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1.
JAMA Oncol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949926

RESUMO

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

2.
Circ Res ; 135(2): 301-313, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38860363

RESUMO

BACKGROUND: The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with accessibility to its transcriptional promoter sites remains unresolved, especially in the setting of mature terminally differentiated (nonreplicative) cardiomyocytes. METHODS: Male and female control or TRIM35 (tripartite motif containing 35) overexpression adolescent (aged 1-3 months) and adult (aged 4-6 months) transgenic mice were used for all in vivo experiments. Primary adolescent or adult mouse cardiomyocytes were isolated from control or TRIM35 overexpression transgenic mice for all in vitro experiments. Adenovirus or small-interfering RNA was used for all molecular experiments to overexpress or knockdown, respectively, target genes in primary mouse cardiomyocytes. Patient dilated cardiomyopathy or nonfailing left ventricle samples were used for translational and mechanistic insight. Chromatin immunoprecipitation and DNA sequencing or quantitative real-time polymerase chain reaction (qPCR) was used to assess P53 binding to its transcriptional promoter targets, and RNA sequencing was used to identify disease-specific signaling pathways. RESULTS: Here, we show that E3-ubiquitin ligase TRIM35 can directly monoubiquitinate lysine-120 (K120) on histone 2B in postnatal mature cardiomyocytes. This epigenetic modification was sufficient to promote chromatin remodeling, accessibility of P53 to its transcriptional promoter targets, and elongation of its transcribed mRNA. We found that increased P53 transcriptional activity (in cardiomyocyte-specific Trim35 overexpression transgenic mice) was sufficient to initiate heart failure and these molecular findings were recapitulated in nonischemic human LV dilated cardiomyopathy samples. CONCLUSIONS: These findings suggest that TRIM35 and the K120Ub-histone 2B epigenetic modification are molecular features of cardiomyocytes that can collectively predict dilated cardiomyopathy pathogenesis.


Assuntos
Insuficiência Cardíaca , Histonas , Camundongos Transgênicos , Miócitos Cardíacos , Proteína Supressora de Tumor p53 , Ubiquitinação , Animais , Miócitos Cardíacos/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Masculino , Camundongos , Feminino , Histonas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Células Cultivadas , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Regiões Promotoras Genéticas , Camundongos Endogâmicos C57BL
3.
Bioorg Med Chem Lett ; 106: 129735, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38588785

RESUMO

A series of 1,4-benzoxazin-3-one analogs were investigated to discover mode-selective TRPV1 antagonists, since such antagonists are predicted to minimize target-based adverse effects. Using the high-affinity antagonist 2 as the lead structure, the structure activity relationship was studied by modifying the A-region through incorporation of a polar side chain on the benzoxazine and then by changing the C-region with a variety of substituted pyridine, pyrazole and thiazole moieties. The t-butyl pyrazole and thiazole C-region analogs provided high potency as well as mode-selectivity. Among them, antagonist 36 displayed potent and capsaicin-selective antagonism with IC50 = 2.31 nM for blocking capsaicin activation and only 47.5 % inhibition at 3 µM concentration toward proton activation, indicating that more than a 1000-fold higher concentration of 36 was required to inhibit proton activation than was required to inhibit capsaicin activation. The molecular modeling study of 36 with our homology model indicated that two π-π interactions with the Tyr511 and Phe591 residues by the A- and C-region and hydrogen bonding with the Thr550 residue by the B-region were critical for maintaining balanced and stable binding. Systemic optimization of antagonist 2, which has high-affinity but full antagonism for activators of all modes, led to the mode-selective antagonist 36 which represents a promising step in the development of clinical TRPV1 antagonists minimizing side effects such as hyperthermia and impaired heat sensation.


Assuntos
Benzoxazinas , Canais de Cátion TRPV , Ureia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Relação Estrutura-Atividade , Benzoxazinas/química , Benzoxazinas/farmacologia , Benzoxazinas/síntese química , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia , Ureia/síntese química , Humanos , Estrutura Molecular , Animais , Capsaicina/farmacologia , Capsaicina/química , Descoberta de Drogas , Relação Dose-Resposta a Droga
4.
J Colloid Interface Sci ; 661: 761-771, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38325174

RESUMO

Tetracycline (TC) antibiotics, extensively utilized in livestock farming and aquaculture, pose significant environmental challenges. Photocatalysis, leveraging renewable sunlight and reusable photocatalysts, offers a promising avenue for mitigating TC pollution. However, identifying robust photocatalysts remains a formidable challenge. This study introduces a novel hollow-flower-ball-like nanoheterojunction composed of a nitrogen-rich covalent organic framework (N-COF) coupled with BiOBr (BOB), a semiconductor with a higher Fermi level. The synthesized N-COF/BOB S-scheme nanoheterojunction features an expanded contact interface, strengthened chemical bonding, and unique band topologies. The N-COF/BOB composites showcased exceptional TC degradation performance, achieving an 81.2% removal of 60 mg/L TC within 2 h, markedly surpassing the individual efficiencies of N-COF and BOB by factors of 3.80 and 5.96, respectively. Furthermore, the total organic carbon (TOC) removal efficiency highlights a superior mineralization capacity in the N-COF/BOB composite compared to the individual components, N-COF and BOB. The toxicity assessment revealed that the degradation intermediates possess diminished environmental toxicity. This enhanced performance is ascribed to the robust S-scheme nanoheterojunction structure, which promotes efficient photoinduced electron transfer from BOB to N-COF. This process also augments the separation of photogenerated charge carriers, resulting in an increased yield of superoxide radicals (∙O2-) and hydroxyl radicals (∙OH). These reactive species significantly contribute to the degradation and mineralization of TC. Consequently, this study introduces a sustainable approach for addressing emerging antibiotic contaminants, employing COF-based photocatalysts.


Assuntos
Antibacterianos , Bismuto , Radical Hidroxila , Transporte de Elétrons , Tetraciclinas , Tetraciclina
5.
Bioorg Med Chem Lett ; 101: 129656, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38355061

RESUMO

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity. Among them, 51 and 54 displayed potent and capsaicin-selective antagonism with IC50 = 2.85 and 3.27 nM to capsaicin activation and 28.5 and 31.5 % inhibition at 3 µM concentration toward proton activation, respectively. The molecular modeling study of 51 with our homology model indicated that the hydroxyethyl side chain in the A-region interacted with Arg557 and Glu570, the urea B-region engaged in hydrogen bonding with Tyr511 and Thr550, respectively, and the pyrazole C-region made two hydrophobic interactions with the receptor. Optimization of antagonist 2, which has full antagonism for activators of all modes, lead to mode-selective antagonists 51 and 54. These observations will provide insight into the future development of clinical TRPV1 antagonists without target-based side effects.


Assuntos
Capsaicina , Ureia , Ureia/química , Capsaicina/farmacologia , Relação Estrutura-Atividade , Modelos Moleculares , Pirazóis/farmacologia , Canais de Cátion TRPV
6.
Clin Genitourin Cancer ; 22(1): 23-32, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37574436

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , MicroRNAs/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
7.
Cancer ; 129(18): 2864-2870, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37424308

RESUMO

BACKGROUND: Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought. METHODS: An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals. RESULTS: Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50-70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25-65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2-4.2; p < .01) than non-Indigenous men. CONCLUSIONS: Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Detecção Precoce de Câncer , Assistência de Saúde Universal , Canadá/epidemiologia
8.
Bioorg Med Chem Lett ; 91: 129353, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37271378

RESUMO

The natural products neorautenol and shinpterocarpin and their structural analogs were investigated as novel anticancer agents. Twenty-four analogs, including analogs containing a polar chain and simplified analogs, were synthesized efficiently by a modified method from previous reports. The antitumor screening of synthesized compounds toward six cancer cell lines indicated that compounds 37, 42 and 43 with a dialkylaminoethyl-type side chain exhibited more promising activity than neorautenol and shinpterocarpin against lung and colon cancer lines with a range of 4-9 µM. They showed selective toxicity in normal cells.


Assuntos
Antineoplásicos , Estrutura Molecular , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral
9.
J Colloid Interface Sci ; 643: 102-114, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37054545

RESUMO

Covalent organic frameworks (COFs) are crystalline porous materials with enormous potential for realizing solar-driven CO2-to-fuel conversion, yet the sluggish transfer/separation of photoinduced electrons and holes remains a compelling challenge. Herein, a step (S)-scheme heterojunction photocatalyst (CuWO4-COF) was rationally fabricated by a thermal annealing method for boosting CO2 conversion to CO. The optimal CuWO4/COF composite sample, integrating 10 wt% CuWO4 with an olefin (C═C) linked COF (TTCOF), achieved a remarkable gas-solid phase CO yield as high as 7.17 ± 0.35 µmol g-1h-1 under visible light irradiation, which was significantly higher than the pure COF (1.6 ± 0.29 µmol g-1h-1). The enhanced CO2 conversion rate could be attributable to the interface engineering effect and the formation of internal electric field (IEF) directing from TTCOF to CuWO4 according to the theoretical calculation and experimental results, which also proves the electrons transfer from TTCOF to CuWO4 upon hybridization. In addition, driven by the IEF, the photoinduced electrons can be steered from CuWO4 to TTCOF under visible light irradiation as well-elucidated by in-situ irradiated X-ray photoelectron spectroscopy, verifying the S-scheme charge transfer pathway over CuWO4/COF composite heterojunctions, which greatly foster the photoreduction activity of CO2. The preparation technique of the S-scheme heterojunction photocatalyst in this study provides a paradigmatic protocol for photocatalytic solar fuel generation.

10.
Small ; 19(7): e2206407, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36464629

RESUMO

Seeking highly-efficient, non-pollutant, and chemically robust photocatalysts for visible-light-driven ammonia production still remained challenging, especially in pure water. The key bottle-necks closely correlate to the nitrogen activation, water oxidization, and hydrogen evolution reaction (HER) processes. In this study, a novel Bi decorated imine-linked COF-TaTp (Bi/COF-TaTp) through N-Bi-O coordination is reasonably designed to achieve a boosting solar-to-ammonia conversion of 61 µmol-1  g-1  h-1 in the sacrificial-free system. On basis of serial characterizations and DFT calculations, the incorporated Bi is conducive to the acceleration of charge carriers transfer and N2 activation through the donation and back-donation mode. The N2 adsorption energy of 5% Bi/COF-TaTp is calculated to be -0.19 eV in comparison with -0.09 eV of the pure COF-TaTp and the electron exchange between N2 and the modified catalyst is much more intensive. Moreover, the accompanied hydrogen production process is effectively inhibited by Bi modification, demonstrated by the higher energy barrier for HER over Bi/COF-TaTp (2.62 eV) than the pure COF-TaTp (2.31 eV) when using H binding free energy (ΔGH* ) as a descriptor. This work supplies novel insights for the design of photocatalysts for N2 reduction and intensifies the understanding of N2 adsorption and activation over covalent organic frameworks-based materials.

11.
Environ Res ; 216(Pt 1): 114541, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228690

RESUMO

Semiconductor-based solar-driven CO2 to fuels has been widely reckoned as an ingenious approach to tackle energy crisis and climate change simultaneously. However, the high carrier recombination rate of the photocatalyst severely dampens their photocatalytic uses. Herein, an inorganic-organic heterojunction was constructed by in-situ growing a dioxin-linked covalent organic framework (COF) on the surface of rod-shaped ß-Ga2O3 for solar-driven CO2 to fuel. This novel heterojunction is featured with an ultra-narrow bandgap COF-318 (absorption edge = 760 nm), which is beneficial for fully utilizing the visible light spectrum, and a wide bandgap ß-Ga2O3 (absorption edge = 280 nm) to directional conduct electrons from COF to reduce CO2 without electron-hole recombination occurred. Results showed that the solar to fuels performance over ß-Ga2O3/COF was much superb than that of COF. The optimized Ga2O3/COF achieved an outstanding CO evolution rate of 85.8 µmol h-1·g-1 without the need of any sacrificial agent or cocatalyst, which was 15.6 times more efficient than COF. Moreover, the analyses of photoluminescence electrochemical characterizations and density functional theory (DFT) calculations revealed that the fascinate construction of ß-Ga2O3/COF heterojunction significantly favored charge separation and the directional transfer of photogenerated electrons from COF to ß-Ga2O3 followed by CO2. This study paves the way for developing effective COF-based semiconductor photocatalysts for solar-to-fuel conversion.


Assuntos
Estruturas Metalorgânicas , Catálise , Dióxido de Carbono , Fotossíntese , Semicondutores
12.
Nanomaterials (Basel) ; 12(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36500734

RESUMO

Photocatalysis offers a sustainable approach for recalcitrant organic pollutants degradation, yet it is still challenging to seek robust photocatalysts for application purposes. Herein, a novel NiFe layered double hydroxide (LDH)/covalent triazine framework (CTF-1) Z-scheme heterojunction photocatalyst was rationally designed for antibiotics degradation under visible light irradiation. The NiFe-LDH/CTF-1 nanocomposites were readily obtained via in situ loading of NiFe-LDH on CTF-1 through covalent linking. The abundant coupling interfaces between two semiconductor counterparts lay the foundation for the formation of Z-scheme heterostructure, thereby effectively promoting the transfer of photogenerated electrons, inhibiting the recombination of carriers, as well as conferring the nanocomposites with stronger redox ability. Consequently, the optimal photocatalytic activity of the LDH/CTF heterojunction was significantly boosted for the degradation of a typical antibiotic, tetracycline (TC). Additionally, the photodegradation process and the mineralization of TC were further elucidated. These results envision that the LDH/CTF-1 can be a viable photocatalyst for long-term and sustainable wastewater treatment.

13.
Small ; 18(52): e2205388, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36344463

RESUMO

Exploiting cost-effective, high-efficiency, and contamination-free semiconductors for photocatalytic nitrogen reduction reaction (N2 RR) is still a great challenge, especially in sacrificial-free system. On basis of the electron "acceptance-donation" concept, a boron-doped and carbon-deficient g-C3 N4 (Bx CvN) is herein developed through precise dopant and defect engineering. The optimized B15 CvN exhibisted an NH3 production rate of 135.3 µmol h-1  g-1 in pure water with nine-fold enhancement to the pristine graphitic carbon nitride (g-C3 N4 ), on account of the markedly elevated visible-light harvesting, N2 activation, and multi-directional photoinduced carriers transfer. The decorated B atoms with coexistent occupied and empty sp3 hybridized orbitals are theoretically proved to be in charge of the increase of N2 adsorption energy from -0.08 to -0.26 eV and the change in N2 adsorption model from one-way to two-way end-on pattern. Noticeably, the elaborate coordination of doped B atoms and carbon vacancies greatly facilitated the interlayer interaction and vertical charge migration of Bx CvN, which is distinctly revealed through the charge density difference calculations. The current study provides an alternative groundbreaking perspective for advancing photocatalytic N2 RR through the targeted configuration of the defect and dopant sites.

14.
Future Oncol ; 18(29): 3311-3322, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36047424

RESUMO

Background: Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. Materials & methods: A total of 224 participants were involved in this three-cohort trial. A total of 15 candidate miRNAs were selected, and miRNAs with diagnostic ability were screened out with quantitative reverse transcription PCR. Diagnostic capability was ascertained by the receiver operating characteristic curve and area under the curve. Bioinformatics analysis was constructed for target gene prediction and functional annotation. Results: Six candidate miRNAs showed significantly different expression between bladder cancer patients and normal controls, and the final diagnostic panel comprised miR-181b-5p, miR-183-5p, miR-199-5p and miR-221-3p. Conclusion: This four-miRNA panel could represent a stable biomarker for bladder cancer diagnosis.


Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. After an experiment composed of 224 participants, the authors screened out six candidate miRNAs that may contribute to diagnosing bladder cancer. The authors also repeatedly verified the reliability of candidate miRNAs. Finally, a combination of multiple miRNAs, consisting of miR-181b-5p, miR-183-5p, miR-199-5p, and miR-221-3p, was better and more reliable in predicting bladder cancer occurrence.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Curva ROC , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética
15.
Front Genet ; 13: 897827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938021

RESUMO

Background: Renal cell carcinoma (RCC) has been a major health problem and is one of the most malignant tumors around the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The aim of this study was to explore serum miRNAs as potential biomarkers for screening RCC. Methods: A three-phase study was conducted to explore serum miRNAs as potential biomarkers for screening RCC. In the screening phase, 12 candidate miRNAs related to RCC were selected for further study by the ENCORI database with 517 RCC patients and 71 NCs. A total of 220 participants [108 RCC patients and 112 normal controls (NCs)] were enrolled for training and validation. The dysregulated candidate miRNAs were further confirmed with 30 RCC patients and 30 NCs in the training phase and with 78 RCC patients and 82 NCs in the validation phase. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used for assessing the diagnostic value of miRNAs. Bioinformatic analysis and survival analysis were also included in our study. Results: Compared to NCs, six miRNAs (miR-18a-5p, miR-138-5p, miR-141-3p, miR-181b-5p, miR-200a-3p, and miR-363-3p) in serum were significantly dysregulated in RCC patients. A four-miRNA panel was built by combining these candidate miRNAs to improve the diagnostic value with AUC = 0.908. ABCG1 and RNASET2, considered potential target genes of the four-miRNA panel, may play a significant role in the development of RCC. Conclusion: A four-miRNA panel in serum was identified for RCC screening in our study. The four--miRNA panel has a great potential to be a non-invasive biomarker for RCC screening.

16.
Am J Transl Res ; 14(7): 4606-4616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958461

RESUMO

BACKGROUND: Urinary bladder cancer (BCa) is globally the 10th most frequent cancer. As a novel diagnostic tool, miRNA in serum screening is non-invasive. This project aimed to determine particular serum miRNAs as novel biomarkers for diagnosing urinary BCa. METHODS: We designed a three-phase study with 122 healthy controls (HCs) and 132 BCa patients. The 30 miRNAs' expressions in serum from HCs and BCa patients were detected during the screening phase. The miRNAs with the most dysregulation were tested in the training (HCs vs. BCa, 30 each) and validation (80 HCs vs. 82 BCa) phase further. The diagnostic ability of these candidate miRNAs was estimated by the receiver operating characteristic (ROC) curves as well as the area under the ROC curve (AUC). The miRNAs' target genes and their annotations to functions were predicted utilizing bioinformatic assays. RESULTS: Six serum miRNAs (miR-124-3p, miR-182-5p, miR-1-3p, miR-196a-5p, miR-23b-3p and miR-34a-5p) had significantly different expression between BCa patients and HCs in the training and validation phase. The four-microRNA panel improved the diagnostic value, with AUC =0.985. The result of bioinformatic analysis showed that these miRNAs' target genes in the panel may be related to the MAPK signaling pathway in bladder cancer. CONCLUSIONS: Our study identified a four-miRNA panel that is a non-invasive new biomarker for diagnosing BCa.

17.
Water Res ; 222: 118901, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35933814

RESUMO

In the face of the growing global water crisis, membrane technology is a promising means of purifying water and wastewater. Silver nanoparticles (AgNPs) have been widely used to improve membrane performance, for antibiofouling, and to aid in photocatalytic degradation, thermal response, and electro-conductivity. However, several critical issues such as short antimicrobial periods, trade-off effects and silver inactivation seriously restrict the engineering application of AgNPs-incorporated membranes. In addition, there is controversy around the use of AgNPs given the toxic preparation process and environmental/biological risks. Hence, it is of great significance to summarize and analyze the recent developments and critical challenges in the use of AgNPs-incorporated membranes in water and wastewater treatment, and to propose potential solutions. We reviewed the different properties and functions of AgNPs and their corresponding applications in AgNPs-incorporated membranes. Recently, multifunctional, novel AgNP-incorporated membranes combined with other functional materials have been developed with high-performance. We further clarified the synergistic mechanisms between AgNPs and these novel nanomaterials and/or polymers, and elucidated their functions and roles in membrane separation. Finally, the critical challenges of AgNPs-incorporated membranes and the proposed solutions were outlined: i) Prolonging the antimicrobial cycle through long-term and controlled AgNPs release; ii) Overcoming the trade-off effect and organic fouling of the AgNPs-incorporated membranes; iii) Preparation of sustainable AgNPs-incorporated membranes; iv) Addressing biotoxicity induced by AgNPs; and v) Deactivation of AgNPs-incorporated membrane. Overall, this review provides a comprehensive discussion of the advancements and challenges of AgNPs-incorporated membranes and guides the development of more robust, multi-functional and sustainable AgNPs-incorporated membranes.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Polímeros , Prata/farmacologia , Água
18.
J Colloid Interface Sci ; 628(Pt B): 573-582, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36007422

RESUMO

Photocatalysis offers a sustainable paradigm for solar-to-fuel conversion because it conflates the merits of renewable solar energy and reusable catalysts. However, the seek for robust photocatalysts that can utilize the full visible light spectrum remains challenging. Herein, cobalt quantum dots (Co QDs) were integrated into ultra-narrow bandgap dioxin linked covalent organic frameworks (COF-318) for photocatalytic solar-to-fuel conversion under full spectrum of visible light irradiation. The optimal Co10-COF exhibited superior photocatalytic CO2 reduction performance, affording a CO yield of 4232 µmol∙g-1∙h-1 and H2 evolution of 6611 µmol∙g-1∙h-1. Specifically, Co QDs played a crucial role in boosting the photocatalytic performance, which acted as electron collectors to capture the photoinduced electrons and then conveyed them to CO2 molecules. Moreover, the Co QDs modification significantly improved the CO2 adsorption and activation capacity, as well as prolonging the lifetime of photogenerated carriers. This work reveals an operable pathway for fabricating promising photocatalyst for visible-light-driven solar-to-fuel generation and provides insight into the impact of the integration of Co QDs on COF-based photocatalysts.

19.
ChemSusChem ; 15(18): e202201107, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35841604

RESUMO

It is of pivotal significance to explore robust photocatalysts to promote the photoreduction of CO2 into solar fuels. Herein, an intelligent metal-insulator-semiconductor (MIS) nano-architectural photosystem was constructed by electrostatic self-assembly between cetyltrimethylammonium bromide (CTAB) insulator-capped metal Ni nanoparticles (NPs) and covalent triazine-based frameworks (CTF-1). The metal-insulator-CTF composites unveiled a substantially higher CO evolution rate (1254.15 µmol g-1 h-1 ) compared with primitive CTF-1 (1.08 µmol g-1 h-1 ) and reached considerable selectivity (98.9 %) under visible-light irradiation. The superior photocatalytic CO2 conversion activity over Ni-CTAB-CTF nanoarchitecture could be attributed to the larger surface area, reinforced visible-light response, and CO2 capture capacity. More importantly, the Ni-CTAB-CTF nanoarchitecture endowed the photoexcited electrons on CTF-1 with the ability to tunnel across the thin CTAB insulating layer, directionally migrating to Ni NPs and thereby leading to the efficient separation of photogenerated electrons and holes in the photosystem. In addition, isotope-labeled (13 CO2 ) tracer results verified that the reduction products come from CO2 rather than the decomposition of the photocatalysts. This study opens a new avenue for establishing a highly efficient and selective artificial photosystem for CO2 conversion.


Assuntos
Dióxido de Carbono , Nanopartículas Metálicas , Cetrimônio , Metais , Semicondutores , Triazinas
20.
J Environ Qual ; 51(5): 837-871, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35899915

RESUMO

Despite the advancements in analytical techniques, there are still great challenges and difficulties in accurately and effectively quantifying and characterizing dissolved organic carbon (DOC) in environmental samples. The objectives of this review paper are (a) to understand the roles and variability of DOC along the water continuum; (b) to identify the constraints, inconsistences, limitations, and artifacts in DOC characterization; and (c) to provide recommendations and remarks to improve the analytical accuracy. For the first objective, we summarize the four ecological and engineering roles of DOC along the water continuum from source water to municipal utility, including nutrients and energy sources, controlling the fates of micropollutants, buffering capacity, and treatability and precursors of disinfection byproducts. We also discuss three major challenges in DOC analysis, including spatial and temporal variations, degradability and stability, and unknown structures and formulas. For the second objective, we review the procedures and steps in DOC analysis, including sampling in diverse environmental matrices, isolation of DOC fraction, storage and preservation techniques, and analyses on bulk chemical characteristics. We list and discuss the available options and evaluate the advantages and disadvantages of each choice. Last, we provide recommendations and remarks for each stage: sampling, isolation, storage, and analysis.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Carbono/análise , Matéria Orgânica Dissolvida , Água/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos
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