Enantioselective Reductive N-Cyclization-Alkylation Reaction of Alkene-Tethered Oxime Esters and Alkyl Iodides by Nickel Catalysis.

Asymmetric cross-electrophile difunctionalization of tethered alkenes has become a powerful tool for the production of chiral cyclic scaffolds; however, the current studies all focus on carbocyclization reactions. Herein, we report an N-cyclization-alkylation reaction and thus showcase the potential of heterocyclization for accessing new enantioenriched cyclic architectures. This work establishes a new approach for enantioselective aza-Heck cyclization/cross-coupling sequence, which remains a long-standing unsolved challenge for the synthetic community. The reaction proceeds with primary, secondary, and a few tertiary alkyl iodides, and the use of newly defined ligands gave highly enantioenriched pyrrolines with improved molecular diversity under mild conditions. The presence of imine functionality allows for further structural variations.

Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis.

Background: Acute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE. Materials and Methods: Gut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated. Results: There were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907). Conclusion: The characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.

Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction.

Catalytic asymmetric dicarbofunctionalization of tethered alkenes has emerged as a promising tool for producing chiral cyclic molecules; however, it typically relies on aryl-tethered alkenes to form benzene-fused compounds. Herein, we report an enantioselective cross-electrophile divinylation reaction of nonaromatic substrates, 2-bromo-1,6-dienes. The approach thus offers a route to new chiral cyclic architectures, which are key structural motifs found in various biologically active compounds. The reaction proceeds under mild conditions, and the use of chiral t-Bu-pmrox and 3,5-difluoro-pyrox ligands resulted in the formation of divinylated products with high chemo-, regio-, and enantioselectivity. The method is applicable for the incorporation of chiral hetero- and carbocycles into complex molecules.

Ophiopogon japonicus inhibits radiation-induced pulmonary inflammation in mice.

BACKGROUND: Radiation-induced lung injury, including the acute pulmonary inflammation and chronic pulmonary fibrosis remains the major complication of thoracic radiotherapy. METHODS: In this study, we assessed the effects of Ophiopogon japonicus (O. japonicas) in inhibiting the radiation-induced pulmonary inflammation through an acute lung injury mouse model using C57BL/6 mice that received 18 Gy irradiation to the thoracic region. Starting at 4 days before radiation, mice were treated with O. japonicus or dexamethasone combined with cephalexin or vehicle daily for 14 days. RESULTS: Exposure to radiation resulted in pulmonary inflammation in mice, but treatment with O. japonicus or dexamethasone-cephalexin could both significantly reduce radiation-induced pulmonary inflammation through inhibition of IL-6, TNF-α, TGF-ß1, hydroxyproline, MDA, MMP-2 and TIMP-2 in plasma or lung tissue. In addition, through analyzing tissue damage, cytokines and inflammation-related protein at 12 weeks after irradiation, we found that the protective effect of O. japonicus was more enduring than dexamethasone-cephalexin. CONCLUSIONS: As radiation-induced lung injury is a major obstacle in thoracic radiotherapies and seriously affect the quality of patients' life. Application of O. japonicus may be a novel strategy to manage radiation-induced pulmonary inflammation.

Association of periodontal disease with oral cancer: a meta-analysis.

The objective is to evaluate the association of periodontal disease with the risk of oral cancer. Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model to pool the odds ratio (OR) according to the test of heterogeneity. A total of five eligible studies included 1,191 oral cancer patients and 1,992 healthy control subjects were analyzed. By meta-analysis, we found a significant association of periodontal disease with oral cancer [OR = 3.53, 95 % CI (1.52-8.23); P = 0.003]. Patients with periodontal disease have increased susceptibility to oral cancer.

Radiation-induced Cochlea hair cell death: mechanisms and protection.

Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini- review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC) , are claimed to be effective at reducing radiation- inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre- examined in order to minimize the damage to cochlea hair cells.

Intravenous leiomyomatosis: CT findings.

Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor. Although IVL is histologically benign, it might be aggressive in its behavior and can grow into pelvic veins and the inferior vena cava (IVC) extending into the heart chambers and pulmonary vasculature. Occasionally, it was found to have lung metastasis. We describe four cases of IVL in the IVC with a history of hysterectomy for uterine leiomyoma, one extending into the left renal vein and three growing into the right heart chamber. We report the computed tomography (CT) findings in the four cases and briefly discuss the CT features of IVL in order to help making accurately preoperative diagnosis and improve the rate of surgical resection and survival.

[Relationship between serum and placental interleukin-18 levels and preeclampsia].

OBJECTIVE: To investigate the relationship of interleukin (IL)-18 concentrations in serum and placenta and preeclampsia. METHODS: Twenty-seven patients with preeclampsia and 28 women with normal pregnancy were recruited. Blood and placenta samples were taken and serum and placental IL-18 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). The levels of IL-18 in serum and placenta were compared. RESULT: (1) The median of serum IL-18 in patients with preeclampsia was 704 ng/L, which was significantly higher than that of control group (470 ng/L, P<0.05). (2) The median of placental IL-18 in patients with preeclampsia was 105 ng/L, which was also significantly higher than that of control group (31.5 ng/L, P<0.005). CONCLUSION: Increased serum and placental levels of IL-18 were presented in preeclampsia as compared to normal pregnancy, which might offer insight into the pathogenesis of the disease.