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1.
Cell ; 163(2): 313-23, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26435105

RESUMO

In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that "explain" patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system.


Assuntos
Camundongos , Atrativos Sexuais/urina , Órgão Vomeronasal/fisiologia , Animais , Cromatografia Líquida , Feminino , Masculino , Camundongos Endogâmicos , Neurônios/citologia , Neurônios/fisiologia , Atrativos Sexuais/química , Comportamento Sexual Animal , Olfato , Especificidade da Espécie , Espectrometria de Massas em Tandem
2.
Plant Cell ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801738

RESUMO

Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.

3.
Trends Immunol ; 44(12): 1031-1045, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37932176

RESUMO

Tumor immunotherapy is refashioning traditional treatments in the clinic for certain tumors, especially by relying on the activation of T cells. However, the safety and effectiveness of many antitumor immunotherapeutic agents are suboptimal due to difficulties encountered in assessing T cell responses and adjusting treatment regimens accordingly. Here, we review advances in the clinical visualization of T cell activity in vivo, and focus particularly on molecular imaging probes and biomarkers of T cell activation. Current challenges and prospects are also discussed that aim to achieve a better strategy for real-time monitoring of T cell activity, predicting prognoses and responses to tumor immunotherapy, and assessing disease management.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Linfócitos T , Neoplasias/terapia , Imunoterapia/métodos , Imagem Molecular
4.
J Virol ; 98(1): e0165423, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38169290

RESUMO

Jeilongviruses are emerging single-stranded negative-sense RNA viruses in the Paramyxoviridae family. Tailam paramyxovirus (TlmPV) is a Jeilongvirus that was identified in 2011. Very little is known about the mechanisms that regulate viral replication in these newly emerging viruses. Among the non-structural viral proteins of TlmPV, the C protein is predicted to be translated from an open reading frame within the phosphoprotein gene through alternative translation initiation. Though the regulatory roles of C proteins in virus replication of other paramyxoviruses have been reported before, the function of the TlmPV C protein and the relevant molecular mechanisms have not been reported. Here, we show that the C protein is expressed in TlmPV-infected cells and negatively modulates viral RNA replication. The TlmPV C protein interacts with the P protein, negatively impacting the interaction between N and P, resulting in inhibition of viral RNA replication. Deletion mutagenesis studies indicate that the 50 amino-terminal amino acid residues of the C protein are dispensable for its inhibition of virus RNA replication and interaction with the P protein.IMPORTANCETailam paramyxovirus (TlmPV) is a newly identified paramyxovirus belonging to the Jeilongvirus genus, of which little is known. In this work, we confirmed the expression of the C protein in TlmPV-infected cells, assessed its function, and defined a potential mechanism of action. This is the first time that the existence of a Jeilongvirus C protein has been confirmed and its role in viral replication has been reported.


Assuntos
Paramyxovirinae , Proteínas Virais , Replicação Viral , Paramyxovirinae/genética , Paramyxovirinae/fisiologia , RNA Viral/genética , Proteínas Virais/genética , Animais , Cricetinae , Linhagem Celular
5.
Infect Immun ; 92(1): e0022923, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38099659

RESUMO

Legionella is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires' disease, with fever and pneumonia as the main symptoms. The emergence of highly virulent and azithromycin-resistant Legionella pneumophila is a major challenge in clinical anti-infective therapy. The CRISPR-Cas acquired immune system provides immune defense against foreign nucleic acids and regulates strain biological functions. However, the distribution of the CRISPR-Cas system in Legionella and how it regulates gene expression in L. pneumophila remain unclear. Herein, we assessed 915 Legionella whole-genome sequences to determine the distribution characteristics of the CRISPR-Cas system and constructed gene deletion mutants to explore the regulation of the system based on growth ability in vitro, antibiotic sensitivity, and intracellular proliferation of L. pneumophila. The CRISPR-Cas system in Legionella was predominantly Type II-B and was mainly concentrated in the genome of L. pneumophila ST1 strains. The Type II-B CRISPR-Cas system showed no effect on the strain's growth ability in vitro but significantly reduced resistance to azithromycin and decreased proliferation ability due to regulation of the lpeAB efflux pump and the Dot/Icm type IV secretion system. Thus, the Type II-B CRISPR-Cas system plays a crucial role in regulating the virulence of L. pneumophila. This expands our understanding of drug resistance and pathogenicity in Legionella, provides a scientific basis for the prevention of Legionnaires' disease outbreaks and the rational use of clinical drugs, and facilitates effective treatment of Legionnaires' disease.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Humanos , Doença dos Legionários/microbiologia , Azitromicina/farmacologia , Sistemas CRISPR-Cas , Legionella pneumophila/genética
6.
Stroke ; 55(1): 156-165, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38037225

RESUMO

BACKGROUND: Stroke survivors with impaired balance and motor function tend to have relatively poor functional outcomes. The cerebellum and primary motor cortex (M1) have been suggested as targets for neuromodulation of balance and motor recovery after stroke. This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor recovery in patients with stroke. METHODS: In this randomized, double-blind, sham-controlled clinical trial, patients with subacute stroke were randomly divided into 3 groups: M1-, cerebellar-, and sham-iTBS (n=12 per group; 15 sessions, 3 weeks). All outcomes were evaluated before intervention (T0), after 1 week of intervention (T1), after 3 weeks of intervention (T2), and at follow-up (T3). The primary outcome was the Berg balance scale score at T2. Secondary outcomes include the Fugl-Meyer assessment scale for lower extremities, the trunk impairment scale, the Barthel index, the modified Rankin Scale, the functional ambulation categories, and cortical excitability. RESULTS: A total of 167 inpatients were screened, 36 patients (age, 57.50±2.41 years; 10 women, 12 ischemic) were enrolled between December 2020 and January 2023. At T2, M1- or cerebellar-iTBS significantly improved Berg balance scale scores by 10.7 points ([95% CI, 2.7-18.6], P=0.009) and 14.2 points ([95% CI, 1.2-27.2], P=0.032) compared with the sham-iTBS group. Moreover, the cerebellar-iTBS group showed a significantly greater improvement in Fugl-Meyer assessment scale for lower extremities scores by 5.6 points than the M1-iTBS ([95% CI, 0.3-10.9], P=0.037) and by 7.8 points than the sham-iTBS ([95% CI, 1.1-14.5], P=0.021) groups at T2. The motor-evoked potential amplitudes of the M1- and cerebellar-iTBS groups were higher than those of the sham-iTBS group (P<0.001). CONCLUSIONS: Both M1- and cerebellar-iTBS could improve balance function. Moreover, cerebellar-iTBS, but not M1-iTBS, induced significant effects on motor recovery. Thus, cerebellar-iTBS may be a valuable new therapeutic option in stroke rehabilitation programs. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2100047002.


Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana , Cerebelo
7.
Biochem Biophys Res Commun ; 690: 149248, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37992526

RESUMO

Allelochemicals are specific secondary metabolites that can exhibit autotoxicity by inhibiting the growth of the same plant species that produced them. These metabolites have been found to affect various physical processes during plant growth and development, including inhibition of seed germination, photosynthesis, respiration, root growth, and nutrient uptake, with diverse mechanisms involving cell destruction, oxidative homeostasis and photoinhibition. In some cases, allelochemicals can also have positive effects on plant growth and development. In addition to their ecological significance, allelochemicals also possess potential as plant growth regulators (PGRs) due to their extensive physiological effects. However, a comprehensive summary of the development and applications of allelochemicals as PGRs is currently lacking. In this review, we present an overview of the sources and categories of allelochemicals, discuss their effects and the underlying mechanisms on plant growth and development. We showcase numerous instances of key phytohormonal allelochemicals and non-phytohormonal allelochemicals, highlighting their potential as candidates for the development of PGRs. This review aims to provide a theoretical basis for the development of economical, safe and effective PGRs utilizing allelochemicals, and emphasizes the need for further research in this area.


Assuntos
Feromônios , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Feromônios/metabolismo , Feromônios/farmacologia , Desenvolvimento Vegetal , Plantas/metabolismo , Fotossíntese
8.
Cancer Immunol Immunother ; 73(5): 91, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554157

RESUMO

BACKGROUND: Accumulation studies found that tumor-associated macrophages (TAMs) are a predominant cell in tumor microenvironment (TME), which function essentially during tumor progression. By releasing bioactive molecules, including circRNA, small extracellular vesicles (sEV) modulate immune cell functions in the TME, thereby affecting non-small cell lung cancer (NSCLC) progression. Nevertheless, biology functions and molecular mechanisms of M2 macrophage-derived sEV circRNAs in NSCLC are unclear. METHODS: Cellular experiments were conducted to verify the M2 macrophage-derived sEV (M2-EV) roles in NSCLC. Differential circRNA expression in M0 and M2-EV was validated by RNA sequencing. circFTO expression in NSCLC patients and cells was investigated via real-time PCR and FISH. The biological mechanism of circFTO in NSCLC was validated by experiments. Our team isolated sEV from M2 macrophages (M2Ms) and found that M2-EV treatment promoted NSCLC CP, migration, and glycolysis. RESULTS: High-throughput sequencing found that circFTO was highly enriched in M2-EV. FISH and RT-qPCR confirmed that circFTO expression incremented in NSCLC tissues and cell lines. Clinical studies confirmed that high circFTO expression correlated negatively with NSCLC patient survival. Luciferase reporter analysis confirmed that miR-148a-3p and PDK4 were downstream targets of circFTO. circFTO knockdown inhibited NSCLC cell growth and metastasis in in vivo experiments. Downregulating miR-148a-3p or overexpressing PDK4 restored the malignancy of NSCLC, including proliferation, migration, and aerobic glycolysis after circFTO silencing. CONCLUSION: The study found that circFTO from M2-EV promoted NSCLC cell progression and glycolysis through miR-148a-3p/PDK4 axis. circFTO is a promising prognostic and diagnostic NSCLC biomarker and has the potential to be a candidate NSCLC therapy target.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Microambiente Tumoral
9.
J Org Chem ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940722

RESUMO

Herein, a photocatalytic umpolung strategy for reductive carboxylation of imines for the synthesis of α-amino acids was disclosed. Carbon dioxide radical anion (CO2•-) generated from formate is the key single electron reductant in the reactions. An unprecedentedly broad substrate scope of imines with excellent reaction yields was obtained with carbon dioxide (CO2) and formate salt as carbon sources.

10.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 113-117, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678616

RESUMO

Burn as physical injury ranks as the fourth most prevalent trauma across the world. In this study, we aimed to compare the impact of gasoline burn and chromic acid burn on the internal organs and immune functions in rats. The results showed that the levels of methemoglobin (MHb) to total hemoglobin (Hb) as well as the Cr6+ content showed significant elevation in the chromic acid burn group relative to the gasoline burn group. HE staining was used to evaluate the histological changes in the injured tissues as well as the tissues excised from internal organs. We found that chromic acid burn-induced more severe damage to rat tissues. Gasoline burn showed no significant impact on the intestinal tissues of rats, while the chromic acid burn-induced increased cell death in rat intestines. Moreover, the results of HE staining also revealed that gasoline burn and chromic acid burn showed no evident impact on rat hearts. Gasoline burn also showed no significant effects on the liver, lungs and kidneys of rats, while the chromic acid burn caused injuries to such internal organs in comparison with the control and gasoline burn groups. In addition, the MPO activity was higher in the liver, intestine, lungs and kidneys of rats with chromic acid burn. Furthermore, the expression of inflammation response cytokines was examined in the serum of rats. The results demonstrated that the levels of IL-6, IL-1ß and TNF-α showed a significant increase in both the gasoline burn and chromic acid burn groups of rats relative to the control, and the levels were higher in the chromic acid burn group in comparison with the gasoline burn group. In conclusion, the chromic acid burn-induced more severe organ injury, inflammation and immune response compared with the gasoline burn, which may provide reference data for the clinical treatment of patients with different burn injuries.


Assuntos
Gasolina , Animais , Masculino , Ratos , Fígado/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/imunologia , Ratos Sprague-Dawley , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Queimaduras Químicas/patologia , Queimaduras Químicas/metabolismo , Queimaduras Químicas/imunologia , Peroxidase/metabolismo , Inflamação/patologia
11.
Biochem Genet ; 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367128

RESUMO

The global prevalence of iron deficiency-induced "hidden hunger" highlights a critical health concern, underscoring the pressing need to improve iron nutrition through safe and efficient means, such as increasing iron intake from plant-based foods. Yellow Stripe-Like (YSL) genes play a crucial role in long-distance iron transport between source and sink tissues in plants. Here, we report on the analysis of YSL family genes in the common bean (Phaseolus vulgaris L.), an iron-rich legume crop. We identified 9 YSL genes in the common bean genome using BLAST and HMM methods. Gene duplication analysis revealed that PvYSL7a and PvYSL7b originated through tandem duplication events. Structural analysis noted an absence of conservative motifs in PvYSL3b and PvYSL7a, which led to distinct predicted 3D protein structures. Leveraging publicly available RNA-seq data from developing bean pods, the expression patterns of PvYSL genes alongside pod and seed development were analyzed. Notably, PvYSL7a and PvYSL7b, as well as PvYSL1a and PvYSL1b, exhibited diverged expression patterns in seeds, signifying their functional divergence in this tissue. Moreover, PvYSL3a and PvYSL3b exhibited divergent expression patterns in both pod walls and seeds during pod development, underscoring their distinct roles in facilitating iron transportation between pods and seeds. This study provides valuable insights into the gene regulatory basis of iron accumulation in bean pods and seeds.

12.
Int J Phytoremediation ; 26(7): 1117-1132, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38099523

RESUMO

Little information is available on the influence of the compound use of intercropping (IN) and arbuscular mycorrhizal fungus (AMF) on Cd accumulation and the expression of Cd transporter genes in two intercropped plants. A pot experiment was conducted to study the influences of IN and AMF-Glomus versiforme on growth and Cd uptake of two intercropped plants-maize and Cd hyperaccumulator Sphagneticola calendulacea, and the expression of Cd transporter genes in maize in Cd-polluted soils. IN, AMF and combined treatments of IN and AMF (IN + AMF) obviously improved biomass, photosynthesis and total antioxidant capacities of two plants. Moreover, single and compound treatments of IN and AMF evidently reduced Cd contents in maize, and the greatest decreases appeared in the compound treatment. However, Cd contents of S. calendulacea in IN, AMF and IN + AMF groups were notably improved. Furthermore, the single and compound treatments of IN and AMF significantly downregulated the expression levels of Nramp1, HMA1, ABCC1 and ABCC10 in roots and leaves, and the largest decreases were observed in the combined treatment. Our work first revealed that the combined use of IN and AMF appeared to have a synergistic effect on decreasing Cd content by downregulating the expression of Cd transporter genes in maize.


Assuntos
Biodegradação Ambiental , Cádmio , Micorrizas , Poluentes do Solo , Zea mays , Zea mays/metabolismo , Zea mays/microbiologia , Micorrizas/fisiologia , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Glomeromycota/fisiologia , Asteraceae/metabolismo
13.
J Sci Food Agric ; 104(10): 6008-6017, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38437455

RESUMO

BACKGROUND: The alteration of chromatin accessibility plays an important role in plant responses to abiotic stress. Carbon-based nanomaterials (CBNMs) have attracted increasing interest in agriculture due to their potential impact on crop productivity, showcasing effects on plant biological processes at transcriptional levels; however, their impact on chromatin accessibility remains unknown. RESULTS: This study found that fullerenol can penetrate the seed coat of pea to mitigate the reduction of seed germination caused by osmotic stress. RNA sequencing (RNA-seq) revealed that the application of fullerenol caused the high expression of genes related to oxidoreduction to return to a normal level. Assay for transposase accessible chromatin sequencing (ATAC-seq) confirmed that fullerenol application reduced the overall levels of chromatin accessibility of numerous genes, including those related to environmental signaling, transcriptional regulation, and metabolism. CONCLUSION: This study suggests that fullerenol alleviates osmotic stress on various fronts, encompassing antioxidant, transcriptional, and epigenetic levels. This advances knowledge of the working mechanism of this nanomaterial within plant cells. © 2024 Society of Chemical Industry.


Assuntos
Montagem e Desmontagem da Cromatina , Fulerenos , Germinação , Osmose , Pisum sativum , Sementes , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Germinação/efeitos dos fármacos , Fulerenos/farmacologia , Pisum sativum/metabolismo , Pisum sativum/genética , Pisum sativum/química , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Pressão Osmótica
14.
Thorax ; 78(1): 76-84, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35304425

RESUMO

BACKGROUND: There is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups. METHODS: This sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features. RESULTS: Of 1860 eligible Chinese subjects who underwent polysomnography (2006-2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea-hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation <90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate-severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95). CONCLUSIONS: OSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Estudos de Coortes , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/tratamento farmacológico , Sono , Polissonografia
15.
J Virol ; 96(8): e0027922, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35353002

RESUMO

Sp100 (speckled protein 100 kDa) is a constituent component of nuclear structure PML (promyelocytic leukemia) bodies, playing important roles in mediating intrinsic and innate immunity. The Sp100 gene encodes four isoforms with distinct roles in the transcriptional regulation of both cellular and viral genes. Since Sp100 is a primary intranuclear target of infected-cell protein 0 (ICP0), an immediate early E3 ligase encoded by herpes simplex virus 1 (HSV-1), previous investigations attempting to analyze the functions of individual Sp100 variants during HSV-1 infection mostly avoided using a wild-type virus. Therefore, the role of Sp100 under natural infection by HSV-1 remains to be clarified. Here, we reappraised the antiviral capacity of four Sp100 isoforms during infection by a nonmutated HSV-1, examined the molecular behavior of the Sp100 protein in detail, and revealed the following intriguing observations. First, Sp100 isoform A (Sp100A) inhibited wild-type HSV-1 propagation in HEp-2, Sp100-/-, and PML-/- cells. Second, endogenous Sp100 is located in both the nucleus and the cytoplasm. During HSV-1 infection, the nuclear Sp100 level decreased drastically upon the detection of ICP0 in the same subcellular compartment, but cytosolic Sp100 remained stable. Third, transfected Sp100A showed subcellular localizations similar to those of endogenous Sp100 and matched the protein size of endogenous cytosolic Sp100. Fourth, HSV-1 infection induced increased secretion of endogenous Sp100 and ectopically expressed Sp100A, which copurified with extracellular vesicles (EVs) but not infectious virions. Fifth, the Sp100A level in secreting cells positively correlated with its level in EVs, and EV-associated Sp100A restricted HSV-1 in recipient cells. IMPORTANCE Previous studies show that the PML body component Sp100 protein is immediately targeted by ICP0 of HSV-1 in the nucleus during productive infection. Therefore, extensive studies investigating the interplay of Sp100 isoforms with HSV-1 were conducted using a mutant virus lacking ICP0 or in the absence of infection. The role of Sp100 variants during natural HSV-1 infection remains blurry. Here, we report that Sp100A potently and independently inhibited wild-type HSV-1 and that during HSV-1 infection, cytosolic Sp100 remained stable and was increasingly secreted into the extracellular space, in association with EVs. Furthermore, the Sp100A level in secreting cells positively correlated with its level in EVs and the anti-HSV-1 potency of these EVs in recipient cells. In summary, this study implies an active antiviral role of Sp100A during wild-type HSV-1 infection and reveals a novel mechanism of Sp100A to restrict HSV-1 through extracellular communications.


Assuntos
Antígenos Nucleares , Autoantígenos , Herpes Simples , Herpesvirus Humano 1 , Interações entre Hospedeiro e Microrganismos , Corpos Nucleares da Leucemia Promielocítica , Antígenos Nucleares/metabolismo , Antivirais/metabolismo , Autoantígenos/metabolismo , Herpes Simples/genética , Herpesvirus Humano 1/metabolismo , Humanos , Corpos Nucleares da Leucemia Promielocítica/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
16.
Nucleic Acids Res ; 49(D1): D1268-D1275, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33270889

RESUMO

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Bases de Dados Genéticas , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Biomarcadores Tumorais/metabolismo , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Variações do Número de Cópias de DNA , Progressão da Doença , Elementos Facilitadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , Análise em Microsséries , Anotação de Sequência Molecular , Mutação , Neoplasias/classificação , Neoplasias/diagnóstico , Neoplasias/metabolismo , Software , Transcriptoma
17.
Pestic Biochem Physiol ; 193: 105431, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37248009

RESUMO

The entomopathogenic fungus is recognized as an ideal alternative to chemical pesticides, nonetheless, its efficacy is often limited by insect's innate immune system. The suppression of the host immunity may overcome the obstacle and promote the toxicity of the fungi. Here, by using an entomopathogenic fungus Beauveria bassiana and immune genes dsRNA-expressing bacteria, we explored the potentially synergistic toxicity of the two agents on a leaf beetle Plagiodera versicolora (Coleoptera: Chrysomelidae). We first determined the susceptibilities of P. versicolora to a B. bassiana 476 strain (hereafter referred to Bb476). And the immune genes were identified based on the transcriptome of Bb476 challenged beetles. Subsequently, five immune genes (PGRP1, Toll1, Domeless,SPN1,and Lysozyme) were targeted by feeding dsRNA-expressing bacteria, which produced a 71.4, 39.0, 72.0, 49.0, and 68.7% gene silencing effect, respectively. Furthermore, we found a significantly increased mortality of P. versicolora when combined the Bb476 and the immune suppressive dsRNAs. Taking together, this study highlights the importance of insect immunity in the defense of entomopathogens and also paves the way toward the development of a more efficient pest management strategy that integrates both entomopathogens and immune suppressive dsRNAs.


Assuntos
Beauveria , Besouros , Controle Biológico de Vetores , Animais , Bactérias , Beauveria/genética , Besouros/microbiologia , Inseticidas
18.
Mikrochim Acta ; 190(5): 185, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37071210

RESUMO

The SERS intensity of analytes is primarily influenced by the density and distribution of hotspots, which are often difficult to manipulate or regulate. In this study, cucurbit[8]uril (CB[8]), a kind of rigid macrocyclic molecule, was introduced to achieve ~ 1-nm nanogap between gold nanoparticles to increase the density of SERS hotspots. Three kinds of estrogens (estrone (E1), bisphenol A (BPA), and hexestrol (DES)) which are molecules with weak SERS signals were targeted in the hotspots by CB[8] to further improve the sensitivity and selectivity of SERS. It was demonstrated that CB[8] can link gold nanoparticles together through carbonyl groups. In addition, the host-guest interaction of CB[8] and estrogens was proved from the nuclear magnetic resonance hydrogen and infrared spectra. In the presence of CB[8], the SERS intensities of E1, BPA, and DES were increased to 19-fold, 74-fold, and 4-fold, respectively, and the LOD is 3.75 µM, 1.19 µM, and 8.26 µM, respectively. Furthermore, the proposed SERS method was applied to actual milk sample analysis with recoveries of E1 (85.0 ~ 112.8%), BPA (83.0 ~ 103.7%), and DES (62.6 ~ 132.0%). It is expected that the proposed signal enlarging strategy can be applied to  other analytes after further development.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Estrogênios , Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Nanoestruturas/química
19.
J Environ Manage ; 331: 117189, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634420

RESUMO

This study developed a comprehensive techno-economic assessment (TEA) framework to evaluate an innovative algae resource recovery and near zero-liquid discharge potable reuse system (i.e., the main system) in comparison with a conventional potable water reuse system (i.e., the benchmark system). The TEA study aims to estimate the levelized costs of water of individual units and integrated processes including secondary wastewater treatment, advanced water purification for potable reuse, and sludge treatment. This would provide decision-makers valuable information regarding the capital and operational costs of the innovative main system versus a typical potable water reuse treatment train, along with possible routes of cost optimization and improvements for the design of full-scale facilities. The main system consists of (i) a novel algal-based wastewater treatment coupled with a dual forward osmosis and seawater reverse osmosis (Algal FO-SWRO) membranes system for potable water reuse and hydrothermal liquefaction (HTL) to produce bioenergy and subsequent nutrients extraction from the harvested algal biomass. The benchmark system includes (ii) an advanced water purification facility (AWPF) that consists of a conventional activated sludge biological treatment (CAS), microfiltration (MF), brackish water reverse osmosis (BWRO), ultraviolet/advanced oxidation process (UV-AOP), and granular activated carbon (GAC), with anaerobic digestion for sludge treatment. Capital expenditures (CAPEX) and operational expenditures (OPEX) were calculated for each unit of both systems (i.e., sub-systems). Based on a 76% overall water recovery designed for the benchmark system, the water cost was estimated at $2.03/m3. The highest costs in the benchmark system were found on the CAS and the anaerobic digester, with the UV-AOP combined with GAC for hydrogen peroxide (H2O2) quenching as the driving factor in the increased costs of the system. The cost of the main system, based on an overall 88% water recovery, was estimated to be $1.97/m3, with costs mostly driven by the FO and SWRO membranes. With further cost reduction and optimization for FO membranes such as membrane cost, water recovery, and flux, the main system can provide a much more economically viable alternative in its application than a typical benchmark system.


Assuntos
Água Potável , Purificação da Água , Águas Residuárias , Esgotos , Peróxido de Hidrogênio , Carvão Vegetal , Osmose , Membranas Artificiais
20.
J Environ Manage ; 331: 117293, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36657205

RESUMO

This study applied a life cycle assessment (LCA) methodology for a comparative environmental analysis between an innovative algae resource recovery and near zero-liquid discharge potable reuse system (i.e., the main system) versus a conventional potable reuse system (i.e., the benchmark system) through energy use and greenhouse gas (GHG) emissions. The objective of this study is to demonstrate that pilot-scale data coupled with LCA would provide valuable information for system optimization, integration, and improvements for the design of environmentally sustainable full-scale systems. This study also provides decision-makers valuable information regarding the energy demand and environmental impact of this innovative main system compared to a typical tried-and-true system for potable water reuse. The main system consists of a novel algal-based wastewater treatment coupled with a dual forward osmosis and seawater reverse osmosis (Algal FO-SWRO) membranes system for potable water recovery and hydrothermal liquefaction (HTL) to recover biofuels and valuable nutrients from the harvested algal biomass. The benchmark system refers to the current industry standard technologies for potable water reuse and waste management including a secondary biological treatment, microfiltration (MF), brackish water reverse osmosis (BWRO), ultraviolet/advanced oxidation process (UV-AOP), and granular activated carbon (GAC), as well as anaerobic digestion for sludge treatment. Respective energy and GHG emissions of both systems were normalized and compared considering 1 m3 of water recovered. Based on an overall water recovery of 76% designed for the benchmark system, the energy consumption totaled 4.83 kWh/m3, and the system was estimated to generate 2.42 kg of CO2 equivalent/m3 with most of the emissions coming from the biological treatment. The main system, based on an overall water recovery of 88%, was estimated to consume 4.76 kWh/m3 and emit 1.49 kg of CO2 eq/m3. The main system has high environmental resilience and can recover bioenergy and nutrients from wastewater with zero waste disposal. With the application of energy recovery devices for the HTL and the SWRO, increase in water recovery of the FO membrane, and replacement of the SWRO membrane with BWRO, the main system provides an energy-competitive and environmentally positive alternative with an energy demand of 2.57 kWh/m3 and low GHG emissions of 0.94 kg CO2 eq/m3.


Assuntos
Água Potável , Gases de Efeito Estufa , Purificação da Água , Animais , Dióxido de Carbono , Purificação da Água/métodos , Águas Residuárias , Água do Mar , Osmose , Estágios do Ciclo de Vida
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