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1.
JAMA ; 331(16): 1369-1378, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38568601

RESUMO

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.


Assuntos
Antivirais , Transtornos Relacionados ao Uso de Opioides , Encaminhamento e Consulta , Telemedicina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Antivirais/uso terapêutico , Adulto , Estudos Prospectivos , Resposta Viral Sustentada , Hepatite C/tratamento farmacológico , New York , Prestação Integrada de Cuidados de Saúde , Hepatite C Crônica/tratamento farmacológico , Tratamento de Substituição de Opiáceos/métodos
2.
Mol Immunol ; 168: 1-9, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367301

RESUMO

Dysfunctional mutations in SAMHD1 cause Aicardi-Goutières Syndrome, an autoinflammatory encephalopathy with elevated interferon-α levels in the cerebrospinal fluid. Whether loss of function mutations in SAMHD1 trigger the expression of other cytokines apart from type I interferons in Aicardi-Goutières Syndrome is largely unclear. This study aimed to explore whether SAMHD1 dysfunction regulated the expression of IL-34, a key cytokine controlling the development and maintenance of microglia, in SH-SY5Y neural cells. We found that downregulation of SAMHD1 in SH-SY5Y cells resulted in the upregulation of IL-34 expression. The protein and mRNA levels of NF-κB p65, the transactivating subunit of a transcription factor NF-κB, were also upregulated in SAMHD1-knockdown SH-SY5Y cells. It was further found SAMHD1 knockdown in SH-SY5Y cells induced an upregulation of IL-34 expression through the canonical NF-κB-dependent pathway in which NF-κB p65, IKKα/ß and the NF-κB inhibitor IκBα were phosphorylated. Moreover, knockdown of SAMHD1 in SH-SY5Y cells led to the translocation of NF-κB p65 into the nucleus and promoted NF-κB transcriptional activity. In conclusion, we found SAMHD1 dysfunction induced IL-34 expression via NF-κB p65 in neuronal SH-SY5Y cells. This finding could lay the foundation for exploring the role of IL-34-targeting microglia in the pathogenesis of Aicardi-Goutières Syndrome.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Malformações do Sistema Nervoso , Neuroblastoma , Humanos , NF-kappa B/metabolismo , Proteína 1 com Domínio SAM e Domínio HD , Neuroblastoma/genética , Inibidor de NF-kappaB alfa , Citocinas , Interleucinas
3.
Int J Biol Macromol ; 255: 127921, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944741

RESUMO

To reduce the white pollution, the eco-friendly biodegradable poly (butylene adipate-co-terephthalate) (PBAT)-based films had attracted increasing interests worldwide. However, the high-cost of the PBAT had limited the large-scale development and application. In this work, 10 wt% low-cost lignin was introduced into the PBAT to prepare composite films by melt blending and blow molding, and the POSS(epoxy)8 was selected as the compatibilizer to improve the compatibility of PBAT and lignin. The maximum tensile strength and the nominal strain at break subsequently increased by 48.2 % and 21.4 % respectively, while the water vapor permeability enhanced by 9.9 %. Furthermore, the UV aging resistance of PBAT/lignin films were significantly improved, with only 1 wt% POSS(epoxy)8 content. This work provides an efficient strategy to foster the end-user confidence in the low-cost and eco-friendly biodegradable polymer materials with efficient performance.


Assuntos
Lignina , Poliésteres , Resinas Epóxi , Adipatos
4.
J Headache Pain ; 24(1): 141, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37858040

RESUMO

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.


Assuntos
Ketamina , Estimulação Elétrica Nervosa Transcutânea , Animais , Camundongos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cálcio/metabolismo , Ketamina/metabolismo , Dor , Canal de Cátion TRPA1
5.
Chemosphere ; 345: 140444, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839745

RESUMO

Due to its large specific surface area and great hydrophobicity, microplastics can adsorb polycyclic aromatic hydrocarbons (PAHs), affecting the bioavailability and the toxicity of PAHs to plants. This study aimed to evaluate the effects of D550 and D250 (with diameters of 550 µm and 250 µm) microplastics on phenanthrene (PHE) removal from soil and PHE accumulation in maize (Zea mays L.). Moreover, the effects of microplastics on rhizosphere microbial community of maize grown in PHE-contaminated soil would also be determined. The results showed that D550 and D250 microplastics decreased the removal of PHE from soil by 6.5% and 2.7% and significantly reduced the accumulation of PHE in maize leaves by 64.9% and 88.5%. Interestingly, D550 microplastics promoted the growth of maize and enhanced the activities of soil protease and alkaline phosphatase, while D250 microplastics significantly inhibited the growth of maize and decreased the activities of soil invertase, alkaline phosphatase and catalase, in comparison with PHE treatment. In addition, microplastics changed the rhizosphere soil microbial community and reduced the relative abundance of PAHs degrading bacteria (Pseudomonas, Massilia, Proteobacteria), which might further inhibit the removal of PHE from soil. This study provided a new perspective for evaluating the role of microplastics on the bioavailability of PHE to plants and revealing the combined toxicity of microplastics and PHE to soil microcosm and plant growth.


Assuntos
Microbiota , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Zea mays , Microplásticos , Plásticos , Rizosfera , Fosfatase Alcalina , Disponibilidade Biológica , Biodegradação Ambiental , Fenantrenos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo , Microbiologia do Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
6.
Analyst ; 148(19): 4850-4856, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37622412

RESUMO

Synthetic cannabinoids (SCs) are a series of artificial chemical substances with pharmacological properties similar to those of natural cannabinoids and their abuse poses a great risk to social security and human health. However, the highly sensitive detection of low concentrations of SCs in human serum remains a great challenge. In this work, we developed a highly sensitive, rapid and highly selective method for the detection of SCs in human serum. Magnetic molecularly imprinted polymer (MIP) nanocomposites were prepared through self-polymerization of dopamine and template molecules on the surfaces of magnetic beads. 9H-Carbazole-9-hexanol (9CH) was used as a template molecule because of its long chain structure shared with six synthetic cannabinoids and its ability to provide specific recognition sites. With these magnetic MIP nanoparticles, six SCs could be rapidly and effectively extracted from human blood. The concentrations of six SCs could be accurately determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The limits of detection were in the range of 0.1-0.3 ng mL-1. The proposed method is characterized by high sensitivity and selectivity, and has great potential for application in the analysis of practical samples.


Assuntos
Canabinoides , Impressão Molecular , Humanos , Polímeros Molecularmente Impressos , Cromatografia Líquida de Alta Pressão/métodos , Fenômenos Magnéticos , Impressão Molecular/métodos
7.
Scand J Immunol ; 98(4): e13314, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37515439

RESUMO

Aicardi-Goutières syndrome (AGS) is a rare monogenic autoimmune disease that primarily affects the brains of children patients. Its main clinical features include encephalatrophy, basal ganglia calcification, leukoencephalopathy, lymphocytosis and increased interferon-α (IFN-α) levels in the patient's cerebrospinal fluid (CSF) and serum. AGS may be caused by mutations in any one of nine genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11 and RNU7-1) that result in accumulation of self-nucleic acids in the cytoplasm or aberrant sensing of self-nucleic acids. This triggers overproduction of type I interferons (IFNs) and subsequently causes AGS, the prototype of type I interferonopathies. This review describes the discovery history of AGS with various genotypes and provides the latest knowledge of clinical manifestations and causative genes of AGS. The relationship between AGS and type I interferonopathy and potential therapeutic methods for AGS are also discussed in this review.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Interferon Tipo I , Malformações do Sistema Nervoso , Criança , Humanos , Malformações do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/genética , Interferon-alfa/genética , Encéfalo , Interferon Tipo I/genética , Mutação
8.
Front Nutr ; 10: 1102722, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275645

RESUMO

Background: Obesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender. Materials and methods: This prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations. Results: During a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17-3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer. Conclusion: This study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

9.
Biomimetics (Basel) ; 8(2)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37366838

RESUMO

To improve the identification accuracy of the vibration states of hydraulic units, an improved artificial rabbits optimization algorithm (IARO) adopting an adaptive weight adjustment strategy is developed for optimizing the support vector machine (SVM) to obtain an identification model, and the vibration signals with different states are classified and identified. The variational mode decomposition (VMD) method is used to decompose the vibration signals, and the multi-dimensional time-domain feature vectors of the signals are extracted. The IARO algorithm is used to optimize the parameters of the SVM multi-classifier. The multi-dimensional time-domain feature vectors are input into the IARO-SVM model to realize the classification and identification of vibration signal states, and the results are compared with those of the ARO-SVM model, ASO-SVM model, PSO-SVM model and WOA-SVM model. The comparative results show that the average identification accuracy of the IARO-SVM model is higher at 97.78% than its competitors, which is 3.34% higher than the closest ARO-SVM model. Therefore, the IARO-SVM model has higher identification accuracy and better stability, and can accurately identify the vibration states of hydraulic units. The research can provide a theoretical basis for the vibration identification of hydraulic units.

10.
Talanta ; 264: 124779, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37311328

RESUMO

Escherichia coli (E. coli) is one of the most ubiquitous foodborne pathogens that can cause infections and threaten human health. Herein, a colorimetric method for sensitive detection of E. coli was established by using enzyme-nanozyme cascade reaction for signal amplification. Gold nanoparticles (AuNPs) are well-known nanozymes due to their high peroxidase-like activity. When the dense cetyltrimethylammonium bromide (CTAB) membrane on the surfaces of AuNPs kept the substrate away from AuNPs, the peroxidase activity of AuNPs was inhibited. However, the CTAB membrane could be disrupted by Ag+, resulting in enhanced peroxidase activity of AuNPs. When E. coli was present, the enzyme-nanozyme cascade reaction was initiated. The substrate p-aminophenyl ß-D-galactopyranoside (PAPG) was hydrolyzed to the reductive p-aminophenol (PAP) by beta-galactosidase (ß-gal) in E. coli, reducing Ag+ to Ag. Consequently, CTAB-AuNPs remained weak peroxidase activity and could not catalyze the H2O2-mediated oxidation of TMB. As the amount of E. coli increased, the absorbance of TMB decreased along with a color change from deep blue to pink. The absorbance intensity displayed a linear dependence on E. coli from 1.0 × 102 to 1.0 × 109 CFU mL-1. Therefore, the proposed method holds good prospects in foodborne pathogenic bacteria detection.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Ouro/química , Nanopartículas Metálicas/química , Escherichia coli , Cetrimônio , Peróxido de Hidrogênio , Colorimetria/métodos , Peroxidase/química
11.
Cancers (Basel) ; 15(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37046693

RESUMO

(1) Background: Acute oral mucositis is the most common side effect for nasopharyngeal carcinoma patients receiving radiotherapy. Improper or delayed intervention to severe AOM could degrade the quality of life or survival for NPC patients. An effective prediction method for severe AOM is needed for the individualized management of NPC patients in the era of personalized medicine. (2) Methods: A total of 242 biopsy-proven NPC patients were retrospectively recruited in this study. Radiomics features were extracted from contrast-enhanced CT (CECT), contrast-enhanced T1-weighted (cT1WI), and T2-weighted (T2WI) images in the primary tumor and tumor-related area. Dosiomics features were extracted from 2D or 3D dose-volume histograms (DVH). Multiple models were established with single and integrated data. The dataset was randomized into training and test sets at a ratio of 7:3 with 10-fold cross-validation. (3) Results: The best-performing model using Gaussian Naive Bayes (GNB) (mean validation AUC = 0.81 ± 0.10) was established with integrated radiomics and dosiomics data. The GNB radiomics and dosiomics models yielded mean validation AUC of 0.6 ± 0.20 and 0.69 ± 0.14, respectively. (4) Conclusions: Integrating radiomics and dosiomics data from the primary tumor area could generate the best-performing model for severe AOM prediction.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 297: 122721, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37054572

RESUMO

We developed a novel fabrication of flexible surface-enhanced Raman scattering (SERS) substrate to perform selective and sensitive determination of thiram residue in fruits and juices. Au nanostars (Au NSs) with multi-branching structure were self-assembled on aminated Polydimethylsiloxane (PDMS) slides by electrostatic interaction. By measuring the Thiram's characteristic peak intensity at 1371 cm-1, the SERS method could distinguish Thiram from other pesticide residues. A good linear relationship between the peak intensity at 1371 cm-1 and thiram's concentration was established at the range from 0.01 ppm to 100 ppm and the Limit of detection is 0.0048 ppm. We directly used this SERS substrate to detect Thiram in apple juice. By standard addition method, recoveries varied in the range of 97.05% to 106.00% and the RSD were from 3.26% to 9.35%. The SERS substrate exhibited a good sensitivity, stability and selectively for the detection of Thiram in food samples, which can be spread as a common method for the detection of pesticides in food samples.


Assuntos
Malus , Nanopartículas Metálicas , Praguicidas , Tiram/análise , Malus/química , Praguicidas/análise , Frutas/química , Dimetilpolisiloxanos , Análise Espectral Raman/métodos , Nanopartículas Metálicas/química , Ouro/química
13.
Neurochem Res ; 48(8): 2350-2359, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36947308

RESUMO

Sympathetic axonal sprouting into dorsal root ganglia is a major phenomenon implicated in neuropathic pain, and sympathetic ganglia blockage may relieve some intractable chronic pain in animal pain models and clinical conditions. These suggest that sympathetic ganglia participated in the maintenance of chronic pain. However, the molecular mechanism underlying sympathetic ganglia-mediated chronic pain is not clear. Here, we found that spared nerve injury treatment upregulated the expression of ADAMTS4 and AP-2α protein and mRNA in the noradrenergic neurons of sympathetic ganglia during neuropathic pain maintenance. Knockdown the ADAMTS4 or AP-2α by injecting specific retro scAAV-TH (Tyrosine Hydroxylase)-shRNA ameliorated the mechanical allodynia induced by spared nerve injury on day 21 and 28. Furthermore, chromatin immunoprecipitation and coimmunoprecipitation assays found that spared nerve injury increased the recruitment of AP-2α to the ADAMTS4 gene promoter, the interaction between AP-2α and histone acetyltransferase p300 and the histone H4 acetylation on day 28. Finally, knockdown the AP-2α reduced the acetylation of H4 on the promoter region of ADAMTS4 gene and suppressed the increase of ADAMTS4 expression induced by spared nerve injury. Together, these results suggested that the enhanced interaction between AP-2α and p300 mediated the epigenetic upregulation of ADAMTS4 in sympathetic ganglia noradrenergic neurons, which contributed to the maintenance of spared nerve injury induced neuropathic pain.


Assuntos
Dor Crônica , Neuralgia , Traumatismos do Sistema Nervoso , Ratos , Animais , Regulação para Cima , Dor Crônica/metabolismo , Ratos Sprague-Dawley , Neuralgia/genética , Neuralgia/metabolismo , Gânglios Simpáticos , Gânglios Espinais/metabolismo , Traumatismos do Sistema Nervoso/metabolismo , Epigênese Genética
14.
Anal Chim Acta ; 1249: 340937, 2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-36868772

RESUMO

Poly(ADP)ribose polymerase-1 (PARP-1) has attracted much attention as a tumor marker in recent years. Based on the large negative charge and hyperbranched structure of PARP-1 amplified products (PAR), many detection methods have been established. Herein, we proposed a label-free electrochemical impedance detection method based on the large amount of phosphate groups (PO43-) on the surface of PAR. Although EIS method has high sensitivity, it is not sensitive enough to discern PAR effectively. Therefore, biomineralization was incorporated to increase the resistance value (Rct) distinctly because of the poor electrical conductivity of CaP. During biomineralization process, plentiful Ca2+ was captured by PO43- of PAR through electrostatic interaction, resulting in an increasing Rct of modified ITO electrode. In contrast, when PRAP-1 was absent, only a little Ca2+ was adsorbed on the phosphate backbone of the activating dsDNA. As a result, the biomineralization effect was slight and only a negligible Rct change occurred. Experiment results showed that Rct was associated closely with the activity of PARP-1. There was a linear correlation between them when the activity value was in the range of 0.005-1.0 U. The calculated detection limit was 0.003 U. Results of real samples detection and the recovery experiments were satisfactory, indicating the method has an excellent application prospect.


Assuntos
Biomineralização , Espectroscopia Dielétrica , Inibidores de Poli(ADP-Ribose) Polimerases , Biomarcadores Tumorais , Fosfatos
15.
JCO Precis Oncol ; 7: e2200522, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36848612

RESUMO

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have a significant prognostic value in cancers. However, very few automated, deep learning-based TIL scoring algorithms have been developed for colorectal cancer (CRC). MATERIALS AND METHODS: We developed an automated, multiscale LinkNet workflow for quantifying TILs at the cellular level in CRC tumors using H&E-stained images from the Lizard data set with annotations of lymphocytes. The predictive performance of the automatic TIL scores (TILsLink) for disease progression and overall survival (OS) was evaluated using two international data sets, including 554 patients with CRC from The Cancer Genome Atlas (TCGA) and 1,130 patients with CRC from Molecular and Cellular Oncology (MCO). RESULTS: The LinkNet model provided outstanding precision (0.9508), recall (0.9185), and overall F1 score (0.9347). Clear continuous TIL-hazard relationships were observed between TILsLink and the risk of disease progression or death in both TCGA and MCO cohorts. Both univariate and multivariate Cox regression analyses for the TCGA data demonstrated that patients with high TIL abundance had a significant (approximately 75%) reduction in risk for disease progression. In both the MCO and TCGA cohorts, the TIL-high group was significantly associated with improved OS in univariate analysis (30% and 54% reduction in risk, respectively). The favorable effects of high TIL levels were consistently observed in different subgroups (classified according to known risk factors). CONCLUSION: The proposed deep-learning workflow for automatic TIL quantification on the basis of LinkNet can be a useful tool for CRC. TILsLink is likely an independent risk factor for disease progression and carries predictive information of disease progression beyond the current clinical risk factors and biomarkers. The prognostic significance of TILsLink for OS is also evident.


Assuntos
Neoplasias Colorretais , Linfócitos do Interstício Tumoral , Humanos , Prognóstico , Progressão da Doença , Neoplasias Colorretais/diagnóstico
16.
Chemosphere ; 316: 137807, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36634717

RESUMO

The widespread occurrence of bisphenol A (BPA), a typical endocrine-disrupting compound, poses potential threat to ecosystem and public health. Carotenoids are essential natural pigments, playing important roles in photosynthesis and antioxidant defense of plants. This study aimed to verify the value of carotenoids in enhancing plant tolerance to BPA stress and improving phytoremediation efficiency of tobacco (Nicotiana tabacum L.), through exogenous application of ß-carotene (a typical carotenoid) and endogenous upregulation of carotenoids by overexpression of ß-carotene hydroxylase (chyb) gene in tobacco. The results demonstrated that exogenous applied ß-carotene alleviated the toxic effects of BPA exposure (100 mg kg-1) on wild-type (WT) tobacco plants after being cultivated for 40 d, reflecting by the increase of biomass (201.2%), chlorophyll content (27.5%) and the decrease of malondialdehyde (MDA) content (70.7%). Similar with the results of exogenous application of ß-carotene, chyb gene overexpressing tobacco showed less phytotoxicity exposed to BPA, through enhancing photosynthetic efficiency (42.1%) and reducing reactive oxygen species (ROS) production (18%). Notably, about 94.8% BPA in contaminated soil was removed under the cultivation of transgenic tobacco for 40 d, however, only 82.7% was removed in that of WT tobacco. Moreover, transgenic tobacco is beneficial for the growth of plant roots, thus upregulating the abundance of bacteria contributing to BPA degradation or soil nutrient cycling (e.g., Proteobacteria, Acidobacteria, Actinobacteria, Sphingomonas and MND1), which might further help to enhance plant growth and improve BPA removal efficiency in soil. This study extended our understanding of the possible mechanisms of carotenoids-involved alleviation of BPA stress in tobacco, providing a novel strategy to improve phytoremediation efficiency of plants in BPA contaminated soil.


Assuntos
Carotenoides , Poluentes do Solo , Carotenoides/metabolismo , /metabolismo , beta Caroteno , Biodegradação Ambiental , Ecossistema , Fotossíntese/genética , Solo , Poluentes do Solo/metabolismo
17.
J Int Neuropsychol Soc ; 29(1): 1-11, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630994

RESUMO

OBJECTIVE: Emerging evidence suggests low vision may be a modifiable risk factor for cognitive decline. We examined effects of baseline visual acuity (VA) on level of, and change in, cognitive test performance over 9 years. METHOD: A population-based sample of 1,621 participants (average age 77 years) completed a comprehensive neuropsychological evaluation and VA testing at baseline and reassessed at nine subsequent annual visits. Linear regression modeled the association between baseline VA and concurrent cognitive test performance. Joint modeling of a longitudinal sub-model and a survival sub-model to adjust for attrition were used to examine associations between baseline VA and repeated cognitive test performance over time. RESULTS: Better baseline VA was associated cross-sectionally with younger age, male sex, greater than high school education, and higher baseline neuropsychological test scores on both vision-dependent (B coefficient range -0.163 to -0.375, p = .006 to <.001) and vision-independent tests (-0.187 to -0.215, p = .003 to .002). In longitudinal modeling, better baseline VA was associated with slower decline in vision-dependent tests (B coefficient range -0.092 to 0.111, p = .005 to <.001) and vision-independent tests (-0.107 to 0.067, p = .007 to <.001). CONCLUSIONS: Higher VA is associated with higher concurrent cognitive abilities and slower rates of decline over 9 years in both vision-dependent and vision-independent tests of memory, language, and executive functioning. Findings are consistent with emerging literature supporting vision impairment in aging as a potentially modifiable risk factor for cognitive decline. Clinicians should encourage patient utilization of vision assessment and correction with the added aim of protecting cognition.


Assuntos
Disfunção Cognitiva , Humanos , Masculino , Idoso , Estudos Longitudinais , Cognição , Envelhecimento , Testes Neuropsicológicos , Acuidade Visual
18.
IEEE Trans Pattern Anal Mach Intell ; 45(5): 5461-5480, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36040934

RESUMO

Blind image super-resolution (SR), aiming to super-resolve low-resolution images with unknown degradation, has attracted increasing attention due to its significance in promoting real-world applications. Many novel and effective solutions have been proposed recently, especially with powerful deep learning techniques. Despite years of efforts, it still remains as a challenging research problem. This paper serves as a systematic review on recent progress in blind image SR, and proposes a taxonomy to categorize existing methods into three different classes according to their ways of degradation modelling and the data used to solve the SR model. This taxonomy helps summarize and distinguish among existing methods. We hope to provide insights into current research states, as well as revealing novel research directions worth exploring. In addition, we make a summary on commonly used datasets and previous competitions related to blind image SR. Last but not least, a comparison among different methods is provided with detailed analysis on their merits and demerits using both synthetic and real testing images.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121830, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179567

RESUMO

Rapid, sensitive and simultaneous detection of multiple bacteria in foodborne is still a major challenge in public health field. Here, a fluorescence immunoassay that can achieve high-throughput detection of three Gram-positive foodborne pathogenic bacteria simultaneously was proposed. Vancomycin and bovine serum albumin conjugate (Van-BSA) was immobilized on a polycarbonate chip to capture three Gram-positive foodborne pathogenic bacteria, Staphylococcus aureus (S. aureus), Bacillus cereus (B. cereus) and Listeria monocytogenes (L. monocytogenes). CdSe/ZnS quantum dot modified antibodies (Ab-QD) were prepared by carbodiimide coupling chemistry. Due to the affinity reaction between antibodies and proteins on the bacterial surface, the simultaneous detection of multiple Gram-positive bacteria was achieved by monitoring the fluorescence signal of quantum dot by a portable microfluidic chip analyzer. Under optimal conditions, low detection limits was 18 CFU/well, 3 CFU/well and 36 CFU/well for S. aureus, B. cereus and L. monocytogenes, respectively. With satisfactory accuracy and precision, the proposed fluorescence immunoassay holds good prospects to detect pathogens in real food samples.


Assuntos
Listeria monocytogenes , Infecções Estafilocócicas , Humanos , Animais , Leite , Microbiologia de Alimentos , Staphylococcus aureus , Imunoensaio
20.
Oxid Med Cell Longev ; 2022: 6568748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36567858

RESUMO

Oxidative stress plays a key role in cerebral ischemia/reperfusion injury. Artemisinin (ART) has antioxidative stress activity in addition to its powerful antimalarial effects. In this article, we investigated the effect of ART on OGD/R-induced oxidative stress injury and its underlying mechanisms. We used oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model of cerebral ischemia/reperfusion (I/R) injury. CCK-8 and lactate dehydrogenase (LDH) release were used to assess cellular damage. Measurement of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and mitochondrial membrane potential (MMP) estimates oxidative stress-induced damage and protection from ART effect. OGD/R treatment aggravated oxidative stress damage, whereas ART reversed the effects of OGD/R. Autophagy is closely related to oxidative stress; in order to confirm whether the antioxidative stress effect of ART is related to PHB2-mediated autophagy, we examined the protein expression of prohibitin 2 (PHB2), TOMM20, p62, and the conversion of microtubule-associated protein light chain 3I (LC3I) to LC3II and found that the protein expression of PHB2, TOMM20, p62, and LC3II/LC3I was significantly correlated with OGD/R treatment. The colocalization of PHB2 and LC3, TOMM20, and LC3 was reduced after OGD/R treatment, and ART reversed this change. After silencing PHB2, the protective effect of ART against OGD/R-induced oxidative stress injury was reduced, the protein expressions of PHB2, TOMM20 and LC3II/LC3I and the colocalization of PHB2 and LC3, TOMM20, and LC3 were decreased. We used chloroquine to block the lysosomal pathway and found that ART increased the conversion of LC3I to LC3II, silencing PHB2 which inhibited the conversion of LC3I to LC3II, and impaired mitophagy. Our findings showed that ART attenuated OGD/R-induced oxidative stress damage through PHB2-mediated mitophagy. To the current knowledge, our study is the first to demonstrate that ART attenuates OGD/R-induced oxidative stress injury through PHB2-mediated autophagy in the human neuroblastoma SH-SY5Y cell line, which provided new insights into the treatment of OGD/R injury.


Assuntos
Artemisininas , Isquemia Encefálica , Neuroblastoma , Traumatismo por Reperfusão , Humanos , Apoptose , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Linhagem Celular , Autofagia , Estresse Oxidativo , Isquemia Encefálica/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Infarto Cerebral , Reperfusão , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Glucose/metabolismo
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