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1.
Adv Mater ; : e2406345, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39246122

RESUMO

Photo-transduction of solid-state optoelectronics occurs in semiconductors or their interfaces. Considering the confined active area and interfacial capacitance of solid-state materials, solid-state optoelectronics faces inherent limitations in photo-transduction, especially for bionic vision, and the performance is lower than that of living systems. For example, a photoreceptor generates pA-level photocurrent when absorbing a single photon. Here, a liquid-solid dual-state phototransistor is demonstrated, in which photo-transduction and modulation take place at the microporous interface between semiconductors and water, mimicking principles of the photoreceptor. When operating in the water, an orderly stacked photo-harvesting covalent organic framework layer generates supercapacitively photogating modulation of the channel conductivity via a dual-state interface, achieving responsivity of 4.6 × 1010 A W-1 and detectivity of 1.62 × 1016 Jones at room temperature, several orders of magnitude higher than other photodetectors. Such bio-inspired dual-state optoelectronics enables high-contrast scotopic neuromorphic imaging with responsivity greater than photoreceptors, holding promise for constructing optoelectronic systems with performance beyond conventional solid-state optoelectronics.

2.
Cell Insight ; 3(5): 100193, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39183739

RESUMO

Human immunodeficiency virus (HIV) continues to be a significant global health challenge despite decades of research and advances in treatment. Substantial gaps in our understanding of the mechanisms of HIV pathogenesis and the host immune responses still exist. The interaction between HIV and these immune responses is pivotal in the disease progression to acquired immunodeficiency syndrome (AIDS). Recently, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome has emerged as a crucial factor in orchestrating innate immune responses to HIV infection and exerting a substantial impact on viral pathogenesis. CARD8 restricts viral replication by detecting the activity of HIV protease. Conversely, it also contributes to the depletion of CD4+ T cells, a key feature of disease progression towards AIDS. The purpose of this review is to summarize the role of the CARD8 inflammasome in HIV pathogenesis, delving into its mechanisms of action and potential implications for the development of therapeutic strategies.

3.
Sci Total Environ ; 950: 175308, 2024 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-39117198

RESUMO

The extensive use of plastic products has resulted in a significant influx of microplastics into aquatic ecosystems, particularly in highly urbanized areas and their associated river environments. However, the specific pathways and quantities through which these microplastics enter the river environment are still unclear, which poses a challenge in developing effective measures to mitigate their sources. In this paper, the spatiotemporal variations of microplastics from different sources in highly urbanized rivers within the Shenzhen Bay watershed were investigated through field sampling, experimental and statistical analysis, and the measures of microplastic reduction were discussed. The observation results exhibited a negative logarithmic correlation between the abundance of microplastics in river water and monthly rainfall (R = 0.994, MSE = 0.051, p < 0.05). When the monthly rainfall was <6 mm, the abundance of microplastics was absolutely dependent on point sources. While the rainfall exceeded 470 mm, the abundance was absolutely predominantly influenced by nonpoint source microplastics. The annual load of microplastics from the watershed was 5.39 × 1012 items, of which 61.6 % originated from point sources. Among the microplastics from point sources, 92.1 % were derived from fibers generated by textile washing. Fragmented microplastics (41.9 %) were the most common type of microplastics from nonpoint sources, primarily originating from the disintegration and weathering of disposable plastics. In the future, there is an expectation to reduce the microplastic load in the watershed to 15.9 % of the total by improving sewage treatment processes and infrastructure. This study can provide scientific guidance for environmental planning and serve as a warning regarding the impact of microplastics on ecosystems in urbanized areas.

4.
J Phys Chem C Nanomater Interfaces ; 128(26): 11014-11023, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38983597

RESUMO

Crucial to the performance of devices based on organic molecules is an understanding of how the substrate-molecule interface influences both structural and electronic properties of the molecular layers. Within this context we studied the self-assembly of an alkoxy-triphenylene derived electron donor (HAT) in the monolayer regime on graphene/Ni(111). The molecules assembled into a close-packed hexagonal network commensurate with the graphene layer. Despite the commensurate structure, the HAT molecules only had a weak, physisorptive interaction with the substrate as pointed out by the photoelectron spectroscopy data. We discuss these findings in view of our recent reports for HAT adsorbed on Ag(111) and graphene/Ir(111). For all three substrates HAT adopts a similar close-packed hexagonal structure commensurate with the substrate while being physisorbed. The ionization potential is equal for all three substrates, supporting weak molecule-substrate interactions. These findings are remarkable, as commensurate overlayers usually only form at strongly interacting interfaces. We discuss potential reasons for this particular behavior of HAT which clearly sets itself apart from most studied molecule-substrate systems. In particular, these are the relatively weak but flexible intermolecular interactions, the molecular symmetry matching that of the substrate, and the comparatively weak but directional molecule-substrate interactions.

5.
6.
mBio ; 15(5): e0034824, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38530034

RESUMO

A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization per se does not completely block reverse transcription. Surprisingly, due to the combined effects of enhanced reverse transcription and defects in nuclear entry, two separate CA mutants that form hyperstable cores induced innate immune sensing more potently than destabilizing CA mutations. At low concentrations that allowed the accumulation of reverse transcription products, CA-targeting compounds GS-CA1 and lenacapavir measurably impacted CA lattice stability in cells and modestly enhanced innate immune sensing of HIV. Interestingly, innate immune activation observed with viruses containing unstable cores was abolished by low doses of lenacapavir. Innate immune activation observed with both hyperstable and unstable CA mutants was dependent on the cGAS-STING DNA-sensing pathway and reverse transcription. Overall, our findings demonstrate that CA lattice stability and reverse transcription are finely balanced to support reverse transcription and minimize cGAS-STING-mediated sensing of the resulting viral DNA. IMPORTANCE: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.


Assuntos
Proteínas do Capsídeo , Capsídeo , HIV-1 , Imunidade Inata , Proteínas de Membrana , Nucleotidiltransferases , Transcrição Reversa , HIV-1/genética , HIV-1/imunologia , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/imunologia , Capsídeo/metabolismo , Capsídeo/imunologia , Transdução de Sinais , Células HEK293 , Infecções por HIV/virologia , Infecções por HIV/imunologia , Infecções por HIV/genética , RNA Viral/genética , RNA Viral/metabolismo
7.
Thorac Cancer ; 15(12): 947-964, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38480505

RESUMO

BACKGROUND: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)-based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. METHODS: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre- and delta-radiomic features were extracted from enhanced CT images. LASSO-Cox regression was used to select the radiomics signatures most associated with progression-free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C-index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune-related hematological parameters was analyzed by spearman correlation analysis. RESULTS: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre- or delta-Rad-score. The AUC of the delta-radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta-radiomic features are significantly correlated with delta-ALC (absolute lymphocyte count) and delta-NLR (neutrophil-to-lymphocyte ratio). CONCLUSIONS: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Baço , Humanos , Masculino , Feminino , Prognóstico , Carcinoma de Células Escamosas do Esôfago/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Idoso , Tomografia Computadorizada por Raios X/métodos , Adulto , Radiômica
8.
Cell ; 187(5): 1223-1237.e16, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38428396

RESUMO

While CD4+ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4+ depletion is delayed despite high viremia. Finally, we discovered loss-of-function mutations in CARD8 from "natural hosts," which may explain the peculiarly non-pathogenic nature of these infections. Our study suggests that CARD8 drives CD4+ T cell depletion during pathogenic HIV/SIV infections.


Assuntos
Infecções por HIV , Inflamassomos , Síndrome de Imunodeficiência Adquirida dos Símios , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Progressão da Doença , Infecções por HIV/patologia , Inflamassomos/metabolismo , Proteínas de Neoplasias/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Vírus da Imunodeficiência Símia/fisiologia , Viremia , HIV/fisiologia
10.
Sci Rep ; 14(1): 1778, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245572

RESUMO

Protein kinase C substrate 80K-H (PRKCSH) plays a crucial role in the protein N-terminal glycosylation process, with emerging evidence implicating its involvement in tumorigenesis. To comprehensively assess PRKCSH's significance across cancers, we conducted a pan-cancer analysis using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE). We assessed aberrant PRKCSH mRNA and protein expression, examined its prognostic implications, and identified correlations with clinical features, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immunity across cancer types. We explored PRKCSH gene alterations, DNA methylation, and their impact on patient prognosis. Gene Set Enrichment Analysis (GSEA) and single-cell analysis revealed potential biological roles. Additionally, we investigated drug susceptibility and conducted Connectivity Map (Cmap) analysis. Key findings revealed that PRKCSH exhibited overexpression in most tumors, with a significant association with poor overall survival (OS) in six cancer types. Notably, PRKCSH expression demonstrated variations across disease stages, primarily increasing in advanced stages among eleven tumor types. Moreover, PRKCSH exhibited significant correlations with TMB in five cancer categories, MSI in eight, and displayed associations with immune cell populations in pan-cancer analysis. Genetic variations in PRKCSH were identified across 26 tumor types, suggesting favorable disease-free survival. Furthermore, PRKCSH methylation displayed a significant negative correlation with its expression in 27 tumor types, with a marked decrease compared to normal tissues in ten tumors. Cmap predicted 24 potential therapeutic small molecules in over four cancer types. This study highlights that PRKCSH, as a potential oncogene, may be a promising prognostic marker and therapeutic target of immunotherapy for a range of malignancies.


Assuntos
Neoplasias , Humanos , Prognóstico , Neoplasias/genética , Oncogenes , Carcinogênese , Instabilidade de Microssatélites , Biomarcadores , Proteínas de Ligação ao Cálcio , Glucosidases
11.
Nat Protoc ; 19(2): 340-373, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38001366

RESUMO

Crystalline polymer materials, e.g., hyper-crosslinked polystyrene, conjugate microporous polymers and covalent organic frameworks, are used as catalyst carriers, organic electronic devices and molecular sieves. Their properties and applications are highly dependent on their crystallinity. An efficient polymerization strategy for the rapid preparation of highly or single-crystalline materials is beneficial not only to structure-property studies but also to practical applications. However, polymerization usually leads to the formation of amorphous or poorly crystalline products with small grain sizes. It has been a challenging task to efficiently and precisely assemble organic molecules into a single crystal through polymerization. To address this issue, we developed a supercritically solvothermal method that uses supercritical carbon dioxide (sc-CO2) as the reaction medium for polymerization. Sc-CO2 accelerates crystal growth due to its high diffusivity and low viscosity compared with traditional organic solvents. Six covalent organic frameworks with different topologies, linkages and crystal structures are synthesized by this method. The as-synthesized products feature polarized photoluminescence and second-harmonic generation, indicating their high-quality single-crystal nature. This method holds advantages such as rapid growth rate, high productivity, easy accessibility, industrial compatibility and environmental friendliness. In this protocol, we provide a step-by-step procedure including preparation of monomer dispersion, polymerization in sc-CO2, purification and characterization of the single crystals. By following this protocol, it takes 1-5 min to grow sub-mm-sized single crystals by polymerization. The procedure takes ~4 h from preparation of monomer dispersion and polymerization in sc-CO2 to purification and drying of the product.


Assuntos
Estruturas Metalorgânicas , Dióxido de Carbono , Polimerização , Polímeros , Cristalização
12.
J Cancer Res Clin Oncol ; 149(19): 17285-17296, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37815661

RESUMO

BACKGROUND: Bile acids (BA) are important metabolites and serve as signaling molecules, which are involve in multiple cancer-related signaling pathways. METHODS: A validated LC-MS/MS approach was applied in a case-control study with 220 non-small cell lung cancer (NSCLC) patients and 244 matched healthy controls. The concentrations of seven common types of BAs in serum were determined and compared. Subgroup analyses based on demographic factor, lifestyle, pathologic types and tumor stage were conducted. Machine learning analysis was performed for NSCLC classification. RESULTS: Serum levels of primary BAs, including cholic acid (CA), taurocholic acid (TCA) and glycocholic acid (GCA), were upregulated, while lithocholic acid (LCA), a type of secondary BA, was downregulated in NSCLC patients compared with healthy controls in overall analysis. Higher level of chenodeoxycholic acid (CDCA) and lower level of ursodeoxycholic acid (UDCA) were observed in female, elder, overweight patients, as well as patients without alcohol use in comparison with controls. CDCA and CA levels were higher only in lung adenocarcinoma (LUAD), and UDCA and DCA levels were lower only in squamous cell carcinoma (LUSC), while the concentrations of TCA, GCA, and LCA were altered prevalently in LUAD and LUSC patients. For discrimination of NSCLC from healthy people, the area under the receiver operating characteristics (ROC) curve of the models through support vector machine (SVM) approach was 0.91 (95% CI 0.88-0.94) in the training set and 0.84 (95% CI 0.78-0.91) in the validation set, respectively. CONCLUSIONS: Serum BAs were altered in NSCLC patients compared with controls, among which primary BAs were elevated and secondary BAs were decreased. Moreover, distinct patterns of BA alterations were revealed between LUAD patients and LUSC patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Casos e Controles , Cromatografia Líquida , Neoplasias Pulmonares/tratamento farmacológico , Espectrometria de Massas em Tandem , Ácidos e Sais Biliares
13.
Proteomics ; 23(20): e2300140, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37474491

RESUMO

Aberrant serum N-glycan profiles have been observed in multiple cancers including non-small-cell lung cancer (NSCLC), yet the potential of N-glycans in the early diagnosis of NSCLC remains to be determined. In this study, serum N-glycan profiles of 275 NSCLC patients and 309 healthy controls were characterized by MALDI-TOF-MS. The levels of serum N-glycans and N-glycosylation patterns were compared between NSCLC and control groups. In addition, a panel of N-glycan biomarkers for NSCLC diagnosis was established and validated using machine learning algorithms. As a result, a total of 54 N-glycan structures were identified in human serum. Compared with healthy controls, 29 serum N-glycans were increased or decreased in NSCLC patients. N-glycan abundance in different histological types or clinical stages of NSCLC presented differentiated changes. Furthermore, an optimal biomarker panel of eight N-glycans was constructed based on logistic regression, with an AUC of 0.86 in the validation set. Notably, this model also showed a desirable capacity in distinguishing early-stage patients from healthy controls (AUC = 0.88). In conclusion, our work highlights the abnormal N-glycan profiles in NSCLC and provides supports potential application of N-glycan biomarker panel in clinical NSCLC detection.

14.
J Hazard Mater ; 458: 131871, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37348376

RESUMO

Cyanide tailings are the bulk solid waste generated by the production processes of gold mines. Since the highly toxicity of cyanide affects its disposal and comprehensive utilization, a decyanation treatment is needed. However, wide-ranging industrial uses of the current decyanation methods are restricted due to the treatment effects and costs. Based on the natural degradation method, the cyanide treatment effect was enhanced by raising the treatment temperature, increasing the ultraviolet (UV) irradiation and turning the pile periodically. Using the Arrhenius equation, the activation energies of the cyanide hydrolysis reactions were calculated as 52.22 kJ/mol and 34.59 kJ/mol for heating alone and for heating combined with UV irradiation, respectively. At 60 â„ƒ, the cyanide tailings reached the discharge standard (leachate, total cyanide (CNt)< 5 mg/L) after 8 h of treatment. Moreover, after adding UV irradiation (with an intensity of 120 µW/cm2) and a hydrogen peroxide spray (spraying intensity, 2 mL/kg) to the above conditions and shortening the treatment time to 7 h, the cyanide tailings reached the standard for use in building materials (leachate, CNt <0.5 mg/L). Based on these results, UV irradiation, ventilation, spraying and pile-turning were integrated into the solar drying room to form an enhanced natural degradation system, which was applied in the semi-industrial scale treatment of the cyanide tailings. The results showed that the cyanide tailings consistently met the standards for discharge and use in building materials, successfully verified the conditions and effects of the laboratory treatment, and reduced the treatment cost by more than 50 %.

15.
Arch Anim Breed ; 66(1): 131-139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124941

RESUMO

We explore the relationship between the melanophilin (MLPH) gene and quail plumage color and provide a reference for subsequent quail plumage color breeding. In this experiment, real-time quantitative PCR (RT-qPCR) technology was used to analyze the relative mRNA expression levels of Korean quail (maroon) and Beijing white quail embryos at different developmental stages. Two single-nucleotide polymorphisms (SNPs) in the MLPH gene were screened based on the RNA-sequencing (RNA-Seq) data of skin tissues of Korean quail and Beijing white quail during the embryonic stage. Kompetitive allele-specific PCR (KASP) technology was used for genotyping in the resource population, and correlation analysis was carried out with the plumage color traits of quail. Finally, bioinformatics was used to predict the effects of these two SNPs on the structure and function of the encoded protein. The results showed that the expression level of the MLPH gene during embryonic development of Beijing white quail was significantly higher than that of Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (CC, CA and AA) of the Beijing white quail at the c.1807C  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). The frequency distribution of the three genotypes (GG, GA and AA) of the Beijing white quail at the c.2129G  >  A mutation site was significantly different from that of the Korean quail ( P < 0.01 ). And there was a significant correlation between the c.1807C  >  A mutation site and the white plumage phenotype. Bioinformatics showed that SNP1 (c.1807C  >  A) was a neutral mutation and that SNP2 (c.2129G  >  A) was a deleterious mutation. The prediction of protein conservation showed that the mutation sites of coding proteins R603S and G710D caused by SNP1 (c.1807C  >  A) and SNP2 (c.2129G  >  A) were highly conserved.

16.
Interdiscip Sci ; 15(3): 405-418, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37247186

RESUMO

DNA methylation-based precision tumor early diagnostics is emerging as state-of-the-art technology that could capture early cancer signs 3 ~ 5 years in advance, even for clinically homogenous groups. Presently, the sensitivity of early detection for many tumors is ~ 30%, which needs significant improvement. Nevertheless, based on the genome-wide DNA methylation data, one could comprehensively characterize tumors' entire molecular genetic landscape and their subtle differences. Therefore, novel high-performance methods must be modeled by considering unbiased information using excessively available DNA methylation data. To fill this gap, we have designed a computational model involving a self-attention graph convolutional network and multi-class classification support vector machine to identify the 11 most common cancers using DNA methylation data. The self-attention graph convolutional network automatically learns key methylation sites in a data-driven way. Then, multi-tumor early diagnostics is realized by training a multi-class classification support vector machine based on the selected methylation sites. We evaluated our model's performance through several data sets of experiments, and our results demonstrate the effectiveness of the selected key methylation sites, which are highly relevant for blood diagnosis. The pipeline of the self-attention graph convolutional network based computational framework.


Assuntos
Metilação de DNA , Neoplasias , Humanos , Metilação de DNA/genética , Neoplasias/diagnóstico , Neoplasias/genética , Processamento de Proteína Pós-Traducional , Máquina de Vetores de Suporte
17.
J Am Chem Soc ; 145(18): 10035-10044, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37097713

RESUMO

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.


Assuntos
Técnicas Biossensoriais , Líquidos Corporais , Animais , Camundongos , Técnicas Biossensoriais/métodos , Aldeído Pirúvico , Saliva , Transistores Eletrônicos
18.
Adv Immunol ; 157: 59-100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37061288

RESUMO

The biggest challenge to immune control of HIV infection is the rapid within-host viral evolution, which allows selection of viral variants that escape from T cell and antibody recognition. Thus, it is impossible to clear HIV infection without targeting "immutable" components of the virus. Unlike the adaptive immune system that recognizes cognate epitopes, the CARD8 inflammasome senses the essential enzymatic activity of the HIV-1 protease, which is immutable for the virus. Hence, all subtypes of HIV clinical isolates can be recognized by CARD8. In HIV-infected cells, the viral protease is expressed as a subunit of the viral Gag-Pol polyprotein and remains functionally inactive prior to viral budding. A class of anti-HIV drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs), can promote Gag-pol dimerization and subsequent premature intracellular activation of the viral protease. NNRTI treatment triggers CARD8 inflammasome activation, which leads to pyroptosis of HIV-infected CD4+ T cells and macrophages. Targeting the CARD8 inflammasome can be a potent and broadly effective strategy for HIV eradication.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Inflamassomos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Proteínas de Neoplasias/farmacologia , Proteínas de Neoplasias/uso terapêutico , Proteínas Adaptadoras de Sinalização CARD
19.
Methods Mol Biol ; 2641: 67-79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37074642

RESUMO

The pattern recognition receptor CARD8 is an inflammasome sensor for intracellular HIV-1 protease activity. Previously, the only method for studying the CARD8 inflammasome has been through utilizing DPP8/DPP9 inhibitors including Val-boroPro (VbP) to modestly and nonspecifically activate the CARD8 inflammasome. The identification of HIV-1 protease as a target for sensing by CARD8 has opened the door for a new method of studying the underlying mechanism of CARD8 inflammasome activation. Additionally, triggering the CARD8 inflammasome offers a promising strategy for reducing HIV-1 latent reservoirs. Here we describe the methods to study CARD8 sensing of HIV-1 protease activity through non-nucleoside reverse transcriptase inhibitor (NNRTI)-mediated pyroptosis of HIV-1-infected immune cells and through an HIV and CARD8 co-transfection model.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Inflamassomos , Inflamassomos/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Protease de HIV
20.
Pathogens ; 12(3)2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36986405

RESUMO

Golden snub-nosed monkeys (Rhinopithecus roxellanae) belong to Class A, the highest level of endangered primate species. Exploring the infection status of potential pathogens in golden snub-nosed monkeys is important for controlling associated diseases and protecting this species. The objective of this study was to investigate the seroprevalence for a number of potential pathogens and the prevalence of fecal adenovirus and rotavirus. A total of 283 fecal samples were collected from 100 golden snub-nosed monkeys in December 2014, June 2015, and January 2016; 26 blood samples were collected from 26 monkeys in June 2014, June 2015, January 2016 and November 2016 at Shennongjia National Reserve in Hubei, China. The infection of 11 potential viral diseases was examined serologically using an Indirect Enzyme-linked Immunosorbent Assay (iELISA) and Dot Immunobinding Assays (DIA), while the whole blood IFN-γ in vitro release assay was used to test tuberculosis (TB). In addition, fecal Adenovirus and Rotavirus were detected using Polymerase Chain Reaction (PCR). As a result, the Macacine herpesvirus-1 (MaHV-1), Golden snub-nosed monkey cytomegalovirus (GsmCMV), Simian foamy virus (SFV) and Hepatitis A virus (HAV) were detected with the seroprevalence of 57.7% (95% CI: 36.9, 76.6), 38.5% (95% CI: 20.2, 59.4), 26.9% (95% CI: 11.6, 47.8), and 7.7% (95% CI: 0.0, 84.2), respectively. Two fecal samples tested positive for Adenovirus (ADV) by PCR, with a prevalence of 0.7% (95% CI: 0.2, 2.5), and further, the amplification products were sequenced. Phylogenetic analysis revealed that they belonged to the HADV-G group. However, other pathogens, such as Coxsackievirus (CV), Measles virus (MeV), Rotavirus (RV), Simian immunodeficiency virus (SIV), Simian type D retroviruses (SRV), Simian-T-cell lymphotropic virus type 1 (STLV-1), Simian varicella virus (SVV), Simian virus 40 (SV40) and Mycobacterium tuberculosis complex (TB) were negative in all samples. In addition, a risk factor analysis indicated that the seroprevalence of MaHV-1 infection was significantly associated with old age (≥4 years). These results have important implications for understanding the health status and conservation of the endangered golden snub-nosed monkey population at Shennongjia Nature Reserve.

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