Association between oxidative balance score and kidney stones: data from the national health and nutrition examination survey (NHANES).

PURPOSE: Some studies have found that the pathological formation of kidney stones is closely related to injury and inflammatory response. Behaviors such as dietary composition, physical activity, obesity and smoking can all affect the body's oxidative stress levels. In order to evaluate the effects of various diets and lifestyles on the body's oxidative and antioxidant systems, an oxidative balance score was developed. To investigate whether the OBS is associated with the development of kidney stones. METHODS: Data were taken from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, followed by retrospective observational studies. The association between kidney stones and OBS was analyzed using survey-weighted logistic regression by adjusting for demographics, laboratory tests, and medical comorbidity covariates. The oxidative balance score is calculated by screening 16 nutrients and 4 lifestyle factors, including 5 prooxidants and 15 antioxidants, based on prior information about the relationship between oxidation levels in the body and nutrients or lifestyle factors. RESULTS: A total of 26,786 adult participants were included in the study, of which 2,578, or 9.62%, had a history of nephrolithiasis. Weighted logistic regression analysis found an association between OBS and kidney stones. In the fully tuned model, i.e., model 3, the highest quartile array of OBS was associated with the lowest quartile array of OBS (OR = 0.73 (0.57, 0.92)) with the risk of kidney stone (p = 0.01), and was statistically significant and remained relatively stable in each model. At the same time, the trend test in the model is also statistically significant. With the increase of OBS, the OR value of kidney stones generally tends to decrease. CONCLUSIONS: There is an inverse correlation between OBS and kidney stone disease. At the same time, higher OBS suggests that antioxidant exposure is greater than pro-oxidative exposure in diet and lifestyle, and is associated with a lower risk of kidney stones.

Cotransport of microplastics and sulfanilamide antibiotics in groundwater: The impact of MP/SA ratio and aquifer media.

The aim of this study was to investigate the effects of the aquifer media, structure type, and initial concentration ratio of contaminants on the cotransport behavior of microplastics (MPs) and sulfanilamide antibiotics (SAs) through a series of one-dimensional column experiments in groundwater. Under a single suspension system, the relative mass recovery rates of fine sand, medium sand, and coarse sand were 25.65%, 37.50%, and 57.91%, respectively. The breakthrough curve of MPs showed a weak and slow upward trend, indicating that the migration of MPs in aqueous media is mainly blocked by the surface. The migration results of different structure type on SAs (ST, SM, SM2, SMX) in a single suspension system indicated that the deposition rate coefficients (kc) of the four SAs were 1.23 × 10-1, 9.09 × 10-2, 1.11 × 10-1, and 8.87 × 10-2. Under a binary suspension system (MPs:ST = 1:1), the maximum effluent concentration (MEC) of MPs in fine sand, medium sand, and coarse sand increased to 0.52, 0.64, and 0.88, respectively, and the relative mass recovery rates of ST were 22.79%, 23.59%, 20.25%. This results show that the coexistence of MPs and SAs significantly promotes the migration of MPs and inhibits that of SAs. It is mainly because of their carrier action, adsorption sites and additional deposit sites for MPs through SAs pre-deposition on media. When the initial concentration ratio was 2:1, the particles had the highest Zeta potential (-48.3 mV) and the highest potential barrier (3200 kBT), leading to the formation of complex aggregates (MPs-SAs-MPs) owing to the aggregation of colloidal MPs. The increase in the volume and number of MPs-SAs co-aggregates on the surface of the media as the initial concentration of MPs increases, which was mainly due to the disappearance of surface blocking effect and the occurrence of filtering maturation effect.

Generating Daily Soil Moisture at 16 m Spatial Resolution Using a Spatiotemporal Fusion Model and Modified Perpendicular Drought Index.

Soil moisture (SM) is an important parameter in land surface processes and the global water cycle. Remote sensing technologies are widely used to produce global-scale SM products (e.g., European Space Agency's Climate Change Initiative (ESA CCI)). However, the current spatial resolutions of such products are low (e.g., >3 km). In recent years, using auxiliary data to downscale the spatial resolutions of SM products has been a hot research topic in the remote sensing research area. A new method, which spatially downscalesan SM product to generate a daily SM dataset at a 16 m spatial resolution based on a spatiotemporal fusion model (STFM) and modified perpendicular drought index (MPDI), was proposed in this paper. (1) First, a daily surface reflectance dataset with a 16 m spatial resolution was produced based on an STFM. (2) Then, a spatial scale conversion factor (SSCF) dataset was obtained by an MPDI dataset, which was calculated based on the dataset fused in the first step. (3) Third, a downscaled daily SM product with a 16 m spatial resolution was generated by combining the SSCF dataset and the original SM product. Five cities in southern Hebei Province were selected as study areas. Two 16 m GF6 images and nine 500 m MOD09GA images were used as auxiliary data to downscale a timeseries 25 km CCI SM dataset for nine dates from May to June 2019. A total of 151 in situ SM observations collected on 1 May, 21 May, 1 June, and 11 June were used for verification. The results indicated that the downscaled SM data with a 16 m spatial resolution had higher correlation coefficients and lower RMSE values compared with the original CCI SM data. The correlation coefficients between the downscaled SM data and in situ data ranged from 0.45 to 0.67 versus 0.33 to 0.54 for the original CCI SM data; the RMSE values ranged from 0.023 to 0.031 cm3/cm3 versus 0.027 to 0.032 cm3/cm3 for the original CCI SM data. The findings described in this paper can ensure effective farmland management and other practical production applications.

Development and validation of a predictive model for determining clinically significant prostate cancer in men with negative magnetic resonance imaging after transrectal ultrasound-guided prostate biopsy.

BACKGROUND: The interpretation of negative magnetic resonance imaging (MRI) screening results for clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade ≥group 2) is debatable and poses a clinical dilemma for urologists. No nomograms have been developed to predict csPCa in such populations. In this study, we aimed to develop and validate a model for predicting the probability of csPCa in men with negative MRI (PI-RADS score 1-2) results after transrectal ultrasound-guided systematic prostate biopsy. METHODS: The development cohort consisted of 728 patients with negative MRI results who underwent subsequent prostate biopsy at our center between January 1, 2014 and December 31, 2017. The patients' clinicopathologic data were recorded. The Lasso regression was used for data dimension reduction and feature selection, then multivariable binary logistic regression was used to build a predictive model with regression coefficients. The model was validated in an independent cohort of 334 consecutive patients from January 1, 2018 and June 30, 2020. The performance of the predictive model was assessed with respect to discrimination, calibration, and decision curve analysis. RESULTS: The predictors incorporated in this model included age, history of previous negative prostate biopsy, prostate specific antigen density (PSAD), and lower urinary tract symptoms, with PSAD being the strongest predictor. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.816-0.933) and good calibration (unreliability test, p = .540). Decision curve analysis demonstrated that the model was clinically useful. CONCLUSION: This study presents a good nomogram that can aid pre-biopsy risk stratification for the detection of csPCa, and that may help inform biopsy decisions in patients with negative MRI results.

The prevalence and risk factors for depressive symptoms in frontline nurses under COVID-19 pandemic based on a large cross-sectional study using the propensity score-matched method.

INTRODUCTION: To explore the prevalence of depressive symptoms and the associated risk factors in frontline nurses under COVID-19 pandemic. METHODS: This cross-sectional study was conducted from February 20, 2020 to March 20, 2020 and involved 562 frontline nurses. The effective response rate was 87.68%. After propensity score matched, there were 498 participants left. Extensive characteristics, including demographics, dietary habits, life-related factors, work-related factors, and psychological factors were collected based on a self-reported questionnaire. Specific scales measured the levels of sleep quality, physical activity, depressive symptoms, perceived organization support and psychological capital. Adjusted odds ratios and 95% confidence intervals were determined by binary paired logistic regression. RESULTS: Of the nurses enrolled in the study, 50.90% had depressive symptoms. Three independent risk factors were identified: poor sleep quality (OR = 1.608, 95% CI: 1.384-1.896), lower optimism of psychological capital (OR = 0.879, 95% CI: 0.805-0.960) and no visiting friend constantly (OR = 0.513, 95% CI: 0.286-0.920). CONCLUSIONS: This study revealed a considerable high prevalence of depressive symptoms in frontline nurses during the COVID-19 outbreak, and identified three risk factors, which were poor sleep quality, lower optimism of psychological capital, and no visiting friend constantly. Protecting mental health of nurses is important for COVID-19 pandemic control and their wellbeing. These findings enrich the existing theoretical model of depression and demonstrated a critical need for additional strategies that could address the mental health in frontline nurses for policymakers.

Risk factors and oncological outcomes of urethral recurrence in male patients with muscle invasive bladder cancer after radical cystectomy combined with urinary diversion: a propensity score-matched case control study.

BACKGROUND: Radical cystectomy (RC) is the primary treatment strategy for muscle invasive bladder cancer (MIBC). However, it carries a high risk of urethral recurrence (UR) in male patients. The risk factors and oncological outcomes of UR remain unclear. We aimed to identify the risk factors and oncological outcomes of UR in male patients with MIBC after RC combined with urinary diversion. METHODS: After propensity score matching, we evaluated 137 male patients with MIBC who underwent RC combined with urinary diversion at our center between January 1, 2007 and December 31, 2015. Patient demographics, comorbidity, and perioperative data were recorded. Univariate and multivariate Cox proportional hazards regression were used to estimate the hazard ratio and 95% confidence intervals. Cancer-specific survival (CSS) and overall survival (OS) were measured using the Kaplan-Meier curve with log-rank test. P < 0.05 was considered statistically significant. RESULTS: Of the 310 patients, 30 (9.7%) patients underwent UR. In the matched group, the independent risk factors of UR were history of TURB (HR = 3.069, P = 0.018), tumor stage (T3 vs. T2, HR = 3.997, P = 0.014; T4 vs. T2, HR = 2.962, P = 0.015), and tumor multifocality (HR = 2.854, P = 0.011). The CSS and OS of patients with UR were equivalent to the patients without UR (P = 0.295, P = 0.616). CONCLUSION: This propensity score-matched case-control study showed that UR is not rare in male patients with MIBC after RC combined with urinary diversion. We identified three independent risk factors of UR: history of TURB, tumor stage, and tumor mutifocality. The oncological outcomes were equivalent between patients with and without UR. These findings could help improve treatment strategies and follow-up schedules.

Development and validation of a clinical model to predict intraoperative hemodynamic instability in patients with pheochromocytomas surgery.

Although currently the primary strategy for the treatment of pheochromocytomas is surgery, it is associated with a high risk of intraoperative hemodynamic instability (IHD), even with adequate preoperative medical preparation, which may result in life-threatening situations. The aim of this study was to develop and validate a nomogram for preoperative prediction of IHD related to pheochromocytoma surgery. The development cohort consisted of 283 patients with pheochromocytoma who underwent unilateral laparoscopic or open adrenaletomy at our center between January 1, 2007 and December 31, 2016. The clinicopathological characteristics of each patient were recorded. The least absolute shrinkage and selection operator binary logistic regression model was used for data dimension reduction and feature selection, while multivariable logistic regression analysis was used to develop the prediction model. An independent cohort consisting of 119 consecutive patients from January 1, 2017 to December 31, 2018 was used for validation. The performance of the prediction model was assessed in regards to discrimination, calibration, and clinical usefulness. The predictors of this model included body mass index, coronary heart disease, tumor size, and preoperative use of crystal/colloid fluid. For the validation cohort, the model showed good discrimination with an area under the receiver operating characteristic of 0.767 (95% CI, 0.667-0.857) and good calibration (unreliability test, p = 0.852; Hosmer-Lemeshow test, p = 0.9309). Decision curve analysis demonstrated that the model was clinically useful. This nomogram to facilitate preoperative individualized prediction of IHD in patients with pheochromocytoma may help to improve the perioperative strategy and treatment outcome.

Development and validation of a predictive model for predicting cardiovascular morbidity in patients after pheochromocytoma surgery.

OBJECTIVE: Although surgical resection is the primary treatment method for pheochromocytoma, it carries a high risk of morbidity, especially cardiovascular-related morbidity. There are no models for predicting cardiovascular morbidity after pheochromocytoma surgery. Thus, we developed and validated a model for the preoperative prediction of cardiovascular morbidity after pheochromocytoma surgery. DESIGN: The development cohort consisted of 262 patients who underwent unilateral laparoscopic or open pheochromocytoma surgery at our centre between 1 January 2007 and 31 December 2016. Patient's clinicopathologic data were recorded. The LASSO regression was used for data dimension reduction and feature selection; then, multivariable logistic regression analysis was used to develop the prediction model. An independent cohort consisting of 112 consecutive patients from 1 January 2017 and 31 December 2018 was used for validation. The performance of this prediction model was assessed with respect to discrimination, calibration and clinical usefulness. RESULTS: The predictors in this prediction model included body mass index, history of coronary heart disease, tumour size, intraoperative hemodynamic instability and use of crystal/colloid fluids preoperatively. In the validation cohort, the model showed good discrimination with an AUROC of 0.869 (95% CI, 0.797, 0.940) and good calibration (unreliability test, P = .852). Decision curve analysis demonstrated that the model was also clinically useful. CONCLUSION: This study presented a good nomogram that could facilitate the preoperative individualized prediction of cardiovascular morbidity after pheochromocytoma surgery, which may help improve perioperative strategy and good treatment outcomes.

Risk factors for postoperative cardiovascular morbidity after pheochromocytoma surgery: a large single center retrospective analysis.

Surgical resection is the primary treatment strategy for pheochromocytoma; however, it carries a high risk of morbidity and mortality, especially with respect to cardiovascular complications, which is the most common kinds of morbidity. The risk factors for morbidity remain unclear and require further exploration, moreover no studies focus on risk factors for cardiovascular morbidity. Herein we identified the risk factors for cardiovascular morbidity after pheochromocytoma surgery in Chinese patients. We retrospectively reviewed 262 patients who underwent unilateral surgical resection of pheochromocytoma at our center between 1 January 2007 and 31 December 2016. Patient demographics and extensive perioperative data were recorded and evaluated. Adjusted odds ratios and 95% confidence intervals were determined by multivariate logistic regression. Cut-off values and the area under the curve for continuous risk factors were calculated based on receiver operating characteristic curve analysis. A p-value <0.05 was considered statistically significant. Of the 262 patients, 63 (24.0%) had cardiovascular morbidity. The independent risk factors for cardiovascular morbidity were low body mass index, large radiographic tumor size, coronary heart disease, no preoperative crystal/colloid administration, and intraoperative hemodynamic instability; the corresponding odds ratio were 0.762 (p < 0.001), 1.208 (p = 0.010), 2.378 (p = 0.012), 2.720 (p = 0.011), and 4.764 (p = 0.001), respectively. The optimal cut-off values for body mass index and radiographic tumor size were 24.59 kg/m2 and 6.05 cm. We found that cardiovascular morbidity is common in patients after pheochromocytoma surgery. We identified five independent risk factors for cardiovascular morbidity. Identification of these risk factors may help to improve treatment strategies.

Effectiveness of a modified doctor-patient communication training Programme designed for surgical residents in China: a prospective, large-volume study at a single Centre.

BACKGROUND: Effective doctor-patient communication (DPC) is important to improve the quality of care and treatment outcomes. This study aimed to evaluate the effectiveness of a modified DPC training programme designed for surgical residents in China. METHODS: A total of 210 surgical residents from 7 specialties were recruited to participate in a communication skills training programme. The extended SEGUE scale was administered to supervisors, and a visual analogue scale (VAS) was administered to standardized patients (SPs) and trainees. Evaluations were conducted by comparing the pre-post scale scores (before, immediately after and 1 month after the programme). Training effects were assessed using the Friedman test and the intraclass correlation coefficient (ICC). RESULTS: Compared to the extended SEGUE scale total scores before the programme, the scores both immediately after and 1 month after the program increased significantly (15.88 ± 1.93 vs. 26.40 ± 1.47 and 26.15 ± 1.36, respectively, p < 0.001). The scores of five of the six dimensions in the extended SEGUE scale significantly increased (p < 0.001), except for the patient's perspective dimension score, which had no change (p = 0.162). With respect to this dimension, a subgroup analysis by gender indicated an increase among females (p < 0.001) and a decrease among males (p < 0.001). The VAS scores, which were evaluated for the SPs and trainees, increased significantly compared to the scores before the program, both immediately after and 1 month after the programme (4.31 ± 1.35 vs. 7.36 ± 1.62 and 7.34 ± 1.24, p < 0.001; 7.31 ± 1.25 vs. 8.39 ± 1.32 and 8.30 ± 1.24, p < 0.001, respectively). The consistency of the VAS between the SPs and surgical residents was 0.26 (p < 0.001), 0.70 (p < 0.001), and 0.70 (p < 0.001) before, immediately after and 1 month after the programme, respectively. CONCLUSION: This training programme improved the DPC competency of surgical residents, effectively increased the levels of satisfaction of both SPs and surgical residents, and improved the consistency of evaluation between SPs and surgical residents during doctor-patient encounters. The registration UIN is ChiCTR1800019790 from November 28, 2018.

Prognosis and biological function of SGOL1 in clear cell renal cell carcinoma: a multiomics analysis.

BACKGROUND: Shugoshin-1 (SGOL1) is a mammalian ortholog of Shugoshin in yeast and is essential for precise chromosome segregation during mitosis and meiosis. Aberrant SGOL1 expression was reported to be closely correlated with the malignant progression of various tumors. However, the expression pattern and biological function of SGOL1 in clear cell renal cell carcinoma (ccRCC) are unclear. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provide mRNA expression data and outcome information for ccRCC patients. Immunohistochemistry (IHC) of ccRCC tissue chips verified SGOL1 protein expression in ccRCC patients. Data processing and visualization were performed with the UALCAN, TISIDB, TIMER, GSCA, LinkedOmics, and starBase databases. Gene Ontology (GO) annotation and gene set enrichment analysis (GSEA) were used to identify SGOL1-related biological functions and signaling pathways. Immune infiltration analysis was performed using the TISIDB database, ssGSEA algorithm, and TCGA-KIRC cohort. The biological role of SGOL1 in ccRCC was investigated using a series of in vitro cytological assays, including the MTT assay, EdU staining assay, flow cytometry analysis, Transwell assay, and wound healing assay. RESULTS: SGOL1 was highly expressed in ccRCC and linked to adverse clinicopathological parameters and unfavorable prognosis. Multivariate logistic regression and nomogram calibration suggested that SGOL1 might serve as an independent and reliable prognostic predictor of ccRCC. Functional enrichment analysis indicated that SGOL1 may be involved in the cell cycle, the p53 pathway, DNA replication, and T-cell activation. Furthermore, tumor microenvironment (TME) analysis suggested that SGOL1 was positively associated with Treg infiltration and immune checkpoint upregulation. In addition, we identified a potential SNHG17/PVT1/ZMIZ1-AS1-miR-23b-3p-SGOL1 axis correlated with ccRCC carcinogenesis and progression. Finally, we demonstrated that SGOL1 promoted ccRCC cell proliferation, migratory capacity, and invasion in vitro. CONCLUSIONS: SGOL1 potentially functions as an oncogene in ccRCC progression and might contribute to the immunosuppressive TME by increasing Treg infiltration and checkpoint expression, suggesting that targeting SGOL1 could be a novel therapeutic strategy for the treatment of ccRCC patients.

Impact of cascade reservoirs on nutrients transported downstream and regulation method based on hydraulic retention time.

Cascade reservoirs construction has modified the nutrients dynamics and biogeochemical cycles, consequently affecting the composition and productivity of river ecosystems. The Jinsha River, as the predominant contributor to runoff, suspended sediment (SS), and nutrients production within the Yangtze River, is a typical cascade reservoir region with unclear transport patterns and retention mechanisms of nutrients (nitrogen and phosphorus). Furthermore, how to regulate nutrients delivery in the cascade reservoirs region is also an urgent issue for basin water environment study. Therefore, we monitored monthly variations in nitrogen and phosphorus concentrations from November 2021 to October 2022 in the cascade reservoirs of the Jinsha River. The results indicated that the concentrations and fluxes of total phosphorus (TP) and particulate phosphorus (PP) decreased along the cascade of reservoirs, primarily due to PP deposited with SS, while opposing trends for total nitrogen (TN) and dissolved total nitrogen (DTN), which might be the consequences of human inputs and the increase of dissolved inorganic nitrogen discharged from the bottom of the reservoirs. Moreover, the positive average annual retention ratios for TP and PP were 10% and 16%, respectively, in contrast to the negative averages of -8 % for TN and -11% for particulate nitrogen (PN). The variability in runoff-sediment and hydraulic retention time (HRT) of cascade reservoirs played crucial roles in the retention of TP and PP. A regulatory threshold of HRT = 5.3 days in the flood season was obtained for controlling the balance of TP based on the stronger relationship between HRT and TP retention ratio. Consequently, the HRT of these reservoirs could be managed to control nutrients delivery, which was of particular significance for basin government institutions. This study enhances our comprehension of how cascade reservoirs influence the distribution and transport patterns of nutrients, offering a fresh perspective on nutrients delivery regulation.

NEIL3 promotes cell proliferation of ccRCC via the cyclin D1-Rb-E2F1 feedback loop regulation.

Nei endonuclease VIII-like 3 (NEIL3), a novel tumor-related gene, is differentially expressed and involved in pathophysiological processes in multiple tumors. However, the potential biological functions and molecular mechanisms of NEIL3 in human clear cell renal cell carcinoma (ccRCC) have not been identified. In this research, we demonstrated that NEIL3, transcriptionally activated by E2F1, served as an oncogene to facilitate cell proliferation and cell cycle progression and contribute to tumorigenesis via the cyclin D1-Rb-E2F1 feedback loop in ccRCC. First, we found that NEIL3 expression was upregulated in ccRCC tissues and cell lines compared with matched adjacent nontumor tissues and renal tubular epithelial cells and was also positively correlated with adverse clinicopathological characteristics, such as advanced cancer stages and higher tumor grades, and acted as an independent prognostic marker in ccRCC. Mechanistically, we demonstrated that NEIL3 promoted cell proliferation, DNA replication and cell cycle progression in vitro and tumor growth in vivo. Furthermore, we found that NEIL3 overexpression activated the cyclin D1-Rb-E2F1 pathway, and the E2F1 upregulation transcriptionally activated NEIL3 expression, thus forming a feedback loop. In addition, there was a positive correlation between NEIL3 and E2F1 expression in clinical specimens of ccRCC. Taken together, our results suggest that NEIL3 serves as a proto-oncogene in ccRCC and presents as a novel candidate for ccRCC diagnosis and treatment.

A novel framework for investigating the mechanisms of climate change and anthropogenic activities on the evolution of hydrological drought.

Climate change and anthropogenic activity are the primary drivers of water cycle changes. Hydrological droughts are caused by a shortage of surface and/or groundwater resources caused by climate change and/or anthropogenic activity. Existing hydrological models have primarily focused on simulating natural water cycle processes, while limited research has investigated the influence of anthropogenic activities on water cycle processes. This study proposes a novel framework that integrates a distributed hydrological model and an attribution analysis method to assess the impacts of climate change and anthropogenic activities on hydrological drought The distributed dualistic water cycle model was applied to the Fuhe River Basin (FRB), and it generated a Nash-Sutcliffe efficiency coefficient > 0.85 with a relative error of <5 %. Excluding the year with extreme drought conditions, our analysis revealed that climate change negatively impacted the average drought duration (-105.5 %) and intensity (-23.6 %) because of increasing precipitation. However, anthropogenic activities continued to contribute positively to the drought, accounting for 5.5 % and 123.6 % of the average drought duration and intensity, respectively, because of increased water consumption. When accounting for extreme drought years, our results suggested that climate change has contributed negatively to the average duration of drought (-113.2 %) but positively to its intensity (7.8 %). Further, we found that anthropogenic activities contributed positively to both the average drought duration and intensity (13.2 % and 92.2 %, respectively). While climate change can potentially mitigate hydrological drought in the FRB by boosting precipitation levels, its overall effect may exacerbate drought through the amplification of extreme climate events resulting from global climate change. Therefore, greater attention should be paid to the effects of extreme drought.

Inhibition of autophagy can promote the apoptosis of bladder cancer cells induced by SC66 through the endoplasmic reticulum stress pathway.

Bladder cancer is among the ten most prevalent cancer types worldwide, and its prognosis has not improved significantly in the past three decades because of cognitive limitations in the molecular mechanisms that drive the malignant progression of bladder cancer. Therefore, there is an urgent need to identify new therapeutic drugs or molecular targets to improve the prognosis of patients with bladder cancer. SC66, a novel allosteric inhibitor of AKT, has recently been reported to exert potent anticancer effects on various cancer cells. However, the mechanisms underlying its anticancer effects in bladder cancer remain largely unknown. Consequently, this study aimed to conduct a series of molecular and cellular biology experiments to verify the anticancer effect and potential mechanism of action of SC66 in bladder cancer in vitro. A xenograft tumor model was established to confirm its anticancer role in vivo. Our results showed that SC66 inhibited cell proliferation, triggered mitochondria-mediated apoptosis, and initiated autophagy in bladder cancer cells dose-dependently. In addition, our results suggested that SC66-caused apoptosis and autophagy were endoplasmic reticulum stress-dependent. Interestingly, the activation of autophagy can partially protect bladder cancer cells from apoptosis under endoplasmic reticulum stress induced by SC66 treatment. This study shows that SC66 exerts its anticancer impact on bladder cancer by inhibiting cell proliferation and inducing apoptosis. It also reveals that inhibiting autophagy can increase the cytotoxic effects of SC66 in bladder cancer. Overall, this is the first study on the anticancer effect of SC66 mediated by the endoplasmic reticulum stress pathway and the first report on the AKT-independent anticancer mechanism of SC66 in bladder cancer. Conclusively, exploring the relationship between apoptosis, autophagy, and endoplasmic reticulum stress induced by SC66 indicates that SC66 is a promising novel agent for patients with bladder cancer.

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer. METHODS: Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein-protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole. RESULTS: Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways. CONCLUSIONS: We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer. SUBJECTS: Bioinformatics, Computational Biology, Molecular Biology.

Adsorption of microplastics on aquifer media: Effects of the action time, initial concentration, ionic strength, ionic types and dissolved organic matter.

The adsorption of microplastic (MPs) on aquifer media is affected by their own properties and environmental factors. Research results have shown that the adsorption capacity of MPs on the three media has the following order: fine sand > medium sand > coarse sand, and the adsorption equilibrium times are 8 h, 12 h and 24 h, respectively. The adsorption process has three stages (fast linear distribution, slow adsorption and equilibrium stability), and the action law is compounded by the pseudo-second-order kinetic equation. After adsorption, MPs were observed on the three media, and there were single existence and aggregation phenomena. The energy spectrum analysis indicates that elemental carbon (C) appears on the surface of the medium after the action occurs, and the surface of the media adsorbs MPs to varying degrees. According to the results of infrared spectroscopy, after action, the peak areas of the absorption peaks at 680-880 cm-1 and 1450-1620 cm-1 increase. The absorption peaks are mainly C-H out-of-plane bending vibrations from aromatic hydrocarbons and C-H stretching vibrations on the benzene ring skeleton. As the initial concentration increases, the equilibrium adsorption capacity increases linearly. The isothermal adsorption of MPs in porous media conforms to the Freundlich model. The adsorption process is also affected by different anions and cations. The higher the ionic strength of NH4+ is, the weaker the electrostatic effect of negatively charged MPs, thereby increasing the adsorption capacity of microplastics on porous media. Ca2+ can promote the adsorption of MPs by the media through the formation of ternary complexes between cations, MPs and surface functional groups. The increase in SO42- and HCO3- concentrations gradually inhibits the adsorption of MPs.

[Risk Assessment Method of Non-point Source Pollution Output for Watershed Using High Resolution Data].

In recent years, non-point source pollution has become the main cause of water quality deterioration in some reservoirs in China. Taking the Panjiakou Reservoir as an example, the classical output risk model was improved by introducing a precipitation factor and terrain factor. Combined with high-resolution satellite precipitation products (GPM) and GF-6 satellite images, a high-resolution data-driven risk assessment method for non-point source pollution output was established to study the temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin. The results showed that the non-point source pollution output risk was high in the study area in 2018. The areas with higher and highest risk of nitrogen pollution output accounted for approximately 70.6% of the total watershed area, whereas the higher risk of phosphorus pollution output accounted for approximately 21.9%. The temporal and spatial distribution characteristics of non-point source pollution output risk in the Panjiakou Reservoir basin were analyzed. It was found that the non-point source pollution output risk in the Panjiakou Reservoir basin increased first and then decreased from April to September. This was consistent with the spatial and temporal distribution of precipitation in the basin. Combined with the analysis of land use distribution characteristics, the upstream area of the basin was mainly cultivated land, whereas cities were concentrated in the downstream portion of the basin. Affected by agricultural production and human activities, the risk of non-point source pollution output was higher in these regions. In view of the temporal and spatial distribution characteristics of non-point source pollution output risk, it is necessary to formulate a reasonable agricultural fertilization method, plan the landscape layout of source-sinks, and construct vegetation buffer zones.

Identification of a six-gene prognostic signature for bladder cancer associated macrophage.

As major components of the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play an exceedingly complicated role in tumor progression and tumorigenesis. However, few studies have reported the specific TAM gene signature in bladder cancer. Herein, this study focused on developing a TAM-related prognostic model in bladder cancer patients based on The Cancer Genome Atlas (TCGA) data. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key genes related to TAM (M2 macrophage). Gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed the functional categories of the key genes. Simultaneously, we used the Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regressions to establish a TMA-related prognostic model containing six key genes: TBXAS1, GYPC, HPGDS, GAB3, ADORA3, and FOLR2. Subsequently, single-cell sequencing data downloaded from Gene Expression Omnibus (GEO) suggested that the six genes in the prognostic model were expressed in TAM specifically and may be involved in TAM polarization. In summary, our research uncovered six-TAM related genes that may have an effect on risk stratification in bladder cancer patients and could be regarded as potential TAM-related biomarkers.

Transurethral endoscopic extensive incision of complex urethral diverticula in symptomatic women: case series in a single center experience with long-term follow-up.

BACKGROUND: Urethral diverticula (UD) affect 1-6% of adult women. Complex UD are rare, but can be challenging to manage. To evaluate the efficacy and safety of transurethral endoscopic extensive incision of complex UD in symptomatic women. MATERIALS AND METHODS: We retrospectively evaluated 22 female patients with complex UD who underwent transurethral endoscopic extensive incision management in our hospital. This technique was completed by one experienced surgeon over a 7-year period between August 2012 and July 2019. The surgical technique involved placing the patient in a lithotomy position, inserting the needle electrode endoscopically, and incising the tented roof of the UD from its orifice until the entire roof had been opened widely. Outcome data included complete symptom resolution rate, imaging data, de novo stress urinary incontinence (SUI), recurrence, short-term and long-term complications. Cure was defined as decreased UD volume on postoperative magnetic resonance imaging and no post-voiding urinary retention in the diverticular cavity, with symptom resolution. RESULTS: The initial symptom-resolution rate after 37.0 (27.0, 50.0) months' follow-up was 81.80% (18/22) and the de novo SUI rate was 13.60% (3/22). No patients required additional operations after conservative therapy. There was no symptomatic or imaging recurrence, and no short-term complications. CONCLUSION: Transurethral endoscopic extensive incision was an effective and safe treatment for symptomatic female complex UD. Its symptom-resolution rate and de novo SUI rate might be superior to the conventional transvaginal approach. Moreover, it was less invasive and easier to conduct, with fewer complications.