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1.
Biomed Pharmacother ; 179: 117366, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232384

RESUMO

The RNA N6-methyladenosine (m6A) regulator METTL3 is an important regulatory gene in various progressive processes of prostate cancer (PCa). METTL3 inhibitors have been reported to possess potent tumor suppression capacity in some cancer types. Nevertheless, the detailed influence and mechanism of METTL3 inhibitors on PCa progression and their potential synergy with other drugs are poorly understood. In this study, we demonstrated that METTL3 was overexpressed and associated with poor survival in most PCa patients. METTL3 inhibitor STM2457 reduced m6A levels of PCa cells, thus inhibiting their proliferation, colony formation, migration, invasion, and stemness in vitro. Furthermore, STM2457 suppressed PCa progression in both the CDX and PDX models in vivo. MeRIP-seq analysis coupled with biological validation revealed that STM2457 influenced multiple biological processes in PCa cells, mainly through the IGFBP3/AKT pathway. We also proved that STM2457 induced DNA damage and showed synergistic anti-PCa effects with the PARP inhibitor olaparib both in vitro and in vivo. All in all, this work provides a novel therapeutic strategy for targeting RNA m6A modifications for the treatment of PCa and provides a meaningful reference for further clinical trials.


Assuntos
Proliferação de Células , Progressão da Doença , Sinergismo Farmacológico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Metiltransferases , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Metiltransferases/metabolismo , Metiltransferases/antagonistas & inibidores , Animais , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Adenosina/análogos & derivados , Adenosina/farmacologia
2.
Heliyon ; 10(17): e36954, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39281461

RESUMO

Background: Life's Essential 8 (LE8), an indicator of cardiovascular health (CVH), can predict overall and cardiovascular mortality in the general population. Considering that cancer survivors have a higher risk of cardiovascular disease (CVD), our study aimed to investigate the association between LE8 and the prognosis of cancer survivors. Methods: A total of 2191 cancer survivors were included from the National Health and Nutrition Examination Survey (2005-2018). LE8 scores, derived from eight individual metrics, were categorized into three groups: low (0-49), moderate (50-79), and high (80-100). Cox regression analysis, nonlinear analysis, sensitivity analysis, and subgroup analysis were conducted to explore the association between LE8 scores and mortality risks, adjusting for potential confounders. Results: During a median follow-up of six years, 479 deaths were recorded, including 118 CVD events and 156 cancer events. LE8 scores showed an inverse linear relationship with all-cause and cardiovascular mortality. A 10-point increase in LE8 scores was associated with a 25 % reduction in all-cause mortality (hazard ratio [HR], 0.75; 95 % CI, 0.66-0.85) and a 29 % reduction in cardiovascular mortality (HR, 0.71; 95 % CI, 0.57-0.89). Additionally, moderate CVH was linked to a lower risk of all-cause mortality (HR, 0.55; 95 % CI, 0.37-0.81), while high CVH was associated with an even lower risk (HR, 0.35; 95 % CI, 0.19-0.68). Similarly, moderate CVH demonstrated a decreased risk of cardiovascular mortality (HR, 0.31; 95 % CI, 0.15-0.63), with high CVH showing an even lower risk (HR, 0.23; 95 % CI, 0.09-0.58). However, LE8 scores was not associated with cancer-specific mortality. Conclusions: A higher LE8 score was independently associated with a decreased risk of both all-cause and cardiovascular mortality in cancer survivors, underscoring the significance of optimizing CVH during the survivorship phase of cancer care.

4.
Lab Chip ; 24(7): 1977-1986, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38372394

RESUMO

The transportation and control of microfluidics have an important influence on the fields of biology, chemistry, and medicine. Pump systems based on the electrocapillary effect and room-temperature liquid metal droplets have attracted extensive attention. Flow rate is an important parameter that reflects the delivery performance of the pump systems. In the systems of previous studies, cylindrical structures are mostly used to constrain the droplet. The analysis and quantitative description of the influence of voltage frequency, alternating voltage, direct current voltage bias, and solution concentration on the flow rate are not yet comprehensive. Furthermore, the systems are driven by only one droplet, which limits the increase in flow rate. Therefore, a pump with a cuboid structure is designed and the droplet is bound by pillars, and the flow rate of the pump is increased by more than 200% compared with the cylindrical pump. For this structure, the mechanism of various factors on the flow rate is analyzed. To further enhance the flow rate, a pump system with multi-droplets is proposed. Moreover, the expression of flow velocity of the solution on the surface of each droplet and the relationship between the flow rate, alternating voltage, and the number of droplets are deduced. Finally, the potential of applying the multi-droplet cuboid pump system in drug delivery and analytical chemistry is demonstrated. Additionally, the core of the pump, the droplet area, is modularized, which breaks the overall structural limitations of the liquid metal pump and provides ideas for pump design.

5.
Eur J Med Res ; 29(1): 112, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336764

RESUMO

BACKGROUND: Bladder cancer is a common malignancy of the urinary system, and the survival rate and recurrence rate of patients with muscular aggressive (MIBC) bladder cancer are not ideal. Hypoxia is a pathological process in which cells acquire special characteristics to adapt to anoxic environment, which can directly affect the proliferation, invasion and immune response of bladder cancer cells. Understanding the exact effects of hypoxia and immune-related genes in BLCA is helpful for early assessment of the prognosis of BLCA. However, the prognostic model of BLCA based on hypoxia and immune-related genes has not been reported. PURPOSE: Hypoxia and immune cell have important role in the prognosis of bladder cancer (BLCA). The aim of this study was to investigate whether hypoxia and immune related genes could be a novel tools to predict the overall survival and immunotherapy of BLCA patients. METHODS: First, we downloaded transcriptomic data and clinical information of BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A combined hypoxia and immune signature was then constructed on the basis of the training cohort via least absolute shrinkage and selection operator (LASSO) analysis and validated in test cohort. Afterwards, Kaplan-Meier curves, univariate and multivariate Cox and subgroup analysis were employed to assess the accuracy of our signature. Immune cell infiltration, checkpoint and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to investigate the immune environment and immunotherapy of BLCA patients. Furthermore, we confirmed the role of TFRC in bladder cancer cell lines T24 and UMUC-3 through cell experiments. RESULTS: A combined hypoxia and immune signature containing 8 genes were successfully established. High-risk group in both training and test cohorts had significantly poorer OS than low-risk group. Univariate and multivariate Cox analysis indicated our signature could be regarded as an independent prognostic factor. Different checkpoint was differently expressed between two groups, including CTLA4, HAVCR2, LAG3, PD-L1 and PDCD1. TIDE analysis indicated high-risk patients had poor response to immunotherapy and easier to have immune escape. The drug sensitivity analysis showed that high-risk group patients were more potentially sensitive to many drugs. Meanwhile, TFRC could inhibit the proliferation and invasion ability of T24 and UMUC-3 cells. CONCLUSION: A combined hypoxia and immune-related gene could be a novel predictive model for OS and immunotherapy estimation of BLCA patients and TFRC could be used as a potential therapeutic target in the future.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Algoritmos , Linhagem Celular
6.
Sci Rep ; 14(1): 3335, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336964

RESUMO

Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.


Assuntos
Arteriosclerose , Cicloexilaminas , Ferroptose , Proteína HMGB1 , Fenilenodiaminas , Humanos , Células Endoteliais , Interleucina-6 , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2 , Fator de Necrose Tumoral alfa , Inflamação , Oxirredução , Ferro
7.
Eur J Med Res ; 29(1): 52, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217031

RESUMO

BACKGROUND: Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly. METHODS: We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines. RESULTS: We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (CA and CB) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells. CONCLUSION: We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments.


Assuntos
Anoikis , Neoplasias da Bexiga Urinária , Humanos , Anoikis/genética , Neoplasias da Bexiga Urinária/genética , Algoritmos , Linhagem Celular , Prognóstico , Proteína A7 Ligante de Cálcio S100
8.
Artigo em Inglês | MEDLINE | ID: mdl-37813096

RESUMO

Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life's Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005-2018). Life's Essential 8 scores were categorized into low, moderate, and high groups. PhenoAge, measured through clinical laboratory blood chemistries, served as a marker of biological aging. Weighted linear regression analyses were performed to assess the association between LE8 scores and PhenoAgeAceel. In the multivariable linear regression, LE8 scores were significantly and inversely associated with PhenoAgeAccel, showing a decreased risk in the moderate CVH group (ß -2.98; 95% CI -3.29, -2.66) and high CVH group (ß -4.72; 95% CI -5.08, -4.35) compared to the low CVH group. When treated as a continuous variable, each 10-point increase in LE8 scores corresponded to a 1.14-year decrease in PhenoAge (ß -1.14; 95% CI -1.21, -1.06). Among the 8 individual components in LE8, 7 exhibited a significant negative correlation with PhenoAgeAccel, except for blood lipids. Additionally, mediation analysis revealed that oxidative stress biomarkers, including γ-glutamyltransferase, bilirubin, and uric acid, collectively mediated 17.1% of the associations between LE8 scores and PhenoAgeAccel (p < .001). Higher LE8 scores, representing ideal CVH, are significantly related to a deceleration in PhenoAge, and oxidative stress biomarkers may play a mediating role in this relationship.


Assuntos
Doenças Cardiovasculares , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Fatores de Risco , Envelhecimento , Biomarcadores , Estresse Oxidativo
9.
Langmuir ; 39(51): 18825-18833, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38096374

RESUMO

The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes. In addition, the energy analysis of the coalescence-induced droplet jumping reveals that the two primary factors influencing the jumping are the relative size and position of the droplets and micropillars. Further numerical simulations find that the wedge-shaped micropillars cause an asymmetric distribution of pressure within the droplet and at the solid-liquid contact surface, which generates an unbalanced force driving the droplet in the gradient direction of the wedge-shaped micropillar, causing the droplet to jump off the surface with both vertical and gradient-direction velocities. The capacity of the wedge-shaped micropillar surface to transport droplets in the gradient direction increases and then decreases as the relative size of the droplets and micropillars increases. The relative position of the droplet center-of-mass line perpendicular to the bottom edge of the wedge micropillars' trapezoidal shape is more favorable for droplet transport. This work reveals the influence mechanism of surface structure on the velocity and direction of droplet jumping, and the results can guide the microstructure design of superhydrophobic surfaces, which has significant implications for the application of droplet jumping.

10.
Chem Biodivers ; 20(11): e202300999, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37933979

RESUMO

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.


Assuntos
Dendrobium , NF-kappa B , NF-kappa B/metabolismo , Macrófagos Alveolares/metabolismo , Transdução de Sinais , Anti-Inflamatórios/farmacologia
11.
Front Oncol ; 13: 1187677, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901313

RESUMO

Purpose: This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Method: This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score. The variable importance and minimum depth methods were used to screen for significant variables, and univariable and multivariable logistic regression models applied to investigated the relationships between significant variables and postoperative complications. Survival differences between groups were analyzed using Kaplan-Meier plots and log-rank tests. Cox proportional hazards regression was used to evaluate risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Further, we developed a nomogram based on clinicopathological features and the sFI. The area under the curve (AUC), Harrel's concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Result: Of 333 cases identified, 31.2% experienced a Clavien-Dindo grade of 2 or greater complication. Random forest-logistic regression modeling showed that sFI significantly influenced the incidence of postoperative complications in older patients (AUC= 0.756). Compared with patients with low sFI score, those with high sFI scores had significantly lower OS and CSS (p < 0.001). Across all patients, the random survival forest-Cox regression model revealed that sFI score was an independent prognostic factor for OS and CSS, with AUC values of 0.815 and 0.823 for predicting 3-year OS and CSS, respectively. The nomogram developed was clinically valuable and had good ability to discriminate abilities for high-risk patients. Further, we developed a survival risk classification system that divided all patients into high-, moderate-, and low-risk groups based on total nomogram points for each patient. Conclusion: A simple five-item frailty index may be considered a prognostic factor for the prognosis and postoperative complications of UTUC following RNU. By using this predictive model, clinicians may increase their accuracy in predicting complications and prognosis and improve preoperative decision-making.

12.
Chin Med J (Engl) ; 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37690993

RESUMO

BACKGROUND: Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18F-prostate specific membrane antigen positron emission tomography/computerized tomography (18F-PSMA PET/CT) has several advantages over 68Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18F-PSMA PET/CT for lymph node staging in medium/high-risk PCa. METHODS: We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses. RESULTS: A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89). CONCLUSIONS: 18F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68Ga-PSMA PET/CT. REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

13.
Sci Total Environ ; 903: 166197, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-37567311

RESUMO

Synergetic reduction of pollution and carbon is a key strategy for the fundamental improvement of ecological and environmental quality and carbon neutrality. Solid waste resource utilization can reduce the secondary pollution caused by conventional solid waste disposal and presents evident environmental potential. Based on the comparable system boundaries, this study adopts life cycle assessment (LCA) to compare the environmental impact of three fly ash utilization paths. The synergy index is then defined according to six environmental impact indicators to quantitatively evaluate the synergetic effects of carbon emission and pollutant reduction. The results confirm the possibility of fly ash resource utilization for synergetic pollution and carbon reduction and demonstrate the synergetic emission reduction potential of the solid waste resource utilization supply chain. This study is both an application of the life cycle assessment model in the solid waste utilization and disposal field and provides insight into the pathway of pollution and carbon reduction in China.

14.
Int J Biol Sci ; 19(11): 3293-3306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37496990

RESUMO

Background: As a transcription factor, Zic family member 2 (ZIC2) has been involved in more and more studies of tumorigenesis, which has been proved by our research team to be an effective prognostic marker for Pan-cancer. However, the prognosis, tumor promoting effect and regulatory mechanism of ZIC2 in clear cell renal cell carcinoma (ccRCC) are still unknown. Methods: The potential clinical significance of ZIC2 was evaluated by bioinformatics analysis using data from TCGA, GEO, and ArrayExpress data sets. WB and IHC were used to detect ZIC2 expression in tumors and adjacent tissues. CCK-8, EdU, colony formation, cell cycle, wound healing, transwell, subcutaneous xenograft, and lung metastasis models were used to detect the biological function of ZIC2. The regulatory mechanism of ZIC2 was confirmed by data of RNA-seq, ATAC-seq, MS-PCR, Chip-PCR, and luciferase reporter experiments. Results: ZIC2 was markedly upregulated and correlated with poor clinicopathological features in ccRCC. Knockdown of ZIC2 resulted in reduced cell proliferation, invasion, migration, induction of G2/M phase arrest, and reduced tumor formation and lung metastasis in nude mice. The opposite was observed after overexpression. Mechanistically, the high expression of ZIC2 is regulated by hypomethylation and high H3K4Me3 in the promoter region, as well as positive transcriptional regulation by FOXM1. And then, ZIC2 transcriptase-positively regulates UBE2C and activates AKT/mTOR signaling pathway to promote tumor malignant progression. Conclusion: This study reveals that FOXM1-ZIC2-UBE2C-mTOR signaling axis promotes the progression of ccRCC, which can be used as a prognostic indicator and potential therapeutic target.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Carcinoma/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Renais/metabolismo , Neoplasias Pulmonares/genética , Camundongos Nus , Fenótipo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Enzimas de Conjugação de Ubiquitina/genética
15.
Bioresour Technol ; 386: 129507, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37468003

RESUMO

Heterotrophic nitrification-aerobic denitrification (HN-AD) process was achieved in a moving bed biofilm reactor after 180-days acclimation using PCL as carbon source for low C/N wastewater treatment. A novel HN-AD strain, JQ-H3, with ability of PCL degradation was augmented to improve nitrogen removal. TN removal efficiencies of 82.31%, 90.05%, and 93.16% were achieved in the augmented reactor (R2), at different HRTs of 24 h, 20 h, and 16 h, while in the control reactor (R1), the TN removal efficiencies were 59.24%, 74.61%, and 76.68%. The effluent COD in R2 was 10.17 mg/L, much lower than that of 42.45 mg/L in R1. Microbial community analysis revealed that JQ-H3 has successfully proliferated with a relative abundance of 4.79%. Relative abundances of functional enzymes of nitrogen cycling remarkably increased due to bioaugmentation based on the analysis of PICRUSt2. This study provides a new approach for enhancing nitrogen removal in low C/N sewage treatment via the HN-AD process.


Assuntos
Desnitrificação , Águas Residuárias , Pseudomonas , Nitrogênio/análise , Carbono , Reatores Biológicos , Nitrificação , Biofilmes , Aceleração
16.
Langmuir ; 39(27): 9315-9324, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37377336

RESUMO

Gallium-based liquid metal is a new class of material that has attracted extensive attention due to its excellent deformation characteristics and great potential in applications. Based on the deformation characteristics of liquid metal droplets, researchers have developed many oscillation systems composed of gallium indium tin alloy (GaInSn) droplet and graphite, or aluminum-doped gallium indium alloy (Al-GaIn24.5) droplet and iron, and so on. Rather than the oxidation and deoxidation mechanisms used in previous systems, an oscillation system that can achieve gallium indium alloy (EGaIn) droplet oscillation with the frequency of 0-29 Hz is designed depending on the interactions between the electric field, pillars, sodium hydroxide, and the droplet. The forces on the droplet are analyzed specifically, which have a great influence on droplet deformation. Additionally, the effects of factors such as voltage, the concentration of sodium hydroxide (NaOH) solution, and droplet size on the droplet oscillation are elucidated based on the force analysis, enabling the flexible control of the oscillation frequency and amplitude of the droplet. This work provides a new perspective on the design of oscillation systems and further enhances our understanding of the deformation of gallium-based liquid metal droplets.

17.
BMC Cancer ; 23(1): 574, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349696

RESUMO

PURPOSE: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). METHOD: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. RESULT: According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. CONCLUSION: The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Sistema Urinário , Neoplasias Urológicas , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/patologia , Prognóstico , Neoplasias Urológicas/patologia , Neoplasias da Bexiga Urinária/patologia , Estudos Retrospectivos , Neoplasias Renais/patologia , Neoplasias Ureterais/patologia , Inflamação/patologia , Sistema Urinário/patologia , Aprendizado de Máquina
18.
J Colloid Interface Sci ; 649: 290-301, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37352560

RESUMO

HYPOTHESIS: Most droplets on high-efficiency condensing surfaces have radii of less than 100 µm, but conventional droplet transport methods (such as wettability-gradient surfaces and structural-curvature-gradient surfaces) that rely on the unbalanced force of three-phase lines can only transport millimeter-sized droplets efficiently. Regulating high-speed directional transport of condensate droplets is still challenging. Therefore, we present a method for condensate droplet transportation, based on the reaction force of the superhydrophobic saw-tooth surfaces to the liquid bridge, the condensate droplets could be transported at high speed and over long distances. EXPERIMENTS: The superhydrophobic saw-tooth surfaces are fabricated by femtosecond laser ablation and chemical etching. Condensation experiments and luminescent particle characterization experiments on different surfaces are conducted. Aided by the theoretical analysis, we illustrate the remarkable performance of condensate droplet transportation on saw-tooth surfaces. FINDINGS: Compared with conventional methods, our method improves the transport velocity and relative transport distance by 1-2 orders of magnitude and achieves directional transport of the smallest condensate droplet of about 2 µm. Furthermore, the superhydrophobic saw-tooth surfaces enable multi-hop directional jumping of condensate droplets, leading to cross-scale increases in transport distances from microns to decimeters.

19.
Int. braz. j. urol ; 49(3): 359-371, may-June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1440259

RESUMO

ABSTRACT Purpose Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. Methods In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). Results The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. Conclusions PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.

20.
Int Braz J Urol ; 49(3): 359-371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37115180

RESUMO

PURPOSE: Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. METHODS: In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). RESULTS: The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. CONCLUSIONS: PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética , Antígeno Prostático Específico , Biópsia Guiada por Imagem , Próstata/diagnóstico por imagem , Próstata/patologia , Estudos Retrospectivos
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