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1.
J Mater Chem B ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995372

RESUMO

Hydrophilic peptides (HPs) play a critical role in the pathogenesis of hepatocellular carcinoma (HCC). However, the comprehensive and in-depth high-throughput analysis of specific changes in HPs associated with HCC remains unrealized, due to the complex nature of biological fluids and the challenges of mining complex patterns in large data sets. The clinical diagnosis of HCC still lacks a non-destructive and accurate classification method, given the limited specificity of widely used biomarkers. To address these challenges, we have established a multifunctional platform that integrates artificial intelligence computation, hydrophilic interaction extraction of HPs, and MALDI-MS testing. This platform aims to achieve highly sensitive HP fingerprinting for accurate diagnosis of HCC. The method not only facilitates efficient detection of HPs, but also achieves a remarkable 100.00% diagnostic accuracy for HCC in a test cohort, supported by machine learning algorithms. By constructing a panel of HPs with 10 characteristic features, we achieved 98% accuracy in the test cohort for rapid diagnosis and identified 62 HPs deeply involved in pathways related to liver diseases. This integrated strategy provides new research directions for future biomarker studies as well as early diagnosis and individualized treatment of HCC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38972728

RESUMO

BACKGROUND AND AIM: There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI. METHODS: Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort. RESULTS: A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035). CONCLUSION: This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.

3.
Respir Res ; 25(1): 254, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907347

RESUMO

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.


Assuntos
Antituberculosos , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas , Metabolômica , Humanos , Antituberculosos/efeitos adversos , Masculino , Metabolômica/métodos , Feminino , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estudos Longitudinais , Adulto , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos Prospectivos , Valor Preditivo dos Testes , Tuberculose/tratamento farmacológico , Tuberculose/sangue , Tuberculose/metabolismo , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo
4.
J Mater Chem B ; 12(27): 6668-6677, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38884176

RESUMO

This study presented a nanoparticle-enhanced aptamer-recognizing homogeneous detection system combined with a portable instrument (NASPI) to quantify lipoarabinomannan (LAM). This system leveraged the high binding affinity of aptamers, the high sensitivity of nanoparticle cascade amplification, and the stabilization effect of dual stabilizers (fructose and histone), and used probe-Cu2+ to achieve LAM detection at concentrations ranging from 10 ag mL-1 to 100 fg mL-1, with a limit of detection of 3 ag mL-1 using a fluorometer. It can also be detected using an independently developed handheld fluorometer or the red-green-blue (RGB) camera of a smartphone, with a minimum detection concentration of 10 ag mL-1. We validated the clinical utility of the biosensor by testing the LAM in the urine of patients. Forty urine samples were tested, with positive LAM results in the urine of 18/20 tuberculosis (TB) cases and negative results in the urine of 6/10 latent tuberculosis infection cases and 10/10 non-TB cases. The assay results revealed a 100% specificity and a 90% sensitivity, with an area under the curve of 0.9. We believe that the NASPI biosensor can be a promising clinical tool with great potential to convert LAM into clinical indicators for TB patients.


Assuntos
Cobre , Frutose , Lipopolissacarídeos , Nanopartículas Metálicas , Smartphone , Tuberculose , Cobre/química , Humanos , Tuberculose/diagnóstico , Tuberculose/urina , Nanopartículas Metálicas/química , Lipopolissacarídeos/urina , Frutose/urina , DNA/química , Técnicas Biossensoriais , Fluorometria
5.
Anal Chem ; 96(26): 10705-10713, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38910291

RESUMO

Circulating tumor cells (CTCs) serve as important biomarkers in the liquid biopsy of hepatocellular carcinoma (HCC). Herein, a homogeneous dual fluorescence indicators aptasensing strategy is described for CTCs in HCC, with the core assistance of a steric hindrance-mediated enzymatic reaction. CTCs in the sample could specifically bind to a 5'-biotin-modified glypican-3 (GPC3) aptamer and remove the steric hindrance formed by the biotin-streptavidin system. This influences the efficiency of the terminal deoxynucleotidyl transferase enzymatic reaction. Then, methylene blue (MB) was introduced to react with the main product poly cytosine (polyC) chain, and trivalent cerium ion (Ce3+) was added to react with the byproduct pyrophosphate to form fluorescent pyrophosphate cerium coordination polymeric nanoparticles. Finally, the CTCs were quantified by dual fluorescence indicators analysis. Under optimized conditions, the linear range was 5 to 104 cells/mL, and the limits of detection reached 2 cells/mL. Then, 40 clinical samples (15 healthy and 25 HCC patients) were analyzed. The receiver operating characteristic curve analysis revealed an area under the curve of 0.96, a sensitivity of 92%, and a specificity of 100%. Therefore, this study established a sensitive and accurate CTCs sensing system for clinical HCC patients, promoting early tumor diagnosis.


Assuntos
Aptâmeros de Nucleotídeos , Carcinoma Hepatocelular , Corantes Fluorescentes , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Células Neoplásicas Circulantes/patologia , Células Neoplásicas Circulantes/metabolismo , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Glipicanas/metabolismo , Técnicas Biossensoriais
6.
Talanta ; 277: 126310, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38815319

RESUMO

The sensitive and accurate detection of target microRNA is especially important for the diagnosis, staging, and treatment of hepatocellular carcinoma (HCC). Herein, we report a simple strand displacement and CRISPR-Cas12a amplification strategy with nanozymes as a signal reporter for the binary visual and colorimetric detection of the HCC related microRNA. Pt@Au nanozymes with excellent peroxidase enzyme activity were prepared and linked to magnetic beads via a single-stranded DNA (ssDNA) linker. The target microRNA was designed to trigger strand displacement amplification and release a DNA promoter to activate the CRISPR-Cas12a system. The activated CRISPR-Cas12a system efficiently cleaved the linker ssDNA and released Pt@Au nanozymes from magnetic beads to induce the colorimetric reaction of 3,3',5,5'-tetramethylbenzidine. The strand displacement amplification converted the single microRNA input into abundant DNA promoter output, which improved the detection sensitivity by over two orders of magnitude. Through integration of strand displacement amplification and the nanozyme-mediated CRISPR-Cas12a system, limits of detection of 0.5 pM and 10 pM for miRNA-21 were achieved with colorimetric and visual readouts, respectively. The proposed strategy can achieve accurate quantitative detection of miRNA-21 in the range from 1 pM to 500 pM. The detection results for miRNA-21 using both colorimetric and visual readouts were validated in 40 clinical serum samples. Significantly, the proposed strategy achieved visual HCC diagnosis with the naked eye and could distinguish distinct Barcelona clinical HCC stages by colorimetric detection, showing good application prospects for sensitive and facile point-of-care testing for HCC.

7.
Emerg Microbes Infect ; 13(1): 2356143, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38767202

RESUMO

ABSTRACTImproved sanitation, increased access to health care, and advances in preventive and clinical medicine have reduced the mortality and morbidity rates of several infectious diseases. However, recent outbreaks of several emerging infectious diseases (EIDs) have caused substantial mortality and morbidity, and the frequency of these outbreaks is likely to increase due to pathogen, environmental, and population effects driven by climate change. Extreme or persistent changes in temperature, precipitation, humidity, and air pollution associated with climate change can, for example, expand the size of EID reservoirs, increase host-pathogen and cross-species host contacts to promote transmission or spillover events, and degrade the overall health of susceptible host populations leading to new EID outbreaks. It is therefore vital to establish global strategies to track and model potential responses of candidate EIDs to project their future behaviour and guide research efforts on early detection and diagnosis technologies and vaccine development efforts for these targets. Multi-disciplinary collaborations are demanding to develop effective inter-continental surveillance and modelling platforms that employ artificial intelligence to mitigate climate change effects on EID outbreaks. In this review, we discuss how climate change has increased the risk of EIDs and describe novel approaches to improve surveillance of emerging pathogens that pose the risk for EID outbreaks, new and existing measures that could be used to contain or reduce the risk of future EID outbreaks, and new methods to improve EID tracking during further outbreaks to limit disease transmission.


Assuntos
Mudança Climática , Doenças Transmissíveis Emergentes , Humanos , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Animais , Surtos de Doenças/prevenção & controle
8.
Small ; : e2401022, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809081

RESUMO

Renewable energy technologies, such as water splitting, heavily depend on the oxygen evolution reaction (OER). Nanolaminated ternary compounds, referred to as MAX phases, show great promise for creating efficient electrocatalysts for OER. However, their limited intrinsic oxidative resistance hinders the utilization of conductivity in Mn+1Xn layers, leading to reduced activity. In this study, a method is proposed to improve the poor inoxidizability of MAX phases by carefully adjusting the elemental composition between Mn+1Xn layers and single-atom-thick A layers. The resulting Ta2FeC catalyst demonstrates superior performance compared to conventional Fe/C-based catalysts with a remarkable record-low overpotential of 247 mV (@10 mA cm-2) and sustained activity for over 240 h. Notably, during OER processing, the single-atom-thick Fe layer undergoes self-reconstruction and enrichment from the interior of the Ta2FeC MAX phase toward its surface, forming a Ta2FeC@Ta2C@FeOOH heterostructure. Through density functional theory (DFT) calculations, this study has found that the incorporation of Ta2FeC@Ta2C not only enhances the conductivity of FeOOH but also reduces the covalency of Fe─O bonds, thus alleviating the oxidation of Fe3+ and O2-. This implies that the Ta2FeC@Ta2C@FeOOH heterostructure experiences less lattice oxygen loss during the OER process compared to pure FeOOH, leading to significantly improved stability. These results highlight promising avenues for further exploration of MAX phases by strategically engineering M- and A-site engineering through multi-metal substitution, to develop M2AX@M2X@AOOH-based catalysts for oxygen evolution.

9.
Mol Cancer ; 23(1): 71, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575922

RESUMO

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.


Assuntos
Carcinogênese , Neoplasias , Humanos , Transformação Celular Neoplásica/genética , Morte Celular , Nutrientes , Oxigênio , Apoptose
10.
Small Methods ; : e2400095, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466131

RESUMO

Efficient diagnosis of mycobacterial infections can effectively manage and prevent the transmission of infectious diseases. Unfortunately, existing diagnostic strategies are challenged by long assay times, high costs, and highly specialized expertise to distinguish between pulmonary tuberculosis (PTB) and nontuberculous mycobacterial pulmonary diseases (NTM-PDs). Herein, in this study, an optimized 3D paper-based analytical device (µPAD) is incorporated with a closed lateral flow (LF) strip into a loop-mediated isothermal amplification (LAMP) device (3D-µPAD-LF-LAMP) for rapid, low-cost, and visual detection of pathogenic mycobacteria. The platform's microfluidic feature enhanced the nucleic acid amplification, thereby reducing the costs and time as compared to boiling, easyMAG, and QIAGEN techniques. Moreover, the LF unit is specifically designed to minimize aerosol contamination for a user-friendly and visual readout. 3D-µPAD-LF-LAMP is optimized and assessed using standard strains, demonstrating a limit of detection (LOD) down to 10 fg reaction-1 . In a cohort of 815 patients, 3D-µPAD-LF-LAMP displays significantly better sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy than conventional bacterial culture and Xpert techniques. Collectively, 3D-µPAD-LF-LAMP demonstrates enhanced accessibility, efficiency, and practicality for the diagnosis of multiple pathogenic mycobacteria, which can be applied across diverse clinical settings, thereby ultimately improving public health outcomes.

11.
MedComm (2020) ; 5(3): e487, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469547

RESUMO

Deep learning, transforming input data into target prediction through intricate network structures, has inspired novel exploration in automated diagnosis based on medical images. The distinct morphological characteristics of chest abnormalities between drug-resistant tuberculosis (DR-TB) and drug-sensitive tuberculosis (DS-TB) on chest computed tomography (CT) are of potential value in differential diagnosis, which is challenging in the clinic. Hence, based on 1176 chest CT volumes from the equal number of patients with tuberculosis (TB), we presented a Deep learning-based system for TB drug resistance identification and subtype classification (DeepTB), which could automatically diagnose DR-TB and classify crucial subtypes, including rifampicin-resistant tuberculosis, multidrug-resistant tuberculosis, and extensively drug-resistant tuberculosis. Moreover, chest lesions were manually annotated to endow the model with robust power to assist radiologists in image interpretation and the Circos revealed the relationship between chest abnormalities and specific types of DR-TB. Finally, DeepTB achieved an area under the curve (AUC) up to 0.930 for thoracic abnormality detection and 0.943 for DR-TB diagnosis. Notably, the system demonstrated instructive value in DR-TB subtype classification with AUCs ranging from 0.880 to 0.928. Meanwhile, class activation maps were generated to express a human-understandable visual concept. Together, showing a prominent performance, DeepTB would be impactful in clinical decision-making for DR-TB.

12.
MedComm (2020) ; 5(3): e508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463395

RESUMO

Neuro-COVID, a condition marked by persistent symptoms post-COVID-19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS-CoV-2 invasion in the CNS, the increasing incidence of Neuro-COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro-COVID patients. Furthermore, notable differences emerged between RNA-CSF-positive and negative patients, encompassing aspects such as blood-brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS-CoV-2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro-COVID to unravel the complexities of this relationship, and pivotal in addressing the long-term consequences of COVID-19 on neurological health.

13.
ACS Appl Mater Interfaces ; 16(12): 14510-14519, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488618

RESUMO

Interferon-γ (IFN-γ) release assays (IGRAs) are constrained by the limited diagnostic performance of a single indicator and the excessive Mycobacterium tuberculosis (Mtb) antigen stimulation time. This study presents a simultaneous, homogeneous, rapid, and ultrasensitive fluorescence quantification strategy for IFN-γ and IFN-γ-induced protein 10 (IP-10). This method relies on the high-affinity binding of aptamers to IFN-γ and IP-10, the enzyme-free catalytic hairpin assembly reaction, and the heightened sensitivity of CdTe quantum dots to Ag+ and hairpin structure C-Ag+-C and carbon dots to Hg2+ and hairpin structure T-Hg2+-T. Under optimized conditions, the selectivity of IFN-γ and IP-10 was excellent, with a linear range spanning from 1 to 100 ag/mL and low limits of detection of 0.3 and 0.5 ag/mL, respectively. Clinical practicality was confirmed through testing of 57 clinical samples. The dual-indicator combination detection showed 92.8% specificity and 93.1% sensitivity, with an area under the curve of 0.899, representing an improvement over the single-indicator approach. The Mtb antigen stimulation time was reduced to 8 h for 6/7 clinical samples. These findings underscore the potential of our approach to enhance the efficiency and performance of a tuberculosis (TB) clinical diagnosis.


Assuntos
Compostos de Cádmio , Mercúrio , Mycobacterium tuberculosis , Ácidos Nucleicos , Pontos Quânticos , Tuberculose , Humanos , Quimiocina CXCL10 , Ensaio de Imunoadsorção Enzimática/métodos , Telúrio , Tuberculose/diagnóstico , Interferon gama/metabolismo , Antígenos
14.
Food Chem ; 447: 139018, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38503067

RESUMO

Developing an accurate, cost-effective, reliable, and stable glucose detection sensor for the food industry poses a significant yet challenging endeavor. Herein, we present a silver nanoparticle-decorated titanium dioxide nanoribbon array on titanium plate (Ag@TiO2/TP) as an efficient electrode for non-enzymatic glucose detection in alkaline environments. Electrochemical evaluations of the Ag@TiO2/TP electrode reveal a broad linear response range (0.001 mM - 4 mM), high sensitivity (19,106 and 4264 µA mM-1 cm-2), rapid response time (6 s), and a notably low detection limit (0.18 µM, S/N = 3). Moreover, its efficacy in measuring glucose in beverage samples shows its practical applicability. The impressive performance and structural benefits of the Ag@TiO2/TP electrode highlight its potential in advancing electrochemical sensors for small molecule detection.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Nanotubos de Carbono , Nanopartículas Metálicas/química , Técnicas Eletroquímicas , Prata , Glucose/química , Eletrodos
15.
Small ; 20(28): e2310212, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342699

RESUMO

The free-to-total prostate-specific antigen (f/t-PSA) ratio is of great significance in the accurate diagnosis of prostate cancer. Herein, a smartphone-based detection system is reported using a colorimetric reaction integrated with proximity-induced bio-barcode and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a assay for f/t-PSA ratio detection. DNA/antibody recognition probes are designed to bind f-PSA or t-PSA and induce the release of the DNA bio-barcode. The CRISPR/Cas12a system is activated by the DNA bio-barcode to release Ag+ from the C-Ag+-C structure of the hairpin DNA. The released Ag+ is used to affect the tetramethylbenzidine (TMB)-H2O2-based colorimetric reaction catalyzed by Pt nanoparticles (NPs), as the peroxidase-like activity of the Pt NPs can be efficiently inhibited by Ag+. A smartphone with a self-developed app is used as an image reader and analyzer to analyze the colorimetric reaction and provide the results. A limit of detection of 0.06 and 0.04 ng mL-1 is achieved for t-PSA and f-PSA, respectively. The smartphone-based method showed a linear response between 0.1 and 100 ng mL-1 of t-PSA or f-PSA. In tests with clinical samples, the smartphone-based method successfully diagnosed prostate cancer patients from benign prostatic hyperplasia patients and healthy cases with high sensitivity and specificity.


Assuntos
Sistemas CRISPR-Cas , Colorimetria , Nanopartículas Metálicas , Antígeno Prostático Específico , Smartphone , Colorimetria/métodos , Humanos , Masculino , Nanopartículas Metálicas/química , Neoplasias da Próstata/diagnóstico , Benzidinas/química , Prata/química , Peróxido de Hidrogênio/química , Platina/química , Técnicas Biossensoriais/métodos
16.
Comput Biol Med ; 171: 108187, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38402840

RESUMO

BACKGROUND: Emerging evidence suggests that aberrant alternative splicing (AS) may play an important role in tuberculosis (TB). However, current knowledge regarding the value of AS in TB progression and prognosis remains unclear. METHOD: Public RNA-seq datasets related to TB progression and prognosis were searched and AS analyses were conducted based on SUPPA2. Percent spliced in (PSI) was used for quantifying AS events and multiple machine learning (ML) methods were employed to construct predictive models. Area under curve (AUC), sensitivity and specificity were calculated to evaluate the model performance. RESULTS: A total of 1587 samples from 7 datasets were included. Among 923 TB-progression related differential AS events (DASEs), 3 events (GET1-skipping exon (SE), TPD52-alternative first exons (AF) and TIMM10-alternative 5' splice site (A5)) were selected as candidate biomarkers; however, their predictive performance was limited. For TB prognosis, 5 events (PHF23-AF, KIF1B-SE, MACROD2-alternative 3' splice site (A3), CD55-retained intron (RI) and GALNT11-AF) were selected as candidates from the 1282 DASEs. Six ML methods were used to integrate these 5 events and XGBoost outperformed than others. AUC, sensitivity and specificity of XGBoost model were 0.875, 81.1% and 83.5% in training set, while they were 0.805, 68.4% and 73.2% in test set. CONCLUSION: GET1-SE, TPD52-AF and TIMM10-A5 showed limited role in predicting TB progression, while PHF23-AF, KIF1B-SE, MACROD2-A3, CD55-RI and GALNT11-AF could well predict TB prognosis and work as candidate biomarkers. This work preliminarily explored the value of AS in predicting TB progression and prognosis and offered potential targets for further research.


Assuntos
Processamento Alternativo , Tuberculose , Humanos , Processamento Alternativo/genética , Sítios de Splice de RNA , Tuberculose/diagnóstico , Tuberculose/genética , RNA-Seq , Biomarcadores , Proteínas de Neoplasias , Proteínas de Homeodomínio
17.
ACS Nano ; 18(6): 5017-5028, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38305181

RESUMO

Herein, we propose a paper-based laboratory via enzyme-free nucleic acid amplification and nanomaterial-assisted cation exchange reactions (CERs) assisted single-cell-level analysis (PLACS). This method allowed for the rapid detection of mucin 1 and trace circulating tumor cells (CTCs) in the peripheral blood of lung cancer patients. Initially, an independently developed method requiring one centrifuge, two reagents (lymphocyte separation solution and erythrocyte lysate), and a three-step, 45 min sample pretreatment was employed. The core of the detection approach consisted of two competitive selective identifications: copper sulfide nanoparticles (CuS NPs) to C-Ag+-C and Ag+, and dual quantum dots (QDs) to Cu2+ and CuS NPs. To facilitate multimodal point-of-care testing (POCT), we integrated solution visualization, test strip length reading, and a self-developed hand-held fluorometer readout. These methods were detectable down to ag/mL of mucin 1 concentration and the single-cell level. Forty-seven clinical samples were assayed by fluorometer, yielding 94% (30/32) sensitivity and 100% (15/15) specificity with an area under the curve (AUC) of 0.945. Nine and 15 samples were retested by a test strip and hand-held fluorometer, respectively, with an AUC of 0.95. All test results were consistent with the clinical imaging and the folate receptor (FR)-PCR kit findings, supporting its potential in early diagnosis and postoperative monitoring.


Assuntos
Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Mucina-1/genética , Biópsia Líquida , Técnicas de Amplificação de Ácido Nucleico
18.
Adv Sci (Weinh) ; 11(11): e2305592, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38192178

RESUMO

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Leucócitos Mononucleares , Mycobacterium tuberculosis/fisiologia , Linfócitos T , Células Matadoras Naturais
19.
iScience ; 27(1): 108736, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38269101

RESUMO

Herein, a hierarchical NiTe@NiFe-LDH core-shell array on Ni foam (NiTe@NiFe-LDH/NF) demonstrates its effectiveness for oxygen evolution reaction (OER) in alkaline seawater electrolyte. This NiTe@NiFe-LDH/NF array showcases remarkably low overpotentials of 277 mV and 359 mV for achieving current densities of 100 and 500 mA cm-2, respectively. Also, it shows a low Tafel slope of 68.66 mV dec-1. Notably, the electrocatalyst maintains robust stability over continuous electrolysis for at least 50 h at 100 mA cm-2. The remarkable performance and hierarchical structure advantages of NiTe@NiFe-LDH/NF offer innovative insights for designing efficient seawater oxidation electrocatalysts.

20.
Adv Sci (Weinh) ; 11(13): e2306364, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286670

RESUMO

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.


Assuntos
Linfócitos Intraepiteliais , Neoplasias da Glândula Tireoide , Humanos , Camundongos , Animais , Receptores de Antígenos de Linfócitos T gama-delta/genética , Estudos Transversais , Imunoterapia , Neoplasias da Glândula Tireoide/terapia
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