High-Performance All-Small-Molecule Organic Solar Cells Fabricated via Halogen-Free Preparation Process.

Small-molecule organic photovoltaic materials attract more attention attributing to their precisely defined structure, ease of synthesis, and reduced batch-to-batch variations. The majority of all-small-molecule organic solar cells (ASM-OSCs) have traditionally relied on halogenated solvents for dissolving photovoltaic materials as well as used for the additives or solvent vapor annealing. However, these halogen-based processes pose risks to the environment and human health, potentially impeding future commercial production. Herein, we conducted an investigation into the impact of various nonhalogen solvents on the performance of the devices. By selecting the high boiling point solvent toluene, we achieved a desirable phase separation and stable morphology characterized by fibrous crystals within the blend film. Consequently, the power conversion efficiencies of 14.4 and 11.7% were obtained from H31:Y6-based small-area (0.04 cm2) and large-area (1 cm2) devices with steady performance, respectively. This study successfully demonstrated the fabrication of ASM-OSCs without employing halogenated solvent processes, thus offering promising prospects for the commercial production of ASM-OSCs.

Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

MicroRNA-367-3p directly targets RAB23 and inhibits proliferation, migration and invasion of bladder cancer cells and increases cisplatin sensitivity.

OBJECTIVES: This study investigated the biological role of miR-367-3p upregulation in bladder cancer and verified the mutual relation between miR-367-3p and RAB23. MATERIALS AND METHODS: Expression levels of miR-367-3p were determined by RT-qPCR in bladder cancer cell lines and human bladder cancer tissues. The effects of miR-367-3p on proliferation, migration and invasion were evaluated by cell colony formation assays, wound healing assays and trans-well assays, respectively. The effects of miR-367-3p and RAB23 on cisplatin sensitivity of bladder cancer cells were assessed by CCK-8 assay. The expression of its target-RAB23 was determined by western blotting in T24, 5637. Plasmids used in dual-luciferase assays were constructed to confirm the action of miR-367-3p on downstream target-RAB23 in T24 cells. And also, the role of miR-367-3p in tumorigenesis was also confirmed in nude mouse models. RESULTS: The downregulation of miR-367-3p was observed in human bladder cancer tissues. MiR-367-3p downregulation positively correlated with tumor stage and tumor grade. MiR-367-3p overexpression in T24, 5637 cells suppressed the proliferation, migration, and invasion of bladder cancer cells in vitro while decreasing IC50 values under T24 and 5637 cisplatin treatment conditions. RAB23 was shown to be upregulated in bladder cancer tissues and cell lines. MiR-367-3p directly bound to the 3' UTR of RAB23 in T24 cells. RAB23 was potentially accounted for the aforementioned functions of miR-367-3p. Tumor formation experiments in nude mouse models confirmed that overexpression of miR-367-3p could inhibit tumor growth and invasion in vivo. CONCLUSIONS: miR-367-3p acts as a tumor suppressor in bladder cancer by downregulating RAB23 signaling. We conjecture that miR-367-3p-mediated downregulation of RAB23 expression may be a new therapeutic strategy for bladder cancer treatment.

Development and validation of a nomogram for predicting osteoporosis in prostate cancer patients: A cross-sectional study from China.

BACKGROUND: The specific risk factors contributing to the development of osteoporosis and the appropriate timing of treatment in Chinese prostate cancer (PCa) patients remain unclear. Our objective was to develop and validate a nomogram capable of predicting the occurrence of osteoporosis in PCa patients. METHODS: We conducted a cross-sectional study with PCa patients attending the Second Hospital of Tianjin Medical University, collecting data from June 2021 to February 2023. The patients were divided into training and validation sets in a 7:3 ratio. The LASSO regression was used to identify the most relevant predictive variables, and the multivariable logistic regression was used to construct the nomogram. The nomogram's performance was validated through receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA) in both the training and validation sets. RESULTS: We collected data from a total of 596 patients and then constructed the nomogram using age, body mass index, hemoglobin, vitamin D3, testosterone, and androgen deprivation therapy duration. The C-index of the nomogram was 0.923 in the training set and 0.859 in the validation set. The nomogram showed good consistency in both sets. DCA demonstrated the clinical benefit of the nomogram across various prediction thresholds. Furthermore, a separate nomogram was constructed to predict bone loss in patients undergoing ADT, exhibiting equally favorable diagnostic performance and clinical benefit. CONCLUSION: This study constructed two reliable nomograms to predict osteoporosis and bone loss, integrating personal health information and PCa-specific treatment data. These nomograms offer an easy and individualized approach to predict the occurrence of osteoporosis and bone loss in PCa patients.

Comprehensive analysis of predictive factors for upstaging in intraprostatic cancer after radical prostatectomy: Different patterns of spread exist in lesions at different locations.

BACKGROUND: Accurate assessment of the clinical staging is crucial for determining the need for radical prostatectomy (RP) in prostate cancer (PCa). However, the current methods for PCa staging may yield incorrect results. This study aimed to comprehensively analyze independent predictors of postoperative upstaging of intraprostatic cancer. METHODS: We conducted a retrospective analysis of data from intraprostatic cancer patients who underwent radical surgery between March 2019 and December 2022. Intraprostatic cancer was defined as a lesion confined to the prostate, excluding cases where multiparameter magnetic resonance imaging (mpMRI) showed the lesion in contact with the prostatic capsule. We assessed independent predictors of extraprostatic extension (EPE) and analyzed their association with positive surgical margin (PSM) status. In addition, based on the distance of the lesion from the capsule on mpMRI, we divided the patients into non-transition zone and transition zone groups for further analysis. RESULTS: A total of 500 patients were included in our study. Logistic regression analysis revealed that biopsy Gleason grade group (GG) (odds ratio, OR: 1.370, 95% confidence interval, CI: 1.093-1.718) and perineural invasion (PNI) (OR: 2.746, 95% CI: 1.420-5.309) were predictive factors for postoperative EPE. Both biopsy GG and PNI were associated with lateral (GG: OR: 1.270, 95% CI: 1.074-1.501; PNI: OR: 2.733, 95% CI: 1.521-4.911) and basal (GG: OR: 1.491, 95% CI: 1.194-1.862; PNI: OR: 3.730, 95% CI: 1.929-7.214) PSM but not with apex PSM (GG: OR: 1.176, 95% CI: 0.989-1.399; PNI: OR: 1.204, 95% CI: 0.609-2.381) after RP. Finally, PNI was an independent predictor of EPE in the transition zone (OR: 11.235, 95% CI: 2.779-45.428) but not in the non-transition zone (OR: 1.942, 95% CI: 0.920-4.098). CONCLUSION: PNI and higher GG may indicate upstaging of tumors in patients with intraprostatic carcinoma. These two factors are associated with PSM in locations other than the apex of the prostate. Importantly, cancer in the transition zone of the prostate is more likely to spread externally through nerve invasion than cancer in the non-transition zone.

Secretion of IL-6 and IL-8 in the senescence of bone marrow mesenchymal stem cells is regulated by autophagy via FoxO3a.

Bone marrow mesenchymal stem cells (BMSCs) are widely used for therapeutic applications in tissue engineering and regenerative medicine. Nevertheless, the function of BMSCs is adversely affected by senescence. Thus, understanding the molecular mechanisms that contribute to BMSC senescence is critical for the development of BMSC-based tissue engineering and regenerative medicine. In this study, senescent BMSCs were characterized with >80 % of BMSCs stained positive for SA-ß-gal, increased expressions of senescence-related genes (p16INK4a and p21Waf1). These senescent characters were accompanied by elevated autophagic activity, up-regulation of interleukin 6 (IL-6), IL-8, and FoxO3a. Autophagic activity inhibition alleviated the senescent state with reduced levels of IL-6 and IL-8 during BMSC senescence. The enhanced autophagic activity upregulated the levels of IL-6 and IL-8 which is associated with up-regulation of FoxO3a, and knockdown of FoxO3a reduced IL-6 and IL-8 expression in senescent BMSCs. Therefore, this study indicated the pivotal role of autophagic activity in the expressions of IL-6 and IL-8 during BMSC senescence, which is regulated by FoxO3a.

Analysis of risk factors for Gleason score upgrading after radical prostatectomy in a Chinese cohort.

BACKGROUND: To study the risk factors of Gleason score upgrading (GSU) after radical prostatectomy (RP) in a Chinese cohort. METHODS: The data of 637 patients who underwent prostate biopsy and RP in our hospital from January 2014 to January 2021 were retrospectively analyzed. The age, body mass index (BMI), prostate-specific antigen (PSA) level, testosterone (TT) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), aspartate aminotransferase/alanine transaminase (AST/ALT) ratio, clinical stage, the biopsy method, and pathological characteristics of specimens after biopsy and RP were collected for all patients. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors of GSU after RP. The predictive efficacy was verified with the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. We performed the analysis separately in the overall cohort and in the cohort with Gleason score (GS) = 6. RESULTS: In the overall cohort, 177 patients (27.79%) had GSU, and in the GS = 6 cohort, 68 patients (60.18%) had GSU. Multivariate logistic regression analysis showed that in the overall cohort, clinical stage ≥T2c (OR = 3.201, p < 0.001), the number of positive cores ≥3 (OR = 0.435, p = 0.04), and positive rate of biopsy (OR = 0.990, p = 0.016) can affect whether GS is upgraded, and the AUC of the combination of the three indicators for predicting the occurrence of GSU was 0.627. In the GS = 6 cohort, multivariate logistic regression analysis showed that clinical stage ≥T2c (OR = 4.690, p = 0.001) was a risk factor for GSU, and the AUC predicted to occur GSU is 0.675. CONCLUSION: Clinical stage ≥T2c, the number of positive cores <3, and lower positive rate of biopsy are the risk factors of GSU. This study may provide some references for clinicians to judge the accuracy of biopsy pathological grading and formulate treatment strategies, but the specific effect still needs clinical practice certification.

A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts in understanding the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) was involved in the development of varied tumors. However, a comprehensive analysis of the prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA-sequencing expression data is still limited. METHODS: RNA-sequencing expression data were taken out from GTEx database and TCGA database, a total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained by WGCNA and differential expression analysis. Following, the communication of mRNAs and lncRNAs with targeted miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was further constructed by univariate Cox regression, Lasso methods, and multivariate Cox regression analysis. RESULTS: A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dysregulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature including eight genes based on this ceRNA was determined followed by the development of a nomogram predicting 1-, 3-, and 5-year survival probability for ccRCC. CONCLUSION: It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

The association between sleep duration and prostate cancer: A systematic review and meta-analysis.

The association between sleep duration and prostate cancer (PCa) risk is still unclear. We performed a systematic review and meta-analysis to explore if sleep duration is associated with PCa in men.A comprehensive literature search was conducted in November 2019 based on the Pubmed, Embase, and Cochrane databases. After extracting the data, the random effects model was used to calculate the pooled Risk Ratio (RR) and it's 95% confidence interval (CI) to represent the correlation between sleep duration and PCa risk.Overall, we included 6 studies in our meta-analysis. Our pooled results showed that neither short sleep (RR = 0.99; 95%CI:0.91-1.07, P = .74) nor long sleep (RR = 0.88; 95%CI:0.75-1.04, P = .15) was associated with the risk of PCa.Sleep duration has no significant effect on PCa risk. Long sleep may have a potential protective effect on PCa incidence.

Identification and Validation of a Novel Clinical Signature to Predict the Prognosis in Confirmed Coronavirus Disease 2019 Patients.

BACKGROUND: Our aim in this study was to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of coronavirus disease 2019 (COVID-19), which has caused a worldwide pandemic. METHODS: COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. The disease prognosis signature of COVID-19 was validated in the test group. RESULTS: The signature of COVID-19 was combined with the following 5 indicators: neutrophil count, lymphocyte count, procalcitonin, age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P < .001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test, P < .001). The area under the receiver operating characteristic (ROC) curve showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the 5 indicators alone. CONCLUSIONS: The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.

The role of Snf5 in the osteogenic differentiation potential during replicative senescence of rat mesenchymal stromal cells.

The osteogenic capacities of bone marrow-derived stromal cells (BMSCs) diminish during replicative senescence, and these changes affect the success of therapeutic application of BMSCs. In this study, we sought to explore the molecular mechanisms underlying the osteogenic differentiation capacities that occur during replicative senescence. It is well known that Oct4 is a key transcription factor essential for maintaining differentiation capacities of the stem cells. In this study, we found that BMSCs at passage 6 (replicative senescent BMSCs) showed marked decreases in the osteogenic differentiation potential and the level of Oct4. These were accompanied by reduced levels of Snf5 and histone H3 lysine-4 trimethylation (H3K4me3) in the Oct4 promoter. In BMSCs at passage 2, knockdown of Snf5 diminished expression of Oct4 and disrupted the up-regulation of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) after osteogenic differentiation induction, which was accompanied by a reduction in Snf5 and H3K4me3 binding to the Oct4 promoter. These findings indicate that the decreased level of Snf5 binding to the promoter region of the Oct4 gene down-regulated the expression of Oct4, which may be the mechanism underlying the decline in osteogenic capacities in replicative senescent BMSCs.

A Bis(methylpiperazinylstyryl)phenanthroline as a Fluorescent Ligand for G-Quadruplexes.

G-quadruplex (G4)-forming sequences are prevalent in the genome and are considered to play important roles in gene regulation, and hence have been viewed as potential therapeutic targets in oncology. However, the structures and functions of most G4s in the genome are poorly understood. Therefore, the development of fluorescent probes and ligands for G4s is important for G4 research and drug discovery. Herein, we report a new G4 ligand, 2,9-bis[4-(4-methylpiperazin-1-yl)styryl]-1,10-phenanthroline (BMSP), which was synthesized by a simple process. BMSP exhibits almost no fluorescence in aqueous buffer. The interaction of BMSP with G4s greatly enhances its fluorescence with a large Stokes' shift of 160 nm. Antiparallel human telomeric G4s exhibit the strongest binding affinity (Kd ≈0.13 µm) to BMSP and induce a fluorescence enhancement of up to 150-fold. BMSP binds to G4s through π-π stacking on the terminal G-quartets. BMSP can enter live cells, and it strongly inhibits the growth of cancer cells rather than causing cell death. Our results suggest that BMSP has the potential to serve both as a fluorescent probe for some G4s and as a chemotherapeutic agent for cancer treatment.