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1.
Nature ; 626(7999): 617-625, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081298

RESUMO

The outer membrane in Gram-negative bacteria consists of an asymmetric phospholipid-lipopolysaccharide bilayer that is densely packed with outer-membrane ß-barrel proteins (OMPs) and lipoproteins1. The architecture and composition of this bilayer is closely monitored and is essential to cell integrity and survival2-4. Here we find that SlyB, a lipoprotein in the PhoPQ stress regulon, forms stable stress-induced complexes with the outer-membrane proteome. SlyB comprises a 10 kDa periplasmic ß-sandwich domain and a glycine zipper domain that forms a transmembrane α-helical hairpin with discrete phospholipid- and lipopolysaccharide-binding sites. After loss in lipid asymmetry, SlyB oligomerizes into ring-shaped transmembrane complexes that encapsulate ß-barrel proteins into lipid nanodomains of variable size. We find that the formation of SlyB nanodomains is essential during lipopolysaccharide destabilization by antimicrobial peptides or acute cation shortage, conditions that result in a loss of OMPs and compromised outer-membrane barrier function in the absence of a functional SlyB. Our data reveal that SlyB is a compartmentalizing transmembrane guard protein that is involved in cell-envelope proteostasis and integrity, and suggest that SlyB represents a larger family of broadly conserved lipoproteins with 2TM glycine zipper domains with the ability to form lipid nanodomains.


Assuntos
Proteínas da Membrana Bacteriana Externa , Membrana Celular , Bactérias Gram-Negativas , Bicamadas Lipídicas , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Glicina/metabolismo , Lipopolissacarídeos/metabolismo , Lipoproteínas/química , Lipoproteínas/metabolismo , Fosfolipídeos/metabolismo , Sítios de Ligação , Proteostase , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Proteoma/química , Proteoma/metabolismo , Regulon , Domínios Proteicos , Peptídeos Antimicrobianos/metabolismo , Bactérias Gram-Negativas/química , Bactérias Gram-Negativas/citologia , Bactérias Gram-Negativas/metabolismo
2.
Plant Cell ; 35(5): 1548-1571, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36718530

RESUMO

Inter-organelle communication is an integral subcellular process in cellular homeostasis. In plants, cellular membrane lipids are synthesized in the plastids and endoplasmic reticulum (ER). However, the crosstalk between these organelles in lipid biosynthesis remains largely unknown. Here, we show that a pair of lipid phosphate phosphatases (LPPs) with differential subcellular localizations is required for ER glycerolipid metabolism in Arabidopsis (Arabidopsis thaliana). LPPα2 and LPPε1, which function as phosphatidic acid phosphatases and thus catalyze the core reaction in glycerolipid metabolism, were differentially localized at ER and chloroplast outer envelopes despite their similar tissue expression pattern. No mutant phenotype was observed in single knockout mutants; however, genetic suppression of these LPPs affected pollen growth and ER phospholipid biosynthesis in mature siliques and seeds with compromised triacylglycerol biosynthesis. Although chloroplast-localized, LPPε1 was localized close to the ER and ER-localized LPPα2. This proximal localization is functionally relevant, because overexpression of chloroplastic LPPε1 enhanced ER phospholipid and triacylglycerol biosynthesis similar to the effect of LPPα2 overexpression in mature siliques and seeds. Thus, ER glycerolipid metabolism requires a chloroplast-localized enzyme in Arabidopsis, representing the importance of inter-organelle communication in membrane lipid homeostasis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fosfatidato Fosfatase/genética , Fosfatidato Fosfatase/metabolismo , Retículo Endoplasmático/metabolismo , Fosfolipídeos/metabolismo , Lipídeos de Membrana/metabolismo , Metabolismo dos Lipídeos/genética , Triglicerídeos/metabolismo
3.
Chem Soc Rev ; 53(10): 5190-5226, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38586901

RESUMO

Etching technology - one of the representative modern semiconductor device makers - serves as a broad descriptor for the process of removing material from the surfaces of various materials, whether partially or entirely. Meanwhile, thinning technology represents a novel and highly specialized approach within the realm of etching technology. It indicates the importance of achieving an exceptionally sophisticated and precise removal of material, layer-by-layer, at the nanoscale. Notably, thinning technology has gained substantial momentum, particularly in top-down strategies aimed at pushing the frontiers of nano-worlds. This rapid development in thinning technology has generated substantial interest among researchers from diverse backgrounds, including those in the fields of chemistry, physics, and engineering. Precisely and expertly controlling the layer numbers of 2D materials through the thinning procedure has been considered as a crucial step. This is because the thinning processes lead to variations in the electrical and optical characteristics. In this comprehensive review, the strategies for top-down thinning of representative 2D materials (e.g., graphene, black phosphorus, MoS2, h-BN, WS2, MoSe2, and WSe2) based on conventional plasma-assisted thinning, integrated cyclic plasma-assisted thinning, laser-assisted thinning, metal-assisted splitting, and layer-resolved splitting are covered in detail, along with their mechanisms and benefits. Additionally, this review further explores the latest advancements in terms of the potential advantages of semiconductor devices achieved by top-down 2D material thinning procedures.

4.
Emerg Infect Dis ; 30(5): 991-994, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38666642

RESUMO

African swine fever virus (ASFV) genotype II is endemic to Vietnam. We detected recombinant ASFV genotypes I and II (rASFV I/II) strains in domestic pigs from 6 northern provinces in Vietnam. The introduction of rASFV I/II strains could complicate ongoing ASFV control measures in the region.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Genótipo , Filogenia , Animais , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/classificação , Vietnã/epidemiologia , Febre Suína Africana/epidemiologia , Febre Suína Africana/virologia , Suínos , Sus scrofa/virologia , Recombinação Genética
6.
Plant Cell Physiol ; 65(2): 199-215, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37951591

RESUMO

Previous studies on the intricate interactions between plants and microorganisms have revealed that fungal volatile compounds (VCs) can affect plant growth and development. However, the precise mechanisms underlying these actions remain to be delineated. In this study, we discovered that VCs from the soilborne fungus Tolypocladium inflatum GT22 enhance the growth of Arabidopsis. Remarkably, priming Arabidopsis with GT22 VCs caused the plant to display an enhanced immune response and mitigated the detrimental effects of both pathogenic infections and copper stress. Transcriptomic analyses of Arabidopsis seedlings treated with GT22 VCs for 3, 24 and 48 h revealed that 90, 83 and 137 genes were differentially expressed, respectively. The responsive genes are known to be involved in growth, hormone regulation, defense mechanisms and signaling pathways. Furthermore, we observed the induction of genes related to innate immunity, hypoxia, salicylic acid biosynthesis and camalexin biosynthesis by GT22 VCs. Among the VCs emitted by GT22, exposure of Arabidopsis seedlings to limonene promoted plant growth and attenuated copper stress. Thus, limonene appears to be a key mediator of the interaction between GT22 and plants. Overall, our findings provide evidence that fungal VCs can promote plant growth and enhance both biotic and abiotic tolerance. As such, our study suggests that exposure of seedlings to T. inflatum GT22 VCs may be a means of improving crop productivity. This study describes a beneficial interaction between T. inflatun GT22 and Arabidopsis. Our investigation of microorganism function in terms of VC activities allowed us to overcome the limitations of traditional microbial application methods. The importance of this study lies in the discovery of T. inflatun GT22 as a beneficial microorganism. This soilborne fungus emits VCs with plant growth-promoting effects and the ability to alleviate both copper and pathogenic stress. Furthermore, our study offers a valuable approach to tracking the activities of fungal VC components via transcriptomic analysis and sheds light on the mechanisms through which VCs promote plant growth and induce resistance. This research significantly advances our knowledge of VC applications and provides an example for further investigations within this field.


Assuntos
Arabidopsis , Hypocreales , Arabidopsis/genética , Cobre/farmacologia , Cobre/metabolismo , Limoneno/metabolismo , Limoneno/farmacologia , Hypocreales/metabolismo , Plantas/metabolismo , Plântula/metabolismo , Regulação da Expressão Gênica de Plantas
7.
Lancet ; 401(10373): 281-293, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36566761

RESUMO

BACKGROUND: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. METHODS: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older-or aged 18 years or older with relevant comorbidities-and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81-1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. INTERPRETATION: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. FUNDING: UK National Institute for Health and Care Research.


Assuntos
COVID-19 , Adulto , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinas contra COVID-19 , Teorema de Bayes , Estudos Prospectivos , Resultado do Tratamento
8.
Microbiology (Reading) ; 170(3)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38568202

RESUMO

Understanding the evolution of antibiotic resistance is important for combating drug-resistant bacteria. In this work, we investigated the adaptive response of Pseudomonas aeruginosa to ciprofloxacin. Ciprofloxacin-susceptible P. aeruginosa ATCC 9027, CIP-E1 (P. aeruginosa ATCC 9027 exposed to ciprofloxacin for 14 days) and CIP-E2 (CIP-E1 cultured in antibiotic-free broth for 10 days) were compared. Phenotypic responses including cell morphology, antibiotic susceptibility, and production of pyoverdine, pyocyanin and rhamnolipid were assessed. Proteomic responses were evaluated using comparative iTRAQ labelling LC-MS/MS to identify differentially expressed proteins (DEPs). Expression of associated genes coding for notable DEPs and their related regulatory genes were checked using quantitative reverse transcriptase PCR. CIP-E1 displayed a heterogeneous morphology, featuring both filamentous cells and cells with reduced length and width. By contrast, although filaments were not present, CIP-E2 still exhibited size reduction. Considering the MIC values, ciprofloxacin-exposed strains developed resistance to fluoroquinolone antibiotics but maintained susceptibility to other antibiotic classes, except for carbapenems. Pyoverdine and pyocyanin production showed insignificant decreases, whereas there was a significant decrease in rhamnolipid production. A total of 1039 proteins were identified, of which approximately 25 % were DEPs. In general, there were more downregulated proteins than upregulated proteins. Noted changes included decreased OprD and PilP, and increased MexEF-OprN, MvaT and Vfr, as well as proteins of ribosome machinery and metabolism clusters. Gene expression analysis confirmed the proteomic data and indicated the downregulation of rpoB and rpoS. In summary, the response to CIP involved approximately a quarter of the proteome, primarily associated with ribosome machinery and metabolic processes. Potential targets for bacterial interference encompassed outer membrane proteins and global regulators, such as MvaT.


Assuntos
Ciprofloxacina , Infecções por Pseudomonas , Humanos , Ciprofloxacina/farmacologia , Pseudomonas aeruginosa/genética , Cromatografia Líquida , Proteômica , Piocianina , Espectrometria de Massas em Tandem , Antibacterianos/farmacologia
9.
BMC Plant Biol ; 24(1): 440, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778295

RESUMO

BACKGROUND: Exploring the relationship between parasitic plants and answering taxonomic questions is still challenging. The subtribe Scurrulinae (Loranthaceae), which has a wide distribution in Asia and Africa, provides an excellent example to illuminate this scenario. Using a comprehensive taxon sampling of the subtribe, this study focuses on infer the phylogenetic relationships within Scurrulinae, investigate the phylogeny and biogeography of the subtribe, and establish a phylogenetically-based classification incorporating both molecular and morphological evidence. We conducted phylogenetic, historical biogeography, and ancestral character state reconstruction analyses of Scurrulinae based on the sequences of six DNA regions from 89 individuals to represent all five tribes of the Loranthaceae and the dataset from eleven morphological characters. RESULTS: The results strongly support the non-monophyletic of Scurrulinae, with Phyllodesmis recognized as a separate genus from its allies Taxillus and Scurrula based on the results from molecular data and morphological character reconstruction. The mistletoe Scurrulinae originated in Asia during the Oligocene. Scurrulinae was inferred to have been widespread in Asia but did not disperse to other areas. The African species of Taxillus, T. wiensii, was confirmed to have originated in Africa from African Loranthaceae ca. 17 Ma, and evolved independently from Asian members of Taxillus. CONCLUSIONS: This study based on comprehensive taxon sampling of the subtribe Scurrulinae, strongly supports the relationship between genera. The taxonomic treatment for Phyllodesmis was provided. The historical biogeography of mistletoe Scurrulinae was determined with origin in Asia during the Oligocene. Taxillus and Scurrula diverged during the climatic optimum in the middle Miocene. Taxillus wiensii originated in Africa from African Loranthaceae, and is an independent lineage from the Asian species of Taxillus. Diversification of Scurrulinae and the development of endemic species in Asia may have been supported by the fast-changing climate, including cooling, drying, and the progressive uplift of the high mountains in central Asia, especially during the late Pliocene and Pleistocene.


Assuntos
Loranthaceae , Filogenia , Filogeografia , Loranthaceae/genética , África , Ásia , Evolução Biológica , DNA de Plantas/genética , Evolução Molecular , Análise de Sequência de DNA
10.
J Transl Med ; 22(1): 618, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961476

RESUMO

BACKGROUND: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. METHODS: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. RESULTS: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. CONCLUSIONS: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.


Assuntos
Metilação de DNA , Genoma Humano , Neoplasias , Redes Neurais de Computação , Humanos , Metilação de DNA/genética , Neoplasias/genética , Neoplasias/sangue , Neoplasias/diagnóstico , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Especificidade de Órgãos/genética , Algoritmos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38479823

RESUMO

OBJECTIVE: The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare. METHODS: Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series (SCCS) analysis investigated the association between pneumococcal vaccination and IMID flare. The SCCS observation period was up-to six-month before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90-days post-vaccination exposed, and the remaining unexposed periods. RESULTS: We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3,804 with axial spondyloarthritis and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years (32%), with IBD (42%), and without additional indication(s) for vaccination (46%). In the vaccine-safety study, data for 1,067, 935, and 451vaccinated patients with primary-care consultations for joint pain, AIRD flare and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, AIRD flare and IBD flare in the exposed period with incidence rate ratios (95% Confidence Interval) 0.95 (0.83-1.09), 1.05 (0.92-1.19), and 0.83 (0.65-1.06) respectively. CONCLUSION: Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare.

12.
Cytotherapy ; 26(3): 242-251, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38142382

RESUMO

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.


Assuntos
Neoplasias de Cabeça e Pescoço , Células Matadoras Naturais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Modelos Animais de Doenças , Linhagem Celular Tumoral , Camundongos Endogâmicos NOD , Camundongos SCID , Células Matadoras Naturais/metabolismo , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/metabolismo
13.
BMC Cancer ; 24(1): 410, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566115

RESUMO

BACKGROUND: High expression of the glycosyltransferase UGT2B17 represents an independent adverse prognostic marker in chronic lymphocytic leukemia (CLL). It also constitutes a predictive marker for therapeutic response and a drug resistance mechanism. The key determinants driving expression of the UGT2B17 gene in normal and leukemic B-cells remain undefined. The UGT2B17 transcriptome is complex and is comprised of at least 10 alternative transcripts, identified by previous RNA-sequencing of liver and intestine. We hypothesized that the transcriptional program regulating UGT2B17 in B-lymphocytes is distinct from the canonical expression previously characterized in the liver. RESULTS: RNA-sequencing and genomics data revealed a specific genomic landscape at the UGT2B17 locus in normal and leukemic B-cells. RNA-sequencing and quantitative PCR data indicated that the UGT2B17 enzyme is solely encoded by alternative transcripts expressed in CLL patient cells and not by the canonical transcript widely expressed in the liver and intestine. Chromatin accessible regions (ATAC-Seq) in CLL cells mapped with alternative promoters and non-coding exons, which may be derived from endogenous retrotransposon elements. By luciferase reporter assays, we identified key cis-regulatory STAT3, RELA and interferon regulatory factor (IRF) binding sequences driving the expression of UGT2B17 in lymphoblastoid and leukemic B-cells. Electrophoretic mobility shift assays and pharmacological inhibition demonstrated key roles for the CLL prosurvival transcription factors STAT3 and NF-κB in the leukemic expression of UGT2B17. CONCLUSIONS: UGT2B17 expression in B-CLL is driven by key regulators of CLL progression. Our data suggest that a NF-κB/STAT3/IRF/UGT2B17 axis may represent a novel B-cell pathway promoting disease progression and drug resistance.


Assuntos
Leucemia Linfocítica Crônica de Células B , NF-kappa B , Humanos , NF-kappa B/metabolismo , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Prognóstico , Apoptose , RNA , Glucuronosiltransferase/genética , Antígenos de Histocompatibilidade Menor
14.
Liver Int ; 44(2): 316-329, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010880

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a growing public health threat and becoming the leading cause of liver transplantation. Nevertheless, no approved specific treatment is currently available for NAFLD. The pathogenesis of NAFLD is multifaceted and not yet fully understood. Accumulating evidence suggests a significant role of the complement system in the development and progression of NAFLD. Here, we provide an overview of the complement system, incorporating the novel concept of complosome, and summarise the up-to-date evidence elucidating the association between complement dysregulation and the pathogenesis of NAFLD. In this process, the extracellular complement system is activated through various pathways, thereby directly contributing to, or working together with other immune cells in the disease development and progression. We also introduce the complosome and assess the evidence that implicates its potential influence in NAFLD through its direct impact on hepatocytes or non-parenchymal liver cells. Additionally, we expound upon how complement system and the complosome may exert their effects in relation with hepatic zonation in NAFLD. Furthermore, we discuss the potential therapeutic implications of targeting the complement system, extracellularly and intracellularly, for NAFLD treatment. Finally, we present future perspectives towards a better understanding of the complement system's contribution to NAFLD.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/patologia , Hepatócitos/metabolismo
15.
AIDS Behav ; 28(6): 1858-1881, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38478323

RESUMO

Tobacco smoking is highly prevalent among people living with HIV (PLWH), yet there is a lack of data on smoking behaviours and effective treatments in this population. Understanding factors influencing tobacco smoking and cessation is crucial to guide the design of effective interventions. This systematic review and meta-analysis of studies conducted in both high-income (HICs) and low- and middle-income countries (LMICs) synthesised existing evidence on associated factors of smoking and cessation behaviour among PLWH. Male gender, substance use, and loneliness were positively associated with current smoking and negatively associated with smoking abstinence. The association of depression with current smoking and lower abstinence rates were observed only in HICs. The review did not identify randomised controlled trials conducted in LMICs. Findings indicate the need to integrate smoking cessation interventions with mental health and substance use services, provide greater social support, and address other comorbid conditions as part of a comprehensive approach to treating tobacco use in this population. Consistent support from health providers trained to provide advice and treatment options is also an important component of treatment for PLWH engaged in care, especially in LMICs.


Assuntos
Infecções por HIV , Abandono do Hábito de Fumar , Fumar Tabaco , Humanos , Infecções por HIV/psicologia , Infecções por HIV/complicações , Abandono do Hábito de Fumar/psicologia , Fumar Tabaco/epidemiologia , Masculino , Feminino , Países em Desenvolvimento , Prevalência , Depressão/epidemiologia , Depressão/psicologia , Apoio Social
16.
Physiol Plant ; 176(3): e14354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769079

RESUMO

Female gametogenesis has been rarely studied due to gametophyte lethality and the unavailability of related genetic resources. In this study, we identified a rice ATP-binding cassette transporter, OsABCB24, whose null function displayed a significantly reduced seed setting rate by as much as 94%-100% compared with that of the wild type (WT). The reciprocal cross of WT and mutant plants demonstrated that the female reproductive organs in mutants were functionally impaired. Confocal microscopy observations revealed that, although megasporogenesis remained unaffected in CRISPR/Cas9 osabcb24 mutants, the formation of female gametophytes was interrupted. Additionally, the structure of the syncytial nucleus was impaired during the initial stages of endosperm formation. Histochemical analysis showed that OsABCB24 was preferentially expressed at the conjunction of receptacle and ovary, spanning from the functional megaspore stage to the two-nucleate embryo sac stage. Further, OsABCB24 was identified as an endoplasmic reticulum membrane-localized protein. Notably, the overexpression of OsABCB24 triggered a 1.5- to 2-fold increase in grain production compared to the WT. Our findings showed that OsABCB24 plays a key role in both female gametophyte development and the early development of seeds.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Regulação da Expressão Gênica de Plantas , Oryza , Óvulo Vegetal , Proteínas de Plantas , Sementes , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Óvulo Vegetal/crescimento & desenvolvimento , Óvulo Vegetal/genética , Óvulo Vegetal/metabolismo , Mutação/genética , Plantas Geneticamente Modificadas
17.
Nanotechnology ; 35(34)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38806017

RESUMO

In this study, magnetic material based on graphene oxide (GO) was developed for enhanced adsorption capacity for heavy metals. The Fe3O4nanoparticles were combined with the GO material using a chitosan (CS) binder to obtain the CS-Fe3O4/GO nanocomposite. The adsorption capacity of this nanocomposite was evaluated by removing heavy metals including Ni2+ions. When GO was composed with Fe3O4and CS, the GO films were densely covered with ferromagnetic particles, which were bound and densely distributed on the GO film surface due to the interaction between GO and CS. The optimal conditions for the complexation of Ni2+and 4-(2-pyridyl azo)-rezoxine (PAR) are 1 ml Ni2+, 2 ml PAR 100 mg l-1,pH= 6 (adjusted with 0.7 ml of the 0.1 M K2HPO4solution) and a complexation time of 20 min. After 50 min of adsorption, the Ni2+removal efficiency of the CS-Fe3O4/GO nanocomposite reached 81.21% and the corresponding adsorption capacity was 2.03 mg g-1. The Ni2+removal process followed the first-order model and Freundlich isotherm. This process was spontaneous (ΔGo< 0) and an exothermic process (ΔHo= -1128.875 J·mol-1). In addition, the factors affecting this process were investigated, including thepHsolution, the dosage of the CS-Fe3O4/GO nanocomposite and the initial Ni2+concentration. The CS-Fe3O4/GO nanocomposite showed a potential adsorption capacity in removing Ni2+at low concentrations from wastewater.

18.
Nanotechnology ; 35(28)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38412533

RESUMO

Transparent heaters (THs) find widespread application in various indoor and outdoor settings, such as LCD panels and motorcycle helmet visors. Among the materials used for efficient TH performance, the AgNW network stands out due to its high conductivity, substantial transmittance, and minimal solution requirement. Extensive research has been directed towards enhancing AgNW characteristics, focusing on smaller diameters and longer wires. In TH applications, the primary considerations include a rapid response and elevated temperature. Consequently, this research delves into investigating the impact of parameters like diameter, length, and density on random AgNW networks under varying applied voltages. The finite element method is employed for analyzing temperature changes in response to voltage application, particularly in scenarios involving small-scale setups with high-density and high-percolation AgNW networks. The results reveal a significant increase in the thermal transition rate, ranging from 28% to 36%, with varying densities in the random network. Within the same density, the AgNW network with larger diameters and lengths demonstrates the highest temperatures, aligning with previous calculations. Furthermore, a trade-off exists between optical properties in smaller diameters and electrical properties in larger diameters within a relatively narrow temperature range.

19.
Nanotechnology ; 35(38)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958589

RESUMO

Green energy technology is generally becoming one of hot issues that need to be solved due to the adverse effects on the environment of fossil fuels. One of the strategies being studied and developed by theorists and experimentalists is the use of photoelectrochemical (PEC) cells, which are emerging as a candidate to produce hydrogen from water splitting. However, creating photoelectrodes that meet the requirements for PEC water splitting has emerged as the primary obstacle in bringing this technology to commercial fruition. Here, we construct a heterostructure, which consists of MoS2/TiO2/Au nanoparticles (NPs) to overcome the drawbacks of the photoanode. Owing to the dependence on charge transfer, the bandgap of MoS2/TiO2and the utilization the Au NPs as a stimulant for charges separation of TiO2by localized surface plasmon resonances effect as well as the increase of hot electron injection to cathode, leading to photocatalytic activities are improved. The results have recorded a significant increase in the photocurrent density from 2.3µAcm-2of TiO2to approximately 16.3µAcm-2of MoS2/TiO2/Au NPs. This work unveils a promising route to enhance the visible light adsorption and charge transfer in photo-electrode of the PEC cells by combining two-dimensional materials with metal NPs.

20.
BMC Infect Dis ; 24(1): 163, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321395

RESUMO

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known. METHODS: We included 659 individuals aged [Formula: see text] years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl-Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally. RESULTS: Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden's Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively. CONCLUSION: Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM. Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.


Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Meníngea , Humanos , Idoso , Tuberculose Meníngea/diagnóstico , Análise de Classes Latentes , Teorema de Bayes , Sensibilidade e Especificidade , Convulsões
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