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High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.
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Neoplasias Pulmonares , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Histona Desmetilases/metabolismo , Histonas/metabolismo , Transformação Celular Neoplásica , Neoplasias Pulmonares/genética , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismoRESUMO
Although it is widely accepted that herpesviruses utilize host RNA polymerase II (RNAPII) to transcribe viral genes, the mechanism of utilization varies significantly among herpesviruses. With the exception of herpes simplex virus 1 (HSV-1) in alpha-herpesviruses, the mechanism by which RNAPII transcribes viral genes in the remaining alpha-herpesviruses has not been reported. In this study, we investigated the transcriptional mechanism of an avian alpha-herpesvirus, Anatid herpesvirus 1 (AnHV-1). We discovered for the first time that hexamethylene-bis-acetamide-inducing protein 1 (HEXIM1), a major inhibitor of positive elongation factor B (P-TEFb), was significantly upregulated during AnHV-1 infection, and its expression was dynamically regulated throughout the progression of the disease. However, the expression level of HEXIM1 remained stable before and after HSV-1 infection. Excessive HEXIM1 assists AnHV-1 in progeny virus production, gene expression, and RNA polymerase II recruitment by promoting the formation of more inactive P-TEFb and the loss of RNAPII S2 phosphorylation. Conversely, the expression of some host survival-related genes, such as SOX8, CDK1, MYC, and ID2, was suppressed by HEXIM1 overexpression. Further investigation revealed that the C-terminus of the AnHV-1 US1 gene is responsible for the upregulation of HEXIM1 by activating its promoter but not by interacting with P-TEFb, which is the mechanism adopted by its homologs, HSV-1 ICP22. Additionally, the virus proliferation deficiency caused by US1 deletion during the early infection stage could be partially rescued by HEXIM1 overexpression, suggesting that HEXIM1 is responsible for AnHV-1 gaining transcription advantages when competing with cells. Taken together, this study revealed a novel HEXIM1-dependent AnHV-1 transcription mechanism, which has not been previously reported in herpesvirus or even DNA virus studies.IMPORTANCEHexamethylene-bis-acetamide-inducing protein 1 (HEXIM1) has been identified as an inhibitor of positive transcriptional elongation factor b associated with cancer, AIDS, myocardial hypertrophy, and inflammation. Surprisingly, no previous reports have explored the role of HEXIM1 in herpesvirus transcription. This study reveals a mechanism distinct from the currently known herpesvirus utilization of RNA polymerase II, highlighting the dependence on high HEXIM1 expression, which may be a previously unrecognized facet of the host shutoff manifested by many DNA viruses. Moreover, this discovery expands the significance of HEXIM1 in pathogen infection. It raises intriguing questions about whether other herpesviruses employ similar mechanisms to manipulate HEXIM1 and if this molecular target can be exploited to limit productive replication. Thus, this discovery not only contributes to our understanding of herpesvirus infection regulation but also holds implications for broader research on other herpesviruses, even DNA viruses.
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Anseriformes , Fator B de Elongação Transcricional Positiva , Proteínas de Ligação a RNA , Fatores de Transcrição , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Transcrição Viral , AnimaisRESUMO
The IGF signaling pathway plays critical role in regulating skeletal myogenesis. We have demonstrated that KIF5B, the heavy chain of kinesin-1 motor, promotes myoblast differentiation through regulating IGF-p38MAPK activation. However, the roles of the kinesin light chain (Klc) in IGF pathway and myoblast differentiation remain elusive. In this study, we found that Klc1 was upregulated during muscle regeneration and downregulated in senescence mouse muscles and dystrophic muscles from mdx (X-linked muscular dystrophic) mice. Gain- and loss-of-function experiments further displayed that Klc1 promotes AKT-mTOR activity and positively regulates myogenic differentiation. We further identified that the expression levels of IRS1, the critical node of IGF-1 signaling, are downregulated in Klc1-depleted myoblasts. Coimmunoprecipitation study revealed that IRS1 interacted with the 88-154 amino acid sequence of Klc1 via its PTB domain. Notably, the reduced Klc1 levels were found in senescence and osteoporosis skeletal muscle samples from both mice and human. Taken together, our findings suggested a crucial role of Klc1 in the regulation of IGF-AKT pathway during myogenesis through stabilizing IRS1, which might ultimately influence the development of muscle-related disorders.
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Fator de Crescimento Insulin-Like I , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Proteínas Substratos do Receptor de Insulina/genética , Cinesinas/genética , Camundongos Endogâmicos mdx , Mioblastos , Transdução de SinaisRESUMO
Altruistic punishment is key to establishing cooperation and maintaining social order, yet its developmental trends across cultures remain unclear. Using computational reinforcement learning models, we provided the first evidence of how social feedback dynamically influences group-biased altruistic punishment across cultures and the lifespan. Study 1 (n = 371) found that Chinese participants exhibited higher learning rates than Americans when socially incentivized to punish unfair allocations. Additionally, Chinese adults showed slower learning and less exploration when punishing ingroups than outgroups, a pattern absent in American counterparts, potentially reflecting a tendency towards ingroup favoritism that may contribute to reinforcing collectivist values. Study 2 (n = 430, aged 12-52) further showed that such ingroup favoritism develops with age. Chinese participants' learning rates for ingroup punishment decreased from adolescence into adulthood, while outgroup rates stayed constant, implying a process of cultural learning. Our findings highlight cultural and age-related variations in altruistic punishment learning, with implications for social reinforcement learning and culturally sensitive educational practices promoting fairness and altruism.
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Altruísmo , Punição , Humanos , Punição/psicologia , Adulto , Masculino , Adolescente , Adulto Jovem , Feminino , Pessoa de Meia-Idade , Criança , Reforço Psicológico , Estados Unidos , China , Comparação Transcultural , Biologia Computacional , Aprendizagem/fisiologiaRESUMO
Advanced portable healthcare devices with high efficiencies, small pressure drops, and high-temperature resistance are urgently desired in harsh environments with high temperatures, high humidities, and high levels of atmospheric pollution. Triboelectric nanogenerators (TENGs), which serve as energy converters in a revolutionary self-powered sensor device, present a sustainable solution for meeting these requirements. In this work, we developed a porous negative triboelectric material by synthesizing ZIF-8 on the surface of a cellulose/graphene oxide aerogel, grafting it with trimethoxy(1H,1H,2H,2H-heptadecafluorodecyl)silane, and adding a negative corona treatment, and it was combined with a positive triboelectric material to create a cellulose nanofiber-based TENG self-powered filter. The devices achieved a balance between a small pressure drop (53 Pa) and high filtration efficiency (98.97%, 99.65%, and 99.93% for PM0.3, PM0.5, and PM1, respectively), demonstrating robust filtration properties at high temperatures and high humidities. Our work provides a new approach for developing self-powered wearable healthcare devices with excellent air filtration properties.
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Lung cancer is the leading cause of cancer-related death, with high morbidity and mortality rates due to the lack of reliable methods for diagnosing lung cancer at an early stage. Low-dose computed tomography can help detect abnormal areas in the lungs, but only 16% of cases are diagnosed early. Tests for lung cancer markers are often employed to determine genetic expression or mutations in lung carcinogenesis. Serum glycome analysis is a promising new method for early lung cancer diagnosis as glycopatterns exhibit significant differences in lung cancer patients. In this study, we employed a solid-phase chemoenzymatic method to systematically compare glycopatterns in benign cases, adenocarcinoma before and after surgery, and advanced stages of adenocarcinoma. Our findings indicate that serum high-mannose levels are elevated in both benign cases and adenocarcinoma, while complex N-glycans, including fucose and 2,6-linked sialic acid, are downregulated in the serum. Subsequently, we developed an algorithm that utilizes 16 altered N-glycans, 7 upregulated and 9 downregulated, to generate a score based on their intensity. This score can predict the stages of cancer progression in patients through glycan characterization. This methodology offers a potential means of diagnosing lung cancer through serum glycome analysis.
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Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Polissacarídeos/metabolismo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , FucoseRESUMO
Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.
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Doenças das Cartilagens , Cartilagem Articular , Glucosídeos Iridoides , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Camundongos , Cartilagem Articular/patologia , Microtomografia por Raio-X , Diferenciação Celular , Doenças das Cartilagens/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , CondrogêneseRESUMO
BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.
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Hyperplexing approaches have been aimed to meet the demand for large-scale proteomic analyses. Currently, the analysis capacity has expanded to up to 54 samples within a single experiment by utilizing different isotopic and isobaric reagent combinations. In this report, we propose a super multiplexed approach to enable the analysis of up to 102 samples in a single experiment, by the combination of our recently developed TAG-TMTpro and TAG-IBT16 labeling. We systematically investigated the identification and quantification performance of the 102-plex approach using the mixtures of E. coli and HeLa peptides. Our results revealed that all labeling series demonstrated accurate and reliable quantification performance. The combination of TAG-IBT16 and TAG-TMTpro approaches expands the multiplexing capacity to 102 plexes, providing a more multiplexed quantification method for even larger-scale proteomic analysis. Data are available via ProteomeXchange with the identifier PXD042398.
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Proteoma , Proteômica , Proteoma/análise , Proteômica/métodos , Escherichia coli , Espectrometria de Massas em Tandem/métodos , Peptídeos/análiseRESUMO
Hydrophilic interaction liquid chromatography (HILIC) is widely used for glycopeptide enrichment in shot-gun glycoproteomics to enhance the glycopeptide signal and minimize the ionization competition of peptides. In this work, we have developed a novel hydrophilic material (glycoHILIC) based on glycopeptides and peptides to provide hydrophilic properties. GlycoHILIC was synthesized by oxidizing cotton and then reacting the resulting aldehyde with the N-terminus of the glycopeptide or peptide by reductive amination. Due to the large amount of hydrophilic carbohydrates and hydrophilic amino acids contained in glycopeptides, glycoHILIC showed significantly better enrichment of glycopeptides than cotton itself. Our results demonstrate that glycoHILIC has high selectivity, a low detection limit, and good stability. Over 257 unique N-linked glycosylation sites in 1477 intact N-glycopeptides from 146 glycoproteins were identified from 1 µL of human serum using glycoHILIC. Serum analysis of pancreatic cancer patients found that 38 N-glycopeptides among 21 glycoproteins changed significantly, of which 7 N-glycopeptides increased and 31 N-glycopeptides decreased. These results demonstrate that glycoHILIC can be used for glycopeptide enrichment and analysis.
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Glicopeptídeos , Glicoproteínas , Humanos , Glicopeptídeos/análise , Glicosilação , Cromatografia Líquida/métodos , Interações Hidrofóbicas e HidrofílicasRESUMO
Hydrogels are currently in the limelight for applications in soft electronics but they suffer from the tendency to lose water or freeze when exposed to dry environments or low temperatures. Molecular crowding is a prevalent occurrence in living cells, in which molecular crowding agents modify the hydrogen bonding structure, causing a significant reduction in water activity. Here, a wide-humidity range applicable, anti-freezing, and robust hydrogel is developed through the incorporation of natural amino acid proline (Pro) and conductive MXene into polyvinyl alcohol (PVA) hydrogel networks. Theoretical calculations reveal that Pro can transform "free water" into "locked water" via the molecular-crowding effect, thereby suppressing water evaporation and ice forming. Accordingly, the prepared hydrogel exhibits high water retention capability, with 77% and 55% being preserved after exposure to 20 °C, 28% relative humidity (RH) and 35 °C, 90% RH for 12 h. Meanwhile, Pro lowers the freezing temperature of the hydrogel to 34 °C and enhances its stretchability and strength. Finally, the PVA/Pro/MXene hydrogels are assembled as multifunctional on-skin strain sensors and conductive electrodes to monitor human motions and detect tiny electrophysiological signals. Collectively, this work provides a molecular crowding strategy that will motivate researchers to develop more advanced hydrogels for versatile applications.
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Eletrônica , Congelamento , Umidade , Hidrogéis , Álcool de Polivinil , Hidrogéis/química , Álcool de Polivinil/química , Humanos , Pele , Prolina/químicaRESUMO
Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease.
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OBJECTIVE: Premature peripheral arterial disease (PAD) (age ≤50 years) has been shown to negatively impact the outcomes of lower extremity revascularization (LER). Patients with premature PAD have an increased risk of major amputation compared with older patients. The primary goal of this study is to compare the frequency of reinterventions after LER in patients with premature PAD to their older counterparts with common age of presentation (ie, 60-80 years). METHODS: A retrospective review of consecutive patients undergoing LER for PAD in a single center was performed. Clinical, procedural, and socioeconomic characteristics were compared between patients with premature PAD and the older group. Perioperative and long-term outcomes were captured and compared including mortality, major amputation, reintervention rate and frequency, as well as major adverse limb events. RESULTS: There were 1274 patients who underwent LER (4.3% premature, 61.8% age 60-80). Patients with premature PAD were more likely to be females of racial minorities. Notably, the mean Distressed Communities Index score was significantly higher in the premature PAD group compared with the older patients. Patients with premature PAD were significantly more likely to have end-stage renal disease but less likely to have hypertension, hyperlipidemia, and coronary artery disease compared with older patients. There was no significant difference in perioperative complications. After a mean follow-up of 5 years, patients with premature PAD were significantly more likely to undergo more frequent reinterventions compared with older patients. Kaplan-Meier curves showed similar overall survival and major adverse limb event-free survival between the two groups. CONCLUSIONS: Patients with premature PAD are likely to undergo more frequent reinterventions after initial LER and have similar 5-year survival curves compared with patients at least 20 years older. Demographic and socioeconomic differences impacting patients with premature PAD, even in this relatively underpowered institutional experience, are striking and warrant further investigation.
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AIM: To provide a systematic overview of diabetes risk prediction models used for prediabetes screening to promote primary prevention of diabetes. METHODS: The Cochrane, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for a comprehensive search period of 30 August 30, 2023, and studies involving diabetes prediction models for screening prediabetes risk were included in the search. The Quality Assessment Checklist for Diagnostic Studies (QUADAS-2) tool was used for risk of bias assessment and Stata and R software were used to pool model effect sizes. RESULTS: A total of 29 375 articles were screened, and finally 20 models from 24 studies were included in the systematic review. The most common predictors were age, body mass index, family history of diabetes, history of hypertension, and physical activity. Regarding the indicators of model prediction performance, discrimination and calibration were only reported in 79.2% and 4.2% of studies, respectively, resulting in significant heterogeneity in model prediction results, which may be related to differences between model predictor combinations and lack of important methodological information. CONCLUSIONS: Numerous models are used to predict diabetes, and as there is an association between prediabetes and diabetes, researchers have also used such models for screening the prediabetic population. Although it is a new clinical practice to explore, differences in glycaemic metabolic profiles, potential complications, and methods of intervention between the two populations cannot be ignored, and such differences have led to poor validity and accuracy of the models. Therefore, there is no recommended optimal model, and it is not recommended to use existing models for risk identification in alternative populations; future studies should focus on improving the clinical relevance and predictive performance of existing models.
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Programas de Rastreamento , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/diagnóstico , Medição de Risco , Programas de Rastreamento/métodos , Fatores de Risco , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , FemininoRESUMO
The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells.
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Proteínas de Choque Térmico HSP70 , Vírus da Hepatite do Pato , Sítios Internos de Entrada Ribossomal , Replicação Viral , Vírus da Hepatite do Pato/fisiologia , Vírus da Hepatite do Pato/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Animais , Proteínas Estruturais Virais/metabolismo , Proteínas Estruturais Virais/genética , Patos , Doenças das Aves Domésticas/virologia , Infecções por Picornaviridae/veterinária , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/metabolismo , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Hepatite Viral Animal/virologia , Hepatite Viral Animal/metabolismo , Biossíntese de ProteínasRESUMO
During the replication process, the herpesvirus genome forms the head-to-tail linked concatemeric genome, which is then cleaved and packaged into the capsid. The cleavage and packing process is carried out by the terminase complex, which specifically recognizes and cleaves the concatemeric genome. This process is governed by a cis-acting sequence in the genome, named the a sequence. The a sequence and genome cleavage have been described in some herpesviruses, but it remains unclear in duck plague virus. In this study, we analysed the location, composition, and conservation of a sequence in the duck plague virus genome. The structure of the DPV genome has an a sequence of (DR4)m-(DR2)n-pac1-S termini (32 bp)-L termini (32 bp)-pac2, and the length is 841 bp. Direct repeat (DR) sequences are conserved in different DPV strains, but the number of DR copies is inconsistent. Additionally, the typical DR1 sequence was not found in the DPV a sequence. The Pac1 and pac2 motifs are relatively conserved between DPV and other herpesviruses. Cleavage of the DPV concatemeric genome was detected, and the results showed that the DPV genome can form a concatemer and is cleaved into a monomer at a specific site. We also established a sensitive method, TaqMan dual qRTâPCR, to analyse genome cleavage. The ratio of concatemer to total viral genome was decreased during the replication process. These results will be critical for understanding the process of DPV genome cleavage, and the application of TaqMan dual qRTâPCR will greatly facilitate more in-depth research.
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Patos , Herpesviridae , Animais , Patos/genética , DNA Viral/química , Sequência de Bases , Sequências Repetitivas de Ácido Nucleico , Herpesviridae/genética , Genoma ViralRESUMO
Migratory birds are important vectors for virus transmission, how migratory birds recognize viruses and viruses are sustained in birds is still enigmatic. As an animal model for waterfowl among migratory birds, studying and dissecting the antiviral immunity and viral evasion in duck cells may pave a path to deciphering these puzzles. Here, we studied the mechanism of antiviral autophagy mediated by duck STING in DEF cells. The results collaborated that duck STING could significantly enhance LC3B-II/I turnover, LC3B-EGFP puncta formation, and mCherry/EGFP ratio, indicating that duck STING could induce autophagy. The autophagy induced by duck STING is not affected by shRNA knockdown of ATG5 expression, deletion of the C-terminal tail of STING, or TBK1 inhibitor BX795 treatment, indicating that duck STING activated non-classical selective autophagy is independent of interaction with TBK1, TBK1 phosphorylation, and interferon (IFN) signaling. The STING R235A mutant and Sar1A/B kinase mutant abolished duck STING induced autophagy, suggesting binding with cGAMP and COPII complex mediated transport are the critical prerequisite. Duck STING interacted with LC3B through LIR motifs to induce autophagy, the LIR 4/7 motif mutants of duck STING abolished the interaction with LC3B, and neither activated autophagy nor IFN expression, indicating that duck STING associates with LC3B directed autophagy and dictated innate immunity activation. Finally, we found that duck STING mediated autophagy significantly inhibited duck plague virus (DPV) infection via ubiquitously degraded viral proteins. Our study may shed light on one scenario about the control and evasion of diseases transmitted by migratory birds.
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Autofagia , Patos , Transdução de Sinais , Animais , Mardivirus/fisiologia , Interferons/metabolismo , Alphaherpesvirinae/fisiologia , Imunidade Inata , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologiaRESUMO
High-temperature stress (HS) is a major abiotic stress that affects the yield and quality of plants. Cathepsin B-like protease 2 (CathB2) has been reported to play a role in developmental processes and stress response, but its involvement in HS response has not been identified. Here, overexpression, virus-induced gene silencing (VIGS)and RNA-sequencing analysis were performed to uncover the functional characteristics of SlCathB2-1 and SlCathB2-2 genes for HS response in tomato. The results showed that overexpression of SlCathB2-1 and SlCathB2-2 resulted in reduced heat tolerance of tomato to HS while silencing the genes resulted in enhanced heat tolerance. RNA-sequencing analysis revealed that the heat shock proteins (HSPs) exhibited higher expression in WT than in SlCathB2-1 and SlCathB2-2 overexpression lines. Furthermore, the possible molecular regulation mechanism underlying SlCathB2-1 and SlCathB2-2-mediated response to HS was investigated. We found that SlCathB2-1 and SlCathB2-2 negatively regulated antioxidant capacity by regulating a set of genes involved in antioxidant defence and reactive oxygen species (ROS) signal transduction. We also demonstrated that SlCathB2-1 and SlCathB2-2 positively regulated ER-stress-induced PCD (ERSID) by regulating unfolded protein response (UPR) gene expression. Furthermore, SlCathB2-1 and SlCathB2-2 interacting with proteasome subunit beta type-4 (PBA4) was identified in the ERSID pathway using yeast two-hybrid (Y2H) analysis and bimolecular fluorescence complementation (BiFC) screening. Overall, the study identified both SlCathB2-1 and SlCathB2-2 as new negative regulators to HS and presented a new HS response pathway. This provided the foundation for the construction of heat-tolerant molecular mechanisms and breeding strategies aiming to improve the thermotolerance of tomato plants.
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Solanum lycopersicum , Solanum lycopersicum/genética , Antioxidantes/metabolismo , Temperatura , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA , Resposta ao Choque Térmico/genética , Regulação da Expressão Gênica de PlantasRESUMO
While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.
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Reatores Biológicos , Desnitrificação , Nitrificação , Sulfetos , Sulfetos/química , Processos Autotróficos , Nitritos/metabolismo , Esgotos , Biofilmes , Águas Residuárias/químicaRESUMO
Disparities in socioeconomic status (SES) may affect individuals' risk preferences, which have important developmental consequences across the lifespan. Yet, previous research has shown inconsistent associations between SES and risky decision-making, and little is known about how this link develops from a young age. The current research is among the first to examine how SES influences preschoolers' risky decisions in both gain and loss frames. Across two studies, children aged 5 to 6 years (total N = 309, 154 boys) were asked to choose between certain and risky options. The risky option was more advantageous, equal to, or less advantageous than the certain option. Study 1 revealed that in the loss frame, high-SES children (n = 84, 44 boys) chose more risky options and were more sensitive to the expected value compared to low-SES children (n = 78, 42 boys), especially when the risk was more advantageous. However, this SES difference was not significant in the gain frame. Supporting the potential causal link between SES and risky decision-making, Study 2 further found that experimentally increasing low-SES children's (n = 68, 30 boys) status by providing additional resources increased their risk-seeking behavior in the loss frame. Overall, our findings suggest an interaction between environmental cues (gain vs. loss) and early life circumstances (SES) in shaping children's risk preferences. RESEARCH HIGHLIGHTS: This research is among the first to examine how school backgrounds and experimentally manipulated SES influence preschoolers' risk preferences in gain and loss frames. Children were more risk-seeking for losses than for gains; this framing effect was stronger in higher-SES than lower-SES children. Lower-SES children exhibited fewer risk-seeking behaviors and decreased sensitivity to the expected value of options for losses, but not for gains. A temporary boost in SES increased children's risk-seeking behavior, but not sensitivity to expected values.