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1.
Asian J Androl ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624201

RESUMO

Knowledge about the effect of different prostate biopsy approaches on the prostate cancer detection rate (CDR) in patients with gray-zone prostate-specific antigen (PSA) is limited. We performed this study to compare the CDR among patients who underwent different biopsy approaches and had rising PSA levels in the gray zone. Two hundred and twenty-two patients who underwent transrectal prostate biopsy (TRB) and 216 patients who underwent transperineal prostate biopsy (TPB) between June 2016 and September 2022 were reviewed in this study. In addition, 110 patients who received additional targeted biopsies following the systematic TPB were identified. Clinical parameters, including age, PSA derivative, prostate volume (PV), and needle core count, were recorded. The data were fitted via propensity score matching (PSM), adjusting for potential confounders. TPB outperformed TRB in terms of the CDR (49.6% vs 28.3%, P = 0.001). The clinically significant prostate cancer (csPCa) detection rate was not significantly different between TPB and TRB (78.6% vs 68.8%, P = 0.306). In stratified analysis, TPB outperformed TRB in CDR when the age of patients was 65-75 years (59.0% vs 22.0%, P < 0.001), when PV was 25.00-50.00 ml (63.2% vs 28.3%, P < 0.001), and when needle core count was no more than 12 (58.5% vs 31.5%, P = 0.005). The CDR (P = 0.712) and detection rate of csPCa (P = 0.993) did not significantly differ among the systematic, targeted, and combined biopsies. TPB outperformed TRB in CDR for patients with gray-zone PSA. Moreover, performing target biopsy after systematic TPB provided no additional benefits in CDR.

2.
Sci Rep ; 14(1): 8136, 2024 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584172

RESUMO

Computational approaches for predicting the pathogenicity of genetic variants have advanced in recent years. These methods enable researchers to determine the possible clinical impact of rare and novel variants. Historically these prediction methods used hand-crafted features based on structural, evolutionary, or physiochemical properties of the variant. In this study we propose a novel framework that leverages the power of pre-trained protein language models to predict variant pathogenicity. We show that our approach VariPred (Variant impact Predictor) outperforms current state-of-the-art methods by using an end-to-end model that only requires the protein sequence as input. Using one of the best-performing protein language models (ESM-1b), we establish a robust classifier that requires no calculation of structural features or multiple sequence alignments. We compare the performance of VariPred with other representative models including 3Cnet, Polyphen-2, REVEL, MetaLR, FATHMM and ESM variant. VariPred performs as well as, or in most cases better than these other predictors using six variant impact prediction benchmarks despite requiring only sequence data and no pre-processing of the data.


Assuntos
Mutação de Sentido Incorreto , Proteínas , Virulência , Proteínas/genética , Sequência de Aminoácidos , Biologia Computacional/métodos
3.
World J Urol ; 42(1): 171, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506974

RESUMO

PURPOSE: This study aimed to explore the clinical characteristics of apalutamide-associated skin rash and management of skin rash in real-world Chinese patients with prostate cancer. METHODS: We investigated 138 patients with prostate cancer who received apalutamide in the Second Hospital of Tianjin Medical University from January 2022 to March 2023. The primary end points were the incidence of skin rash and the time to skin rash. The second end points were the grade of skin rash, the time to remission, the rate of recurrence of skin rash, clinical risk factors and management of skin rash. RESULTS: One hundred patients were analyzed. Patients were a median of 73 years old (IQR 68-77.75). Thirty-two patients (32%) developed apalutamide­associated skin rash. The median time to incidence and remission of skin rash were 57.5 and 11.5 days, respectively. Of 32 skin rash, 27 patients had apalutamide therapy maintained after rash remission. There were seven patients having recurrence of skin rash. By multivariable logistic regression analysis, we revealed that hypertension history (OR 3.22, 95% CI 1.09-9.53, p = 0.035), bad life-styles (OR 3.29, 95% CI 1.11-9.8, p = 0.032), ECOG ≥ 1 (OR 3.92, 95% CI 1.33-11.55, p = 0.013), and high tumor burden (OR 3.13, 95% CI 1.07-9.14, p = 0.037) were independently associated with higher incidence of skin rash. CONCLUSION: Nearly one-third of Chinese patients experienced skin rash after taking apalutamide in our study. The poor health patients might have a higher incidence of apalutamide-associated skin rash.


Assuntos
Exantema , Neoplasias de Próstata Resistentes à Castração , Tioidantoínas , Masculino , Humanos , Idoso , Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Exantema/induzido quimicamente , Exantema/epidemiologia , Exantema/tratamento farmacológico , China/epidemiologia , Antagonistas de Androgênios/uso terapêutico
4.
Front Plant Sci ; 15: 1358965, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38439983

RESUMO

Secondary salinization is a crucial constraint on agricultural progress in arid regions. The specific mulching irrigation technique not only exacerbates secondary salinization but also complicates field-scale soil salinity monitoring. UAV hyperspectral remote sensing offers a monitoring method that is high-precision, high-efficiency, and short-cycle. In this study, UAV hyperspectral images were used to derive one-dimensional, textural, and three-dimensional feature variables using Competitive adaptive reweighted sampling (CARS), Gray-Level Co-occurrence Matrix (GLCM), Boruta Feature Selection (Boruta), and Brightness-Color-Index (BCI) with Fractional-order differentiation (FOD) processing. Additionally, three modeling strategies were developed (Strategy 1 involves constructing the model solely with the 20 single-band variable inputs screened by the CARS algorithm. In Strategy 2, 25 texture features augment Strategy 1, resulting in 45 feature variables for model construction. Strategy 3, building upon Strategy 2, incorporates six triple-band indices, totaling 51 variables used in the model's construction) and integrated with the Seagull Optimization Algorithm for Random Forest (SOA-RF) models to predict soil electrical conductivity (EC) and delineate spatial distribution. The results demonstrated that fractional order differentiation highlights spectral features in noisy spectra, and different orders of differentiation reveal different hidden information. The correlation between soil EC and spectra varies with the order. 1.9th order differentiation is proved to be the best order for constructing one-dimensional indices; although the addition of texture features slightly improves the accuracy of the model, the integration of the three-waveband indices significantly improves the accuracy of the estimation, with an R2 of 0.9476. In contrast to the conventional RF model, the SOA-RF algorithm optimizes its parameters thereby significantly improving the accuracy and model stability. The optimal soil salinity prediction model proposed in this study can accurately, non-invasively and rapidly identify excessive salt accumulation in drip irrigation under membrane. It is of great significance to improve the growing conditions of cotton, increase the cotton yield, and promote the sustainable development of Xinjiang's agricultural economy, and also provides a reference for the prevention and control of regional soil salinization.

5.
Prostate ; 84(4): 376-388, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38116741

RESUMO

PURPOSE: The study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) three lesions cohort. METHODS: This study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor. Univariable and multivariable logistic regression analysis was conducted to ascertain hidden risk factors and constructed nomograms in PI-RADS three lesions cohort. RESULTS: In the whole cohort, the area under the ROC curve (AUC) of PHI is relatively high, which is 0.779. As radiographic parameters, the AUC of PI-RADS and ADC values was 0.702 and 0.756, respectively. The utilization of PHI and ADC values either individually or in combination significantly improved the diagnostic accuracy of the basic model. In PI-RADS three lesions cohort, the AUC for PCa was 0.817 in the training cohort and 0.904 in the validation cohort. The AUC for CSPCa was 0.856 in the training cohort and 0.871 in the validation cohort. When applying the nomogram for predicting PCa, 50.0% of biopsies could be saved, supplemented by 6.9% of CSPCa being missed. CONCLUSION: PHI and ADC values can be used as predictors of CSPCa. The nomogram included PHI, ADC values and other clinical predictors demonstrated an enhanced capability in detecting PCa and CSPCa within PI-RADS three lesions cohort.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Imageamento por Ressonância Magnética , Neoplasias da Próstata/patologia , Antígeno Prostático Específico/análise , Estudos Retrospectivos , Biópsia
6.
Anal Chem ; 95(50): 18487-18496, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38057291

RESUMO

In situ analysis of biomarkers in the tumor microenvironment (TME) is important to reveal their potential roles in tumor progression and early diagnosis of tumors but remains a challenge. In this work, a bottom-up modular assembly strategy was proposed for a multifunctional protein-nucleic chimeric probe (PNCP) for in situ mapping of cancer-specific proteases. PNCP, containing a collagen anchoring module and a target proteolysis-responsive isothermal amplification sensor module, can be anchored in the collagen-rich TME and respond to the target protease in situ and generate amplified signals through rolling cycle amplification of tandem fluorescent RNAs. Taking matrix metalloproteinase 2 (MMP-2), a tumor-associated protease, as the model, the feasibility of PNCP was demonstrated for the in situ detection of MMP-2 activity in 3D tumor spheroids. Moreover, in situ in vivo mapping of MMP-2 activity was also achieved in a metastatic solid tumor model with high sensitivity, providing a useful tool for evaluating tumor metastasis and distinguishing highly aggressive forms of tumors.


Assuntos
Metaloproteinase 2 da Matriz , Neoplasias , Humanos , Metaloproteinase 2 da Matriz/genética , Peptídeo Hidrolases , Colágeno , Sondas de Ácido Nucleico , Microambiente Tumoral
7.
Chem Sci ; 14(43): 12182-12193, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37969575

RESUMO

Monitoring the spatiotemporal dynamics of cancer biomarkers within the tumor microenvironment (TME) is critical to understanding their roles in tumorigenesis. Here, we reported a multifunctional fusion protein (collagen-binding domain and duck circovirus tag fused to mCherry, CBD-mCherry-DCV) capable of binding collagen with high affinity and covalently binding specific nucleic acids with exceptional efficiency. We then constructed a chimeric protein-nucleic acid nanodevice (CPNN) using CBD-mCherry-DCV and an aptamer-based sensing module to enable spatially controlled ratiometric imaging of cancer biomarkers in the TME. The collagen-anchoring module CBD-mCherry-DCV allowed specific immobilization of CPNN on 3D multicellular tumor spheroids, enabling the sensing module to achieve "off-on" fluorescence imaging of cancer biomarkers upon specific target recognition by an aptamer. Taking advantage of the constant fluorescence signal of mCherry and the activatable fluorescence response of Cy5 to specific cancer biomarkers, the detection sensitivity and reliability of CPNN were improved by self-calibrating the signal intensity. Specifically, CPNN enabled ratiometric fluorescence imaging of varying concentrations of exogenous PDGF-BB and ATP in tumor spheroids with a high signal-to-background ratio. Furthermore, it allowed the visual monitoring of endogenous PDGF-BB and ATP released from cells. Overall, this study demonstrates the potential of the nanodevice as a versatile approach for the visualization and imaging of cancer biomarkers in the TME.

10.
J Cardiovasc Dev Dis ; 10(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37754798

RESUMO

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

11.
Cancer Med ; 12(18): 18568-18577, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37641492

RESUMO

PURPOSE: The prognostic factors for diffuse large B-cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. METHODS: We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. RESULTS: In all patients with bulky mass DLBCL, the 1-year and 3-year OS rates were 72.7% and 57.1%, respectively, and the 1-year and 3-year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression-free survival (PFS; p = 0.001) than the non-MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3-5 (OS: p = 0.011; PFS: p < 0.001), Ann Arbor stage 3-4 (OS: p = 0.014; PFS: p < 0.001) and GCB subtype (OS: p = 0.014; PFS: p = 0.010). Consolidation radiotherapy improved OS and PFS in patients with bulky mass DLBCL (OS: p = 0.008; PFS: p = 0.004) as well as in those with MYC overexpression (OS: p = 0.001; PFS: p = 0.001). The prognostic value of MYC overexpression was maintained in a multivariate model adjusted for the International Prognostic Index. CONCLUSION: MYC overexpression is a poor predictor for bulky mass DLBCL patients. Consolidation radiotherapy for residual disease after induction therapy may improve outcomes for patients with bulky mass DLBCL.

12.
Clin. transl. oncol. (Print) ; 25(8): 2438-2450, aug. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-222421

RESUMO

Background The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. Methods By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital’s clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. Results The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients’ tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). Conclusions In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development (AU)


Assuntos
Humanos , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/imunologia , Biomarcadores Tumorais , Microambiente Tumoral , Albuminas/uso terapêutico , Citocinas/metabolismo , Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia , Prognóstico
13.
Ann Hematol ; 102(10): 2765-2777, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37491631

RESUMO

Bruton's tyrosine kinase inhibitor (BTKi) has revolutionized the treatment of B-cell lymphomas. However, BTKi-related hematological toxicity hinders treatment continuity and may further affect clinical efficacy. To identify risk factors and predict the likelihood of BTKi-related hematological toxicities, we constructed and validated a prediction model for severe hematological toxicity of BTKi. Approved by the hospital medical science research ethics committee (No. M2022427), we collected real-world data in patients treated with BTKi from a Lymphoma Research Center in China. The outcome of interest was severe hematological toxicity caused by BTKi. 36 candidate variables were categorized into demographics, diagnostic and treatment information, laboratory data, and medical history. The study sample was randomly divided into training (70%) and validation (30%) sets. We developed and compared the performance of various modelling methods, including decision tree (DT), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and logistic regression (LR). Finally, we constructed a Web-calculator of the optimal model to estimate the risk of hematological toxicity. This study was designed, conducted and reported strictly in compliance with the TRIPOD checklist. Data from a total 121 patients were included [median age, 65 years (range, 56-73 years); 74 (61.15%) men; 47 (38.84%) severe hematological toxicity]. The XGBoost model demonstrated better overall properties than other models, achieving high discrimination (AUC: 0.671; accuracy: 0.730; specificity: 0.913) and clinical benefit. The following 10 variables were used to develop the XGBoost model: white blood cell count (WBC), neutrophil count (Neut), red blood cell count (RBC), platelet count (PLT), fibrinogen (Fib), total protein (TP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gender and type of BTKi. SHAP values demonstrated insightful associations between these variables and hematological toxicity. Finally, to facilitate clinical and research use, we also deploy the XGBoost model on a web-calculator for free access. The XGBoost model with promising accuracy was developed to predict the severe hematological toxicity of BTKi. It helps to strengthen the proactive monitoring and management of patients with hematological toxicity, and thus achieve long-term continuous BTKi treatment.


Assuntos
Pesquisa Biomédica , Masculino , Humanos , Idoso , Feminino , Aspartato Aminotransferases , China , Fibrinogênio , Hospitais
14.
Nat Commun ; 14(1): 3826, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37429843

RESUMO

We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.


Assuntos
Estudo de Associação Genômica Ampla , Insuficiência Cardíaca , Humanos , Análise da Randomização Mendeliana , Proteômica , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética
15.
J Med Chem ; 66(12): 8011-8029, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37272653

RESUMO

Bombesin receptor subtype-3 (BB3, BRS-3) is an orphan Gαq protein-coupled receptor. The characterization of novel synthetic ligands for BB3 is an alternative and attractive strategy to study its diverse physiological functions. Here, we uncovered the intimate pairing of DMAKO-00 and its derivatives with BB3. Dimethyl shikonin oxime 5a (DSO-5a) was identified as the most potent agonist for BB3 (pEC50 = 8.422 in IP-1 accumulation), which was 898-fold more potent than DMAKO-00. Importantly, without brain penetration, DSO-5a improved glucose tolerance in C57BL/6 mice through BB3 and ameliorated glucose homeostasis in diabetic db/db mice. We further revealed that DSO-5a upregulated PPAR-gamma activity via BB3 through a quantitative proteomics approach. Collectively, our study demonstrated that DSO-5a, a representative compound of DMAKO-00 derivatives, is a potent, selective, and low-brain-penetrating agonist for BB3, and BB3 is a promising treatment target for type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Receptores da Bombesina , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos Endogâmicos C57BL , Glucose , Bombesina
16.
J Proteome Res ; 22(7): 2364-2376, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37368948

RESUMO

Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that is involved in a variety of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. In this study, a quantitative phosphoproteomics approach was employed to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. The lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of BRS3, for different durations. Harvested cellular proteins were digested and phosphopeptides were enriched by immobilized titanium (IV) ion affinity chromatography (Ti4+-IMAC) for label-free quantification (LFQ) analysis. A total of 11,938 phosphopeptides were identified, corresponding to 3,430 phosphoproteins and 10,820 phosphosites. Data analysis revealed that 27 phosphopeptides corresponding to six proteins were involved in the Hippo signaling pathway, which was significantly regulated by BRS3 activation. Verification experiments demonstrated that downregulation of the Hippo signaling pathway caused by BRS3 activation could induce the dephosphorylation and nucleus localization of the Yes-associated protein (YAP), and its association with cell migration was further confirmed by kinase inhibition. Our data collectively demonstrate that BRS3 activation contributes to cell migration through downregulation of the Hippo signaling pathway.


Assuntos
Via de Sinalização Hippo , Receptores da Bombesina , Receptores da Bombesina/metabolismo , Fosfopeptídeos , Transdução de Sinais/fisiologia , Movimento Celular , Fosfoproteínas/metabolismo
17.
Mol Cell Proteomics ; 22(8): 100611, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37391046

RESUMO

Profiling the nucleic acid-binding proteins (NABPs) during aging process is critical to elucidate its roles in biological systems as well as transcriptional and translational regulation. Here, we developed a comprehensive strategy to survey the NABPs of mouse immune organs by using single cell preparation and selective capture technology-based proteomics. Our approach provided a global view of tissue NABPs from different organs under normal physiological conditions with extraction specificity of 70 to 90%. Through quantitative proteomics analysis of mouse spleen and thymus at 1, 4, 12, 24, 48, and 72 weeks, we investigated the molecular features of aging-related NABPs. A total of 2674 proteins were quantified in all six stages, demonstrating distinct and time-specific expression pattern of NABPs. Thymus and spleen exhibited unique aging signatures, and differential proteins and pathways were enriched across the mouse lifespan. Three core modules and 16 hub proteins associated with aging were revealed through weighted gene correlation network analysis. Significant candidates were screened for immunoassay verification, and six hub proteins were confirmed. The integrated strategy pertains the capability to decipher the dynamic functions of NABPs in aging physiology and benefit further mechanism research.


Assuntos
Ácidos Nucleicos , Proteoma , Animais , Camundongos , Proteoma/genética , Envelhecimento/genética , Perfilação da Expressão Gênica
18.
J Glob Antimicrob Resist ; 34: 30-38, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315738

RESUMO

OBJECTIVES: The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China. METHODS: The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality. RESULTS: In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD) = 1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD = 23.76%, 95% CI [20.23%, 27.3%]; MD = 69.32%, 95% CI [64.85%, 73.8%]; and MD = 29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias. CONCLUSION: Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Metronidazol/farmacologia , Claritromicina/farmacologia , Levofloxacino/farmacologia , Helicobacter pylori/genética , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/tratamento farmacológico , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia
19.
Environ Sci Pollut Res Int ; 30(33): 80279-80292, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37296248

RESUMO

The environment and human health are in danger due to the long-term enrichment and buildup of organic pesticides, dyes, and harmful microbes in wastewater. The development of functional materials that are efficient for treating wastewater remains a significant problem. Eco-friendly hexagonal spindle-shaped Fe-MOFs (Hs-FeMOFs) were created in this study under the influence of cationic copolymer (PMSt). The mechanism of crystal growth and development of its unique morphology were described after looking into impact factors for the ideal circumstances and being characterized by XRD, TEM, XPS, and other techniques. It revealed that Hs-FeMOFs possess an enormous supply of adsorption active sites, a strong electropositivity, and the nanometer tip. Then, typical organic pollutants, such as herbicides and mixed dyes, as well as biological pollutants bacteria, were chosen to assess its efficacy in wastewater treatment. It was discovered that the pendimethalin could be quickly removed in wastewater and the removal rate reached 100% within 10 min. In separation of mixed dyes, the retention rate of malachite green (MG) reached 92.3% in 5 min and with a minimum inhibitory concentration of 0.8 mg/mL and demonstrated strong activity due to the presence of cationic copolymers. In actual water matrix, Hs-FeMOF could also play excellent adsorption and antibacterial activity. In summary, a novel, environmentally friendly MOF material with good activity was successfully created by cationic copolymer induction. It offers a fresh approach to develop functional materials in wastewater treatment.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Purificação da Água , Humanos , Águas Residuárias , Corantes/química , Purificação da Água/métodos , Polímeros , Adsorção , Poluentes Químicos da Água/química
20.
Kidney Int Rep ; 8(5): 1076-1086, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37180517

RESUMO

Introduction: People with HIV (PWH) of African ancestry have faster decline of kidney function and faster progression to end-stage renal disease than PWH of European ancestry. DNA methylation have been associated with kidney function in the general population, however, their relationships are unclear for PWH of African ancestry. Methods: We performed epigenome-wide association studies (EWAS) of estimated glomerular filtration rate (eGFR) among PWH of African ancestry in 2 subsets of the Veterans Aging Cohort Study cohort (N = 885), followed by a meta-analysis to combine the results. Replication was conducted among independent African American samples without HIV. Results: DNA methylation sites cg17944885 near Zinc Finger Family Member 788 (ZNF788) and Zinc Finger Protein 20 (ZNF20), and cg06930757 in SHANK1 were significantly associated with eGFR among PWH of African ancestry (false discovery rate < 0.05). DNA methylation site cg17944885 was also associated with eGFR among different populations including African Americans without HIV. Conclusions: Our study attempted to address an important gap in the literature and to understand the role of DNA methylation in renal diseases in PWH of African ancestry. Replication of cg17944885 among different populations suggests there may be a common pathway for renal diseases progression among PWH and people without HIV, and across different ancestral groups. Our results suggest that genes ZNF788/ZNF20 and SHANK1 could be involved in a pathway linking DNA methylation to renal diseases among PWH and are worth further investigation.

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