Organocatalytic Enantioselective Synthesis of Seven-Membered Ring with Inherent Chirality.

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

The number of cycles of adjuvant chemotherapy in stage III and high-risk stage II rectal cancer: a nomogram and recursive partitioning analysis.

OBJECTIVE: The prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival. METHODS: Four hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis. RESULTS: We found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61-0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28. CONCLUSION: In conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient's risk of death.

Development and Internal Validation of a Nomogram-Based Model to Predict Three-Year and Five-Year Overall Survival in Patients with Stage II/III Colon Cancer.

OBJECTIVE: The aim of this study was to develop a nomogram-based model to predict the three-year and five-year overall survival (OS) of patients with stage II/III colon cancer following radical resection. METHODS: A total of 1156 patients with stage II/III colon cancer who underwent radical resection at the Affiliated Hospital of Guizhou Medical University between December 2012 and December 2018 were enrolled. Lasso regression was used to screen out 12 variables: age, prealbumin, albumin, degree of differentiation, total tumor-node-metastasis (TNM) stage, T stage, N stage, prognostic nutritional index (PNI), platelet/lymphocyte count, carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9), and postoperative adjuvant chemotherapy. The data set was then randomly split into a modeling set and a validation set, and the bootstrap method was used to verify the internal validity of the final model. A nomogram was then used to present the model, and the risk groups were categorized according to the total score in the nomogram. RESULTS: This study established and developed a simple, easy-to-use predictive model that included age, degree of differentiation, N stage, CA19-9, PNI, and postoperative chemotherapy as variables. In the multivariate Cox regression analysis, only postoperative chemotherapy was identified as an independent risk factor for death in patients with colon cancer. The receiver operating characteristic curve showed that the model demonstrated good resolution, with an area under the curve of 0.803. Decision curve analysis indicated that the model had a good positive net gain, and the bootstrap method was used to verify its stability. In the OS rate, the C-index was 0.78. According to the total score of the nomogram, the risk group was layered by drawing the Kaplan-Meier (K-M) curve. In the three-year OS K-M curve, the survival rates of the low-risk group, the medium-risk group, and the high-risk group were 96%, 93%, and 82%, respectively. In the five-year OS K-M curve, the survival rates of the low-risk group, the medium-risk group, and the high-risk group were 94%, 90%, and 73%, respectively. CONCLUSION: The nomogram-based prediction model developed in this study is stable and has good resolution, reliability, and net gain. It will therefore be useful for clinicians performing risk stratification and postoperative monitoring and in the development of personalized treatment options for patients with stage II/III colon cancer.

Identification of Key Functional Modules and Immunomodulatory Regulators of Hepatocellular Carcinoma.

Despite the advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfactory due to postsurgical recurrence and treatment resistance. Therefore, it is important to reveal the mechanisms underlying HCC and identify potential therapeutic targets against HCC, which could facilitate the development of novel therapies. Based on 12 HCC samples and 12 paired paracancerous normal tissues, we identified differentially expressed mRNAs and lncRNAs using the "limma" package in R software. Moreover, we used the weighted gene coexpression network analysis (WGCNA) to analyze the expression data and screened hub genes. Furthermore, we performed pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In addition, the relative abundance of a given gene set was estimated by single-sample Gene Set Enrichment Analysis. We identified 687 differentially expressed mRNAs and 260 differentially expressed lncRNAs. A total of 6 modules were revealed by WGCNA, and MT1M and MT1E genes from the red module were identified as hub genes. Moreover, pathway analysis revealed the top 10 enriched KEGG pathways of upregulated or downregulated genes. Additionally, we also found that CD58 might act as an immune checkpoint gene in HCC via PD1/CTLA4 pathways and regulate the levels of tumor-infiltrating immune cells in HCC tissues, which might be an immunotherapeutic target in HCC. Our research identified key functional modules and immunomodulatory regulators for HCC, which might offer novel diagnostic biomarkers and/or therapeutic targets for cancer immunotherapy.

The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy.

Objective: This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen. Materials and Methods: A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred. Results: In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (p = 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times, p = 0.0035). Conclusion: The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant.

Carbon Dot-Passivated Black Phosphorus Nanosheet Hybrids for Synergistic Cancer Therapy in the NIR-II Window.

Metal-free layered black phosphorus (BP) nanosheets with an excellent photothermal effect and large surface areas have been widely applied in biomedicine but are easily oxidized in ambient conditions yielding insulating phosphorus oxides adsorbed on its surface. Several chemical-functionalized strategies have been explored to protect thin layers of BP; however, the performance of passivated BP often decreases significantly, falling behind the single BP due to the strong structure perturbation. Herein, we designed and constructed 0D/2D hybrid photothermal agents by assembling NIR-II-responsive carbon dots (NIR-II-CDs) on BP nanosheets. NIR-II-CDs improve the ambient stability of BP by isolating them from water and oxygen and enhance the photothermal properties of BP nanosheets. Such NIR-II-CD/BP hybrids strengthen the light-harvesting ability, achieving high photothermal conversion efficiencies in the NIR-I (77.3%) and NIR-II (61.4%) windows, which is significantly higher than that of pristine BP (49.5 and 28.4% at 808 and 1064 nm). Owing to the intrinsic advantage of 1064 nm laser and the excellent PTT effect of our NIR-II-CD/BP hybrids, complete tumor eradication was realized in a deep-tissue tumor model.

[Progress in goat genome studies].

The goat genome is the research basis for the protection and utilization of goat resources, which is important for breeding and improving goat breeds. At present, with the continuous improvement of goat reference genome, various important research progress in goat origin, evolution and adaptability has been achieved. In this review, we summarize the research progress in the goat genome in detail, encompassing goat genome structure, genome map (genetic, physical and comparative maps), goat high throughput sequencing and SNP chip development. We aim to provide a theoretical foundation for the development of goat genome selection.

A clinical analysis of systemic chemotherapy combined with radiotherapy for advanced gastric cancer.

This study aims to investigate the clinical efficacy of systemic chemotherapy combined with radiotherapy for advanced gastric cancer.A total of 194 advanced gastric cancer patients who were treated from 2006 to 2016 were included in this study. These patients were divided into 2 groups: chemotherapy group (n = 92) and combined chemoradiotherapy group (n = 102). The clinical efficacy of these 2 groups was compared and analyzed to explore the advantageous population and duration of radiotherapy.The remission rates in the chemotherapy group and combined chemoradiotherapy group were 73.5% and 90.6%, respectively, and median survival time was 6.7 versus 10.6 months. Furthermore, the 6-month, 1-year, and 2-year survival rates were 62% versus 83.3%, 22.8% versus 38.2%, and 7.6% versus 13.7%, respectively. All the differences were statistically significant (P < .05). In patients with distant lymph node metastasis, local advanced cancer and organ metastasis, who underwent chemotherapy + radiotherapy, the median survival time was 12.6, 11.1, and 9.8 months, respectively; and the differences were statistically significant compared with the chemotherapy group (P < .05). The median survival time in patients who received concurrent chemoradiotherapy and sequential chemoradiotherapy was 11 and 9.5 months, respectively, and the difference was not statistically significant (P > .05).Combined chemoradiotherapy significantly improved the clinical remission rate, median survival time, and the 6-month, 1-year, and 2-year survival rates in patients with advanced gastric cancer. Furthermore, the survival rate of patients with simple distant lymph node metastasis was better. Concurrent chemoradiotherapy did not significantly improve survival rate compared with sequential chemoradiotherapy.

MicroRNA-876-3p functions as a tumor suppressor gene and correlates with cell metastasis in pancreatic adenocarcinoma via targeting JAG2.

Dysregulation of microRNA (miRNA) expression in multiple cancers and their vital roles in malignant cancer progression are well investigated. The purpose of this study was to explore the biological roles of miR-876-3p in pancreatic cancer. We used genome-wide gene expression analysis in clinical pancreatic adenocarcinoma samples to identify miR-876-3p down-regulated in pancreatic cancer. We then collected 22 pairs of pancreatic cancer and the corresponding non-cancerous tissues to determine miR-876-3p level, and confirmed that miR-876-3p was significantly down-regulated in pancreatic cancer. Furthermore, functional analysis suggested that overexpression of miR-876-3p suppressed cell growth and aggressively increased cells apoptosis in BXPC-3 and PANC-1 cells, whereas down-regulation led to the opposite results. We identified Jagged2 (JAG2) as a direct target of miR-876-3p, and an inverse correlation between miR-876-3p and JAG2 was observed in pancreatic adenocarcinoma. Moreover, miR-876-3p and a JAG2 siRNA were co-transfected into both PANC-1 and BXPC-3 cells to explore the mechanism of miR-876-3p and JAG2 on pancreatic adenocarcinoma tumorigenesis. Down-regulation of JAG2 inhibited the overexpression effects of miR-876-3p, and up-regulation of JAG2 reversed the effects of overexpressed miR-876-3p. Cumulatively, these results revealed a significant role of the miR-876-3p/JAG2 axis in suppressing pancreatic adenocarcinoma cell growth and aggressiveness.

Research progress in sRNAs and functional proteins in epididymosomes.

The semen quality is a basic and the most important indicator of male reproductive health. Mammalian spermatozoa undergo a series of complex structural and functional changes in the epididymis to mature and achieve fertilization capacity. Sperm cell maturation is mediated by a complex physiological process, which is synergistically regulated by a large number of transcription factors, hormones and other signaling molecules. In recent years, there is increasing evidence supporting the notion that functional proteins and sRNA (small RNAs) in epididymosomes participate in sperm maturation and fertilization process. In this review, we summarize the biological roles of functional proteins and two major sRNAs (tRNAs and miRNAs) in sperm maturation in epididymosomes, and provide some theoretical guidance and new ideas for treatments of low fertility, infertility and other reproductive diseases in men.

The biological function of pigeon crop milk and the regulation of its production.

The pigeon (Columba livia) is one of the few birds capable of secreting nutrients to nourish squabs. During the incubation period, the crop of the parent pigeon will be thickened. When squabs are hatched, the crop milk will be secreted from the crop and fed to squabs. The nutritional benefits are similar between the pigeon crop milk and mammalian milk, and both of them are regulated by prolactin. Prolactin stimulates the proliferation of crop epithelial cells, which eventually slough to form the crop milk. Evidence suggests that the complex process may be associated with the transcription of the AnxIcp35 gene and the activation of JAK/STAT and Wnt signal pathways. In this review, we summarize the main components and the biological function of the crop milk, the histological changes of the crop and the regulatory mechanism of crop milk secretion.