Chemoselective C-H Hydroxylation and Borylation of N-Phenylbenzamides using BBr3.

A novel metal-free chemoselective C-H hydroxylation and borylation of N-phenylbenzamides using BBr3 is described. The protocol generates the corresponding phenols and arylboronic esters in moderate to excellent yields under mild conditions with brilliant chemoselectivity. Additionally, this strategy can be realized in one pot, and several potential bioactive derivatives can be synthesized efficiently. Density functional theory calculations certify that the preferred pathway for this metal-free C-H hydroxylation process is the formation of a five-membered boracycle.

Diagnostic value of random urine protein/creatinine ratio for preeclampsia.

Objective: The 24-h urine protein remains the gold standard to diagnose proteinuria in suspected preeclamptic patients. However, this test is time consuming and sometimes inaccurate. In this study, we aimed to analyse the correlation between the random urine protein/creatinine ratio (UPCR) and 24-h urine protein and to explore the clinical value of UPCR in the diagnosis of preeclampsia. Method: We retrospectively evaluated 109 pregnant women from our hospital who had hypertensive diseases. They were grouped according to time of urine collection and disease severity to compare differences in random urine protein, urine creatinine, and UPCR. The correlation between the UPCR and 24-h urine protein was determined by Pearson's linear correlation. Results: We found no statistically significant differences in random urine protein, urine creatinine, or UPCR among the four time of sampling groups. Further, random urine protein, UPCR, and 24-h urine protein between the gestational hypertension and preeclampsia groups differed significantly (P < 0.001). Correlation analysis showed significant positive correlation between random urine protein, and 24-h urine protein, and UPCR and 24-h urine protein, with r values of 0.789 and 0.810, respectively. According to the receiver operating characteristic (ROC) curve, the optimal threshold, sensitivity, specificity, and area under the curve of UPCR for the diagnosis of preeclampsia were 0.456 g/mmol, 67.8 %, 78.3 %, and 0.747, respectively (95 % confidence interval [CI], 0.65-0.844). Conclusion: This study indicated that UPCR is significantly correlated with 24-h urine protein and is expected to replace the 24-h urine protein test as a diagnostic indicator of preeclampsia.

Deep convolutional neural network for hippocampus segmentation with boundary region refinement.

Accurately segmenting the hippocampus from magnetic resonance (MR) brain images is a crucial step in studying brain disorders. However, this task is challenging due to the low signal contrast of hippocampal images, the irregular shape, and small structural size of the hippocampi. In recent years, several deep convolutional networks have been proposed for hippocampus segmentation, which have achieved state-of-the-art performance. These methods typically use large image patches for training the network, as larger patches are beneficial for capturing long-range contextual information. However, this approach increases the computational burden and overlooks the significance of the boundary region. In this study, we propose a deep learning-based method for hippocampus segmentation with boundary region refinement. Our method involves two main steps. First, we propose a convolutional network that takes large image patches as input for initial segmentation. Then, we extract small image patches around the hippocampal boundary for training the second convolutional neural network, which refines the segmentation in the boundary regions. We validate our proposed method on a publicly available dataset and demonstrate that it significantly improves the performance of convolutional neural networks that use single-size image patches as input. In conclusion, our study proposes a novel method for hippocampus segmentation, which improves upon the current state-of-the-art methods. By incorporating a boundary refinement step, our approach achieves higher accuracy in hippocampus segmentation and may facilitate research on brain disorders.

Lymphotoxin ß receptor activation promotes mRNA expression of RelA and pro-inflammatory cytokines TNFα and IL-1ß in bladder cancer cells.

The role of inflammation in tumorigenesis and development is currently well established. Lymphotoxin ß receptor (LTßR) activation induces canonical and noncanonical nuclear factor (NF)­κB signaling pathways, which are linked to inflammation­induced carcinogenesis. In the present study, 5,637 bladder cancer cells were cultured and the activation of LTßR was induced by functional ligand, lymphotoxin (LT) α1ß2, and silencing with shRNA. Reverse transcription­quantitative polymerase chain reaction was utilized to detect the mRNA expression levels of NF­κB family members RelA and RelB, cytokines including LTα, LTß, tumor necrosis factor (TNF)α, TNF superfamily member 14, interleukin (IL)­6 and IL­1ß, and proliferation­related genes including CyclinD1 and Survivin. The expression of phospho­p65 was determined by western blotting. Activation of LTßR on bladder cancer 5,637 cells was demonstrated to upregulate the mRNA expression levels of the RELA proto­oncogene, RelA, by 2.5­fold compared with unstimulated cells, while no significant change was observed in the RELB proto­oncogene NF­κB member mRNA levels. Expression of pro­inflammatory cytokines tumor necrosis factor (TNF)α and interleukin (IL)­1ß mRNA levels were significantly increased nearly 5­fold and 1.5­fold, respectively, following LTßR activation compared with unstimulated cells. The LTßR­induced upregulation of RelA, TNFα and IL­1ß was decreased by ~33, 27, and 26% respectively when LTßR was silenced via short hairpin RNA. Activation of LTßR had no effect on 5,637 cell growth, despite CyclinD1 and Survivin mRNA levels increasing by ~2.7 and 1.3­fold, respectively, compared with unstimulated cells. In conclusion, activation of LTßR induced the expression of RelA mRNA levels. LTßR activation might be an important mediator in promoting an inflammatory microenvironment in bladder cancer, via the upregulation of TNFα and IL­1ß mRNA levels. LTßR may be a potential therapeutic target for bladder cancer.

Decreased programmed death-1 expression on the T cells of patients with ankylosing spondylitis.

BACKGROUND: Programmed death-1 (PD-1) plays a vital role in down-modulating immune responses and maintaining peripheral tolerance. METHODS: The authors have investigated the inducible expression of PD-1 on activated T cells from patients with ankylosing spondylitis (AS). Thirty patients with AS and 31 unrelated healthy controls (HCs) were recruited in this study. The expression of PD-1 on T cells harvested from nonstimulated (t0) or stimulated cultures with phytohemagglutinin for 24 hours (t24) was determined by flow cytometry. The multiple levels of the PD-1 expression on stimulated and nonstimulated cells from each individual's sample (t24/t0) represented as the degree of the inducible effect on PD-1 expression. RESULTS: The expression of PD-1 on nonstimulated T cells presented no significant difference between AS group and HC group (P > 0.05). After stimulation, the degree of effect on PD-1 expression of CD4+, CD4+CD25+, CD4+CD25 high, CD4+CD25 low and CD4+CD25- T cells were significantly lower in patients with AS than those in HC group (1.9 ± 0.9 versus 3.6 ± 2.3, 9.7 ± 7.4 versus 17.8 ± 12.6, 87.8 ± 48.6 versus 157.3 ± 117.0, 3.7 ± 1.4 versus 7.3 ± 2.4, 0.5 ± 0.3 versus 1.1 ± 0.6, respectively, P < 0.05). However, there was no significant difference of the effect on all lymphocytes and CD8+ T cells between patients with AS and HCs (P > 0.05). CONCLUSIONS: The decreased inducible expression of PD-1 on active T lymphocytes, especially on CD4+CD25 high and CD4+CD25+ T cells, may be one of important factors involved in the development of AS.

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males.

INTRODUCTION: Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa. MATERIAL AND METHODS: 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression. RESULTS: 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues. CONCLUSIONS: The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.

Estrogen receptor alpha gene polymorphisms and breast cancer risk: a case-control study with meta-analysis combined.

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-α gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location.