Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones from aryl ketone O-acetyl oximes and quinones via C–H activation and C–C bond cleavage

A redox-neutral synthesis of dibenzo[b,d]pyran-6-ones from aryl ketone O-acetyl oximes and quinones has been realized via Rh(iii)-catalyzed cascade C–H activation annulation. A possible Rh(iii)–Rh(v)–Rh(iii) mechanism involving an unprecedented β-C elimination step was proposed.

A novel procedure for the synthesis of dibenzo[b,d]pyran-6-ones via Rh(iii)-catalyzed C–H activation and C–C bond cleavage is described.

The dibenzo[b,d]pyran-6-one is one of the most important structural motifs widely present in natural products with pharmacological relevance,¹ such as gut microbiota metabolites urolithins (1–4) that show anti-inflammatory, antiglycative and neuroprotective effects,^2–4 and the extracts of an endophytic fungus Cephalosporium acremonium IFB-E007 (5–7) that have pronounced anticancer activities.⁵ In addition, the related heterocyclic structure benzo[d]naphtho[1,2-b]pyran-6-one is found in some bactericidal and antitumor natural products including gilvocarcins^6,7 (8–10) chrysomycins^8,9 (11–13), etc. (Fig. 1). Therefore, a number of approaches to access dibenzo[b,d]pyran-6-ones have been developed via the intra- or inter-molecular biaryl formation as the key step.¹⁰ However, many of these methodologies require multi-step reactions, and the development of new efficient synthetic methods, especially those easy one-step reactions that are still of great interest.Open in a separate windowFig. 1Selected representative natural products.In the past decade, transition-metal-catalyzed C–H bond activation has proven to be a powerful tool in organic syntheses¹¹ and several methods for the synthesis of dibenzo[b,d]pyran-6-ones via C–H activation have been reported.¹² Actually, in 2015, our group reported Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones from N-methoxybenzamides and quinones through C–H activation annulation.¹³ Interestingly, we obtained the same products using aryl ketone O-acetyl oximes as substrates to react with quinones under Rh(iii)-catalyzed conditions in this work. Rh(iii)-catalyzed C–H activation using ketoximes as substrates has been developed for synthesis of various substituted heterocycles.¹⁴ Compared to the previous reports, this reaction undergoes a novel mechanism involving an unexpected C–C bond cleavage, which is attractive. Moreover, our study demonstrated that solvent is vital to these reactions. In 2018, we reported Rh(iii)-catalyzed annulation of aryl ketone O-acetyl oximes with quinones to synthesize 6H-benzo[c]chromenes with acetone as a co-solvent.¹⁵ Herein, we described Rh(iii)-catalyzed synthesis of dibenzo[b,d]pyran-6-ones using the same substrates without acetone (Scheme 1).Open in a separate windowScheme 1Rh(iii)-catalyzed divergent C–H activation annulation with quinones.Initially, the reaction of acetophenone O-acetyl oxime 1a with benzoquinone 2a was employed to optimize the reaction conditions (

血液系统疾病合并嗜水气单胞菌血流感染4例报告

本文报道了昆明医科大学第二附属医院4例血液系统疾病合并嗜水气单胞菌血流感染患者的诊疗及转归,进一步明确血培养重要性以及加深临床对此病的认识。 选择2017—2021年昆明医科大学第二附属医院收治的血液系统疾病合并嗜水气单胞菌血流感染的4例患者,对患者临床表现、血培养采集及嗜水气单胞菌检出时间、实验室检查、治疗及预后等临床资料进行回顾性分析。本研究中4例病例均为男性血液系统疾病患者,处于化疗后骨髓抑制期粒细胞缺乏,出现发热后采集血培养并检出嗜水气单胞菌,4例患者血培养报阳时间4~11 h。药敏检测结果显示对二代、三代、四代头孢类抗生素、喹诺酮类抗生素、碳青霉烯类抗生素敏感性较高。4例患者早期均使用亚胺培南-西司他丁钠进行经验性抗感染治疗,1例患者经积极抗感染及升白细胞等治疗后痊愈。1例患者未完成化疗,患者要求出院,后续不详。2例患者迅速发展为坏死性筋膜炎,后患者死亡。研究表明,血液系统疾病合并嗜水气单胞菌血流感染罕见但死亡率高,对于反复发热考虑感染致病的患者需尽早进行血培养确认病原体并进行药敏试验,临床治疗时应结合患者情况及时调整治疗,除抗感染治疗外同时要提升患者免疫力,警惕发展为坏死性筋膜炎。     

Aplasia Cutis Congenital - A case of large scalp and skull defects treated with conservative approach

Aplasia cutis congenita (ACC) is an uncommon congenital disease characterized by focal absence of the epidermis, subcutaneous tissue, galea, and, in rare cases, calvarial bone. We herein show that a boy born with ACC presented with a large scalp and skull defect and was treated conservatively with wet dressings. This conservative approach produced complete epithelialization of the skin defect with secondary closure of the cranial vault.     

Effect of Polymer Drag Reducer on Rheological Properties of Rocket Kerosene Solutions

Adding drag reduction agent (DRA) to rocket kerosene is an effective way to reduce the pipeline resistance of rocket kerosene transportation systems. However, so far, there have been few research reports on the effect of DRA on the rheological properties of rocket kerosene solution, especially from a microscopic perspective. In this study, coarse-grained molecular dynamics simulations were conducted to investigate the rheological properties of rocket kerosene solutions with DRAs of different chain lengths and concentrations. The results showed that the viscosity of DRA—kerosene solution is generally higher than that of pure kerosene at a low shear rate, while with an increase in shear rate, the viscosity of DRA—kerosene solution decreases rapidly and finally tends to become similar to that of pure kerosene. The shear viscosity of DRA—kerosene solution increases with an increase in chain length and concentration of polymers. Through observing the morphologic change of DRA molecules and analyzing the radius of gyration and the mean-squared end-to-end distance of polymers, it was confirmed that the rheological properties of DRA—kerosene solutions are strongly related to the degree of entanglement of polymer chains. The simulation results provide microscopic insights into the rheological behavior of DRA—kerosene solutions and clarify the intrinsic relation between the morphologic change of polymer molecules and the rheological properties of DRA—kerosene solutions.     

ARLTS1基因重组质粒对卵巢癌细胞株SKOV3生长和凋亡的影响

目的 探讨Ras超家族成员ARLTS1基因对卵巢癌细胞株SKOV3生长及凋亡的影响.方法 构建真核表达质粒pCMV-Tag 3B-ARLTSI,并转染卵巢癌SKOV3细胞株,采用RT-PCR技术和Western blot方法检测ARLTS1基因转染组、空载体pCMV-Tag 3B转染组和未转染组中ARLTS1 mRNA及蛋白表达水平,用MTT及流式细胞仪检测各组细胞生长、周期及凋亡率等生物学行为的变化,Western blot检测细胞easpase-3和bcl-2蛋白表达水平的变化.结果 真核表达质粒pCMV-Tag 3B-ARLTSI转染SKOV3细胞后,经PCR和Western blot证实转染成功.ARLTSI转染SKOV3细胞后,细胞生长明显受抑(P<0.05).流式细胞术检测发现ARLTS1基因转染组与空载体转染组及未转染组细胞相比,S期细胞比例明显增多(P=0.035和0.011,细胞凋亡率(36.7%)显著高于另两组细胞(P均<0.001).ARLTS1基因转染组细胞中caspase-3和bel-2蛋白表达水平分别下降34.9%和47.7%,与未转染组细胞相比差异有统计学意义(P<0.05).结论 ARLTS1基因转染后能抑制人卵巢癌细胞SKOV3的生长,调控SKOV3细胞周期,可能通过caspase途径促进肿瘤细胞凋亡·     

~（90）Sr照射抑制青光眼术后瘢痕形成的实验与临床研究

在动物实验的基础上，为青光眼术后瘢痕形成高危病人２３例３１只眼作小梁切除术，术后３天开始分次给予局部~（９０）Ｓｒ照射，总剂量为３０．２４Ｇｙ，结合局部用激素，随访１～２４个月（平均７个月），眼压控制率为９０．３％，未见晶体损害及其他并发症，提示作为青光眼滤过手术后抗瘢痕形成的一种方法，该治疗措施是可取的。     

雷公藤内酯对海人酸诱导大鼠脑小胶质细胞MHC分子表达的影响

目的:评价雷公藤内酯对海人酸致痫大鼠神经元的免疫保护作用。方法:结晶紫染色观察神经元形态,免疫组化技术检测小胶质细胞MHC-Ⅰ、Ⅱ类分子的表达。结果:30μg/kg雷公藤内酯可使大鼠的癫痫抽搐状态明显较海人酸组缓和,出现时间较海人酸组晚(P<0.05),且可使海人酸诱导大鼠活化小胶质细胞的数量减少,凋亡神经元数量减少。30μg/kg雷公藤内酯可下调海人酸诱导大鼠脑小胶质细胞表达MHC-Ⅰ、Ⅱ类分子(P<0.01)。结论:雷公藤内酯通过抑制小胶质细胞表达MHC-Ⅰ、Ⅱ类分子和免疫应答对海人酸诱导大鼠神经元凋亡具有免疫保护作用。     

Predictive model of postoperative pneumonia after neoadjuvant immunochemotherapy for esophageal cancer

BackgroundPostoperative pneumonia (PP) is the most common pulmonary complication of esophagectomy. It is of great importance to identify any high-risk factors and prevent pulmonary complications to improve the prognosis of patients with esophageal cancer undergoing esophagectomy. Thus, we established a predictive model of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma (ESCC), and provide suggestions for the best strategy for the perioperative period of the patients.MethodWe retrospectively analyzed 78 patients who underwent esophagectomy for squamous cell carcinoma after neoadjuvant immunochemotherapy between September 2019 and August 2021.We used the “glmnet” language package in R to perform least absolute shrinkage and selection operator (LASSO) regression to screen the best predictors of PP, and nomograms predicting PP were constructed utilizing screened factors. The performance of nomograms was internally validated by calibration curves, concordance index (C-index), and the Brier score for overall performance.ResultsTwenty-six patients (33.3%) had postoperative pneumonia. After LASSO regression, the factors that were independently associated with PP were diffusing capacity of the lungs for carbon monoxide (DLCO) (P=0.0002), white blood cell (WBC) difference before vs. after neoadjuvant immunochemotherapy (P=0.0133). We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.147, its calibration slope was 0.98, and its C-index was 0.85 (95% CI: 0.75–0.95). Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability.ConclusionsOur prediction model can predict the possibility of PP in patients with neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma and may facilitate physicians’ efforts to reduce the incidence of postoperative pneumonia.     

Fluoro-Jade C揭示小鼠匹罗卡品模型中杏仁核神经变性

目的应用Fluoro-Jade C(FJC)染色方法在小鼠匹罗卡品癫痫模型中探测杏仁核结构中神经元的变性情况,以了解杏仁核结构在慢性颞叶癫痫发生中的病理变化和癫痫反复发作的神经基础。方法雄性昆明小鼠6只(对照组3只,匹罗卡品处理组3只)。在癫痫持续状态后12 h处死处理组小鼠。在杏仁核水平切制冠状切片,行FJC染色,在荧光显微镜下观察FJC阳性细胞的形态和在杏仁核中的整体分布情况。结果在处理组,FJC染色的脑切片上可以很清楚地看到呈亮黄绿色荧光的FJC阳性细胞,呈神经元形态,胞体和突起均清晰显示。杏仁核出现大量FJC阳性细胞,而对照组未见。结论该研究在小鼠匹罗卡品癫痫模型中运用FJC染色技术显示杏仁核中发生了大量神经元变性,有利于更好地理解颞叶癫痫中中枢神经系统所发生的病理变化和自发反复发作的癫痫机制。     

MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2

The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells.Real-time PCR was employed to detect miR-21 expression in normal brain tissues,glioblastoma tissues and glioblastoma cell lines (A172,T98G and U87MG).T98G cells were transfected with anti-miR-21 oligonucleotides,or plasmids containing PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3).The survival curve was obtained to investigate the sensitivity of T98G cells to radiation.Cell apoptosis was measured by using the Caspase-3/7 kit and cell cycle by flow cytometry.Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells.The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity.Over-expression of miR-21 resulted in radiation resistance,while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation.After miR-21 knockdown,the apoptosis of T98G cells was significantly increased and the G2 phase arrest was more significant.In addition,miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2,which contributed to the apoptosis and G2 arrest of T98G cells.The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2.MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future.