas Serina-Treonina Quinases/genética , Serina , Fatores de Transcrição , Ubiquitina-Proteína LigasesRESUMO
Early work demonstrated that some two-dimensional (2D) materials could kill bacteria by using their sharp edges to physically rupture the bacteria envelope, which presents distinct advantages over traditional antibiotics, as bacteria are not able to evolve resistance to the former. This mechano-bactericidal mode of action, however, suffers from low antibacterial efficiency, fundamentally because of random orientation of 2D materials outside the bacteria, where the desirable "edge-to-envelope" contacts occur with low probability. Here, we demonstrate a proof-of-concept approach to significantly enhance the potency of the mechano-bactericidal activity of 2D materials. This approach is in marked contrast with previous work, as the 2D materials are designed to be in situ generated inside the bacteria from a molecularly engineered monomer in a self-assembled manner, profoundly promoting the probability of the "edge-to-envelope" contacts. The rationale in this study sheds light on a mechanically new nanostructure-enabled antibacterial strategy to combat antibiotic resistance.
Assuntos
Antibacterianos , Nanoestruturas , Antibacterianos/farmacologia , Antibacterianos/química , Nanoestruturas/química , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Bactérias/efeitos dos fármacosRESUMO
SNHG3, a long noncoding RNA (lncRNA), has been linked to poor outcomes in patients with liver hepatocellular carcinoma (LIHC). In this study, we found that SNHG3 was overexpressed in LIHC and associated with poor outcomes in patients with LIHC. Functional assays, including colony formation, spheroid formation, and in vivo assays showed that SNHG3 promoted stemness of cancer stem cells (CSC) and tumor growth in vivo by interacting with microRNA-502-3p (miR-502-3p). miR-502-3p inhibitor repressed the tumor-suppressing effects of SNHG3 depletion. Finally, by RNA pull-down, dual-luciferase reporter assay, m6A methylation level detection, and m6A-IP-qPCR assays, we found that miR-502-3p targeted YTHDF3 to regulate the translation of integrin alpha-6 (ITGA6) and targeted HBXIP to inhibit the m6A modification of ITGA6 through methyltransferase-like 3 (METTL3). Our study revealed that SNHG3 controls the YTHDF3/ITGA6 and HBXIP/METTL3/ITGA6 pathways by repressing miR-502-3p expression to sustain the self-renewal properties of CSC in LIHC.
Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Integrina alfa6 , Neoplasias Hepáticas , MicroRNAs , Células-Tronco Neoplásicas , RNA Longo não Codificante , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Integrina alfa6/metabolismo , Integrina alfa6/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: 8-Oxoguanine DNA glycosylase (OGG1), a well-known DNA repair enzyme, has been demonstrated to promote lung fibrosis, while the specific regulatory mechanism of OGG1 during pulmonary fibrosis remains unclarified. METHODS: A bleomycin (BLM)-induced mouse pulmonary fibrosis model was established, and TH5487 (the small molecule OGG1 inhibitor) and Mitochondrial division inhibitor 1 (Mdivi-1) were used for administration. Histopathological injury of the lung tissues was assessed. The profibrotic factors and oxidative stress-related factors were examined using the commercial kits. Western blot was used to examine protein expression and immunofluorescence analysis was conducted to assess macrophages polarization and autophagy. The conditional medium from M2 macrophages was harvested and added to HFL-1 cells for culture to simulate the immune microenvironment around fibroblasts during pulmonary fibrosis. Subsequently, the loss- and gain-of function experiments were conducted to further confirm the molecular mechanism of OGG1/PINK1. RESULTS: In BLM-induced pulmonary fibrosis, OGG1 was upregulated while PINK1/Parkin was downregulated. Macrophages were activated and polarized to M2 phenotype. TH5487 administration effectively mitigated pulmonary fibrosis, M2 macrophage polarization, oxidative stress and mitochondrial dysfunction while promoted PINK1/Parkin-mediated mitophagy in lung tissues of BLM-induced mice, which was partly hindered by Mdivi-1. PINK1 overexpression restricted M2 macrophages-induced oxidative stress, mitochondrial dysfunction and mitophagy inactivation in lung fibroblast cells, and OGG1 knockdown could promote PINK1/Parkin expression and alleviate M2 macrophages-induced mitochondrial dysfunction in HFL-1 cells. CONCLUSION: OGG1 inhibition protects against pulmonary fibrosis, which is partly via activating PINK1/Parkin-mediated mitophagy and retarding M2 macrophage polarization, providing a therapeutic target for pulmonary fibrosis.
Assuntos
Bleomicina , DNA Glicosilases , Modelos Animais de Doenças , Macrófagos , Mitofagia , Proteínas Quinases , Fibrose Pulmonar , Animais , Mitofagia/efeitos dos fármacos , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , Camundongos , Macrófagos/metabolismo , Proteínas Quinases/metabolismo , Bleomicina/efeitos adversos , Masculino , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ativação de Macrófagos , Humanos , QuinazolinonasRESUMO
Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.
Assuntos
Desenvolvimento Embrionário/fisiologia , Genoma , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Zigoto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
Easy and effective usage of computational resources is crucial for scientific calculations. Following our recent work of machine-learning (ML) assisted scheduling optimization [J. Comput. Chem. 2023, 44, 1174], we further propose (1) the improved ML models for the better predictions of computational loads, and as such, more elaborate load-balancing calculations can be expected; (2) the idea of coded computation, that is, the integration of gradient coding, in order to introduce fault tolerance during the distributed calculations; and (3) their applications together with re-normalized exciton model with time-dependent density functional theory (REM-TDDFT) for calculating the excited states. Illustrated benchmark calculations include P38 protein, and solvent model with one or several excitable centers. The results show that the improved ML-assisted coded calculations can further improve the load-balancing and cluster utilization, owing primarily profit in fault tolerance that aims at the automated quantum chemical calculations for both ground and excited states.
RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Hepatitis B virus (HBV) is one of the major causes of liver cirrhosis (LC) and HCC. Therefore, the discovery of common markers for hepatitis B or LC and HCC is crucial for the prevention of HCC. METHODS: Expressed genes for to chronic active hepaititis B (CAH-B), LC and HCC were obtained from the GEO and TCGA databases, and co-expressed genes were screened using Protein-protein interaction (PPI) networks, least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine - recursive feature elimination (SVM-RFE). The prognostic value of genes was assessed using Kaplan-Meier (KM) survival curves. Columnar line plots, calibration curves and receiver operating characteristic (ROC) curves of individual genes were used for evaluation. Validation was performed using GEO datasets. The association of these key genes with HCC clinical features was explored using the UALCAN database ( https://ualcan.path.uab.edu/index.html ). RESULTS: Based on WGCNA analysis and TCGA database, the co-expressed genes (565) were screened. Moreover, the five algorithms of MCODE (ClusteringCoefficient, MCC, Degree, MNC, and DMNC) was used to select one of the most important and most closely linked clusters (the top 50 genes ranked). Using, LASSO regression model, RF model and SVM-RFE model, four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) were identified for subsequent research analysis. These 4 genes were highly expressed and associated with poor prognosis and clinical features in HCC patients. CONCLUSION: These four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) may be common biomarkers for CAH-B and HCC or LC and HCC, promising to advance our understanding of the molecular basis of CAH-B/LC/HCC progression.
Assuntos
Carcinoma Hepatocelular , Proteínas de Ciclo Celular , Biologia Computacional , Cinesinas , Cirrose Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Humanos , Cinesinas/genética , Cirrose Hepática/genética , Biologia Computacional/métodos , Proteínas de Ciclo Celular/genética , Prognóstico , Hepatite B Crônica/genética , Hepatite B Crônica/complicações , Biomarcadores Tumorais/genética , Mapas de Interação de Proteínas/genética , Masculino , Estimativa de Kaplan-Meier , Máquina de Vetores de SuporteRESUMO
Sludge is one of the primary reservoirs of microplastics (MPs), and the effects of MPs on subsequent sludge treatment raised attention. Given the entry pathways, MPs would exhibit different properties, but the entry pathway-dependent effect of MPs on sludge treatment performance and the fates of antibiotic resistance genes (ARGs), another high-risk emerging contaminant, were seldom documented. Herein, MPs with two predominant entry pathways, including wastewater-derived (WW-derived) and anaerobic digestion-introduced (AD-introduced), were used to investigate the effects on AD performance and ARGs abundances. The results indicated that WW-derived MPs, namely the MPs accumulated in sludge during the wastewater treatment process, exhibited significant inhibition on methane production by 22.8%-71.6%, while the AD-introduced MPs, being introduced in the sludge AD process, slightly increased the methane yield by 4.7%-17.1%. Meanwhile, MPs were responsible for promoting transmission of target ARGs, and polyethylene terephthalate MPs (PET-MPs) showed a greater promotion effect (0.0154-0.0936) than polyamide MPs (PA-MPs) (0.0013-0.0724). Compared to size, entry pathways and types played more vital roles on MPs influences. Investigation on mechanisms based on microbial community structure revealed characteristics (aging degree and types) of MPs determined the differences of AD performance and ARGs fates. WW-derived MPs with longer aging period and higher aging degree would release toxics and decrease the activities of microorganisms, resulting in the negative impact on AD performance. However, AD-introduced MPs with short aging period exhibited marginal impacts on AD performance. Furthermore, the co-occurrent network analysis suggested that the variations of potential host bacteria induced by MPs with different types and aging degree attributed to the dissemination of ARGs. Distinctively from most previous studies, the MPs with different sizes did not show remarkable effects on AD performance and ARGs fates. Our findings benefited the understanding of realistic environmental behavior and effect of MPs with different sources.
Assuntos
Metano , Microplásticos , Esgotos , Metano/metabolismo , Esgotos/microbiologia , Anaerobiose , Microplásticos/toxicidade , Eliminação de Resíduos Líquidos , Resistência Microbiana a Medicamentos/genética , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Ganoderma lucidum is a medicinal mushroom usually cultivated in logs and covered with soil. Its production decreases after continuous cultivation. Changes of microbial diversity in soil are suggested to be one of the reasons. This study aims to investigate the changes of microbial diversity and abundance in soil during cultivation, and isolate potential microbial strains that affect the yield of G. lucidum. Soil samples were collected at two different ranges from logs during one complete growth cycle of G. lucidum. The changes in fungi and bacteria were investigated by using high-throughput sequencing and real-time PCR. Results indicated that the relative abundance of Firmicutes in the bacterial community decreased at the short-range site. In the fungal community, the relative abundance of Ganoderma increased to 70% at the long-range site at the end of the cultivation. The abundance of bacteria and fungi decreased significantly at the end of the growth cycle. Recovery of microbial changes in soil should be proceeded separately based on different ranges to logs. The microbial strains in these soil samples were also isolated and identified. Potential strains were assessed in the form of bio-fertilizer. The yield of G. lucidum in the field using bio-fertilizer with isolated bacterial strains from the Firmicutes phylum was about 13% higher than that without using bio-fertilizer, suggesting the possibility of alleviating the production decrease of G. lucidum by this method.
Assuntos
Bactérias , Biodiversidade , Fungos , Reishi , Microbiologia do Solo , Reishi/metabolismo , Reishi/crescimento & desenvolvimento , Reishi/genética , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Fungos/metabolismo , Fertilizantes/análise , Microbiota , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Solo/químicaRESUMO
BACKGROUND: Childhood adversities may lead to decreased activity participation in later life, impacting memory health in ageing adults. Childhood adversities related to deprivation and threat, as conceptualized by the Dimensional Model of Adversity, can exhibit distinct impacts on cognitive and emotional outcomes in children and younger adults. This study examined the potential influence of childhood deprivation and threat on memory function in later life and the mediating role of activity participation in these relationships. METHODS: This study used data from the first wave of Panel Study of Active Ageing and Society (PAAS), a representative survey of Hong Kong residents aged 50 or above (N = 1,005). Key variables included late-life memory function measured by delayed recall test, deprivation- and threat-related childhood adversities, and the frequency of participation in informal and formal types of activities. Mediation tests were used for analysis. RESULTS: Childhood deprivation was associated with a lower late-life memory function, whereas threat was not. The negative effects of childhood deprivation and its subdomain, economic hardship, on memory function were mediated by activity participation. Total participation scores presented the strongest mediating effect (17.3-20.6%), with formal activities playing a more substantial mediating role than informal activities in mitigating the effect of childhood deprivation. CONCLUSIONS: These findings expand the applicability of the Dimensional Model of Adversity to ageing populations, highlighting the influence of deprivation on life-long cognitive development. Furthermore, this study revealed an indirect mechanism by which childhood deprivation affects memory health in old age through diverse activity participation.
Assuntos
Experiências Adversas da Infância , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Experiências Adversas da Infância/psicologia , Hong Kong/epidemiologia , Memória/fisiologia , Envelhecimento/psicologia , Envelhecimento/fisiologia , Idoso de 80 Anos ou mais , CriançaRESUMO
We investigated the short- and long-term effects of different forage types supplemented in preweaning dairy calves on growth performance, blood metabolites, rumen fermentation, bacterial community, and milk production during first lactation. A total of 60 healthy 30-d-old female Holstein calves were blocked by birth date and body weight and randomly assigned to 1 of 3 groups (n = 20): normal milk and pelleted starter feeding (CON), supplemented with chopped oat hay (OAH; 75.0 g/d per calf [DM basis]), or alfalfa hay (ALF; 75.0 g/d per calf [DM basis]). The forage supplementation started when calves were 30 d old (d 1 of the experimental period) and ended when they were 73 d old (d 44 of the experimental period, when calves were weaned). Milk and feed intakes and fecal consistency scores were recorded daily. Growth performance, rumen fluid, and blood samples were collected biweekly. After weaning, all the calves were integrated with the same barn and diets. After calving, the milk production was recorded daily. During the experimental period, the OAH group had greater solid feed and total DM intakes and greater rumen pH than the CON group (P ≤ 0.04), but had lower forage intake and CP digestibility than the ALF group (P ≤ 0.04). The ALF group had higher rumen pH and blood BHB concentration (P ≤ 0.04), lower fecal score (P = 0.02), and greater ether extract digestibility (P = 0.02) than the CON group. The ALF and OAH groups had lower concentrations of ruminal total VFA (P = 0.01). Still, the ALF group had a greater proportion of acetate and a relative abundance of cellulose degradation-related bacteria (Lachnoclostridium_1 and Oribacterium) and a lower relative abundance of inflammation-related bacteria (Erysipelotrichaceae_UCG-009) in the rumen compared with CON. Interestingly, the average milk production from 6 to 200 DIM was greater in the ALF group (P < 0.01), even though no significant effects were found on the rumen fermentation parameters and blood metabolites at 200 DIM. Generally, alfalfa hay supplementation in preweaning dairy calves had positive effects in the short- and long-term for rumen development, health status, and future milk production.
Assuntos
Ração Animal , Dieta , Lactação , Leite , Rúmen , Desmame , Animais , Bovinos , Feminino , Leite/metabolismo , Dieta/veterinária , Rúmen/metabolismo , Suplementos Nutricionais , FermentaçãoRESUMO
OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.
Assuntos
Dispepsia , Estimulação do Nervo Vago , Animais , Ratos , Dispepsia/terapia , Fator de Crescimento Neural/metabolismo , Fosfolipase C gama/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , RNA Mensageiro , Transdução de Sinais , Tropomiosina/metabolismoRESUMO
Climate change-induced heat stress (HS) increasingly threatens potato (Solanum tuberosum L.) production by impacting tuberization and causing the premature sprouting of tubers grown during the hot season. However, the effects of post-harvest HS on tuber sprouting have yet to be explored. This study aims to investigate the effects of post-harvest HS on tuber sprouting and to explore the underlying transcriptomic changes in apical bud meristems. The results show that post-harvest HS facilitates potato tuber sprouting and negates apical dominance. A meticulous transcriptomic profiling of apical bud meristems unearthed a spectrum of differentially expressed genes (DEGs) activated in response to HS. During the heightened sprouting activity that occurred at 15-18 days of HS, the pathways associated with starch metabolism, photomorphogenesis, and circadian rhythm were predominantly suppressed, while those governing chromosome organization, steroid biosynthesis, and transcription factors were markedly enhanced. The critical DEGs encompassed the enzymes pivotal for starch metabolism, the genes central to gibberellin and brassinosteroid biosynthesis, and influential developmental transcription factors, such as SHORT VEGETATIVE PHASE, ASYMMETRIC LEAVES 1, SHOOT MERISTEMLESS, and MONOPTEROS. These findings suggest that HS orchestrates tuber sprouting through nuanced alterations in gene expression within the meristematic tissues, specifically influencing chromatin organization, hormonal biosynthesis pathways, and the transcription factors presiding over meristem fate determination. The present study provides novel insights into the intricate molecular mechanisms whereby post-harvest HS influences tuber sprouting. The findings have important implications for developing strategies to mitigate HS-induced tuber sprouting in the context of climate change.
Assuntos
Solanum tuberosum , Solanum tuberosum/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Amido/metabolismo , Tubérculos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Sb2S3 has been extensively used as light absorber for photoelectrochemical cell. However, its p-type nature may result in the formation of Schottky junction with substrates, thus hindering the collection of photogenerated holes. Herein, an ultrathin CuxS layer is successfully engineered as the bottom junction for Sb2S3 for the first time. Capitalizing on its impressive electrical properties and superior optical properties, the CuxS layer exhibits a high work function of 4.90â eV, which causes the upward band bending of p-type Sb2S3, forming a hole-transparent structure with ohmic contact. The transparency of the ultrathin CuxS layer enables back-illumination of the Sb2S3/CuxS platform, facilitating the integration of intricate catalyst layers for photoelectrochemical transformation. When modified with Pt nanoparticles, the photocurrent density reaches -5.38â mA cm-2 at 0â V vs. RHE, marking a fourfold increase compared to the photocathode without CuxS layer. When introducing a molecular hybrid TC-CoPc@carbon black, a remarkable average photocurrent density of -0.44â mA cm-2 at the overpotential of 0â V is obtained for CO2 reduction reaction, while the photocurrent density is less than -0.03â mA cm-2 without CuxS.
RESUMO
BACKGROUND: Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. METHODS: The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). RESULTS: Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. CONCLUSIONS: Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.
RESUMO
Immortalization-upregulated protein (IMUP) plays a vital role in cell proliferation and tumor progression. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we select IMUP as an alternative gene based on GeneChip analysis of clinical PDAC tissues and transcriptome data from The Cancer Genome Atlas. IMUP expression is upregulated in PDAC tumor tissues. Moreover, high IMUP expression correlates with poor prognosis, while IMUP depletion inhibits PDAC cell proliferation and colony formation capacity in vitro, and decreases xenograft tumor growth in vivo. IMUP downregulation leads to cell-cycle arrest in the S phase. IMUP knockdown increases the expression of four-and-a-half LIM domain protein 1 (FHL1), which regulates the phosphorylation of cell division cycle 25A (CDC25A) by cycle checkpoint kinase 1 (CHK1) and promotes cytoplasmic distribution of CDC25A by interaction with 14-3-3ξ. Furthermore, FHL1 knockdown restores the effects induced by IMUP depletion. Liquid chromatography tandem mass spectrometry and immunoprecipitation analysis further show that IMUP interacts directly with nucleophosmin (NPM1) and enhances its stability. DNA methylation sequencing shows that FHL1 promoter methylation decreases when IMUP is downregulated. Overexpression of NPM1 can increase the methylation level of FHL1, thereby decreasing its expression. Our study provides a novel perspective on IMUP/NPM1/FHL1-mediated cell-cycle arrest by regulating CDC25A phosphorylation in PDAC. These findings may provide a new therapeutic target for PDAC.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
For mechanized maize production, a low grain water content (GWC) at harvest is necessary. However, as a complex quantitative trait, understand the genetic mechanism of GWC remains a large gap, especially in hybrids. In this study, a hybrid population through two environments including 442 F1 was used for genome-wide association analysis of GWC and the grain dehydration rate (GDR), using the area under the dry down curve (AUDDC) as the index. Then, we identified 19 and 17 associated SNPs for GWC and AUDDC, including 10 co-localized SNPs, along with 64 and 77 pairs of epistatic SNPs for GWC and AUDDC, respectively. These loci could explain 11.39-68.2% of the total phenotypic variation for GWC and 41.07-67.02% for AUDDC at different stages, whose major effect was the additive and epistatic effect. By exploring the candidate genes around the significant sites, a total of 398 and 457 possible protein-coding genes were screened, including autophagy pathway and auxin regulation-related genes, and five inbred lines with the potential to reduce GWC in the combined F1 hybrid were identified. Our research not only provides a certain reference for the genetic mechanism analysis of GWC in hybrids but also provides an added reference for breeding low-GWC materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01349-x.
RESUMO
Biological tissue usually exhibits good water adaptive mechanical properties, which can maintain high strength and toughness in both wet and dry states. However, synthetic tissue like hydrogel usually becomes hard and brittle in its dry state. Herein, this challenge is met by exploring iron-catechol complex (TA-Fe3+ ) as a great platform combining extremely different polymers (elastomer and hydrogel) to construct new tissue-like soft composite materials with two different continuous phases, which have not yet been reported. In its dry state, the xerogel phase becomes a reinforced segment to increase the strength of PB without losing its toughness. In its wet state, this soft material becomes high performance hydrogel, where hydrogel phase absorbs high water and elastomer phase can sustain high loading. Such heterogeneous phase structures provide a good idea for designing the soft materials, exhibiting a trade-off between its high strength and toughness in both wet and dry states. Furthermore, its shape memory behaviors in both its wet and dry state, which shows a great potential application for complex adaptive shape transformation and engineering application like lifting of heavy objects under remote control due to high photo-thermal transition of TA-Fe3+ is explored.
Assuntos
Elastômeros , Polímeros , Elastômeros/química , Polímeros/química , Hidrogéis/química , Água , EngenhariaRESUMO
A comprehensive and sensitive method combining ultra-performance liquid chromatography with tandem mass spectrometry was developed for the quantification of characteristic triterpenoids in Ganoderma mycelia. Eight ganoderic acids previously isolated from the mycelia of Ganoderma lingzhi were separated with a binary mobile phase on a reversed-phase C18 column. A triple quadrupole mass spectrometer equipped with an electrospray ionization source was used as the detector in the negative ion mode. Identification and quantitation of target ganoderic acids were accomplished using the dynamic multiple reaction monitoring mode. The developed method was validated in terms of linearity, precision, accuracy, stability, and recovery. The method was first applied to quantify the contents of eight ganoderic acids in the mycelia of G. lingzhi at different times to determine the optimum fermentation conditions. Subsequently, the distribution of triterpenoids and the contents of eight ganoderic acids in sixteen different Ganoderma species were investigated. The results indicated that UV chromatography combined with dynamic multiple reaction monitoring quantification was an effective chemotaxonomy method for Ganoderma species identification. This study also provided a helpful analytical methodology for both scientific and industrial applications in the quality control of Ganoderma triterpenoids.
Assuntos
Ganoderma , Triterpenos , Espectrometria de Massas em Tandem , Ganoderma/química , Triterpenos/química , Cromatografia Líquida , Esteroides , Cromatografia Líquida de Alta Pressão/métodosRESUMO
A cationic perylene probe was designed and synthesized for sensitive determination of tartrazine. In the presence of tartrazine, the fluorescence of the perylene probe was quenched by efficient supramolecular self-assembly of the perylene derivate. The quenching is caused by the synergistic effect of noncovalent interactions including static electricity, π-π stacking, and hydrophobic interaction. Benefiting from these advantages, the probe exhibited excellent sensing performance to tartrazine within 2 min. The detection and quantification limit of tartrazine are as low as 2.42 and 8.07 nmol L-1, respectively, with a wide linear operation range from 15 to 500 nmol L-1. Most importantly, due to the high binding affinity (3.22 × 107 mol L-1) between the perylene probe and tartrazine, the sensing system shows great anti-interference capacity. Subsequently, the visualization application of the approach was evaluated by portable device, and the limits of detection for visual detection for test strip, membrane, and hydrogel were 0.5, 0.5, and 5 µmol L-1, respectively. The approach has been applied to monitor tartrazine in various food condiments with recoveries in the range 91.29-108.83%. As far as we know, this is the first report of using perylene-based probe for tartrazine determination, offering a promising strategy for the construction of perylene-based detection system in the field of food safety.