Cobalt-catalyzed C(sp3)–H/C(sp2)–H oxidative coupling between alkanes and benzamides

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored. This protocol achieves direct C–C formation without using alkyl or aryl halide surrogates and exhibits high practicality with ample substrate scope. The method provides a new way to construct linear and five- or six-membered ring moieties in bioactive molecules.

A direct cobalt-catalyzed oxidative coupling between C(sp²)–H in unactivated benzamides and C(sp³)–H in simple alkanes, ethers and toluene derivatives was explored.     

Direct C–H functionalization of difluoroboron dipyrromethenes (BODIPYs) at β-position by iodonium salts

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed, which provides facile access to a variety of mono-substituted BODIPY dyes. Interestingly, β-styryl BODIPY compound 9b exhibits apparent cytotoxicity after laser irradiation, which has great potential for photodynamic therapy.

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed and β-styryl BODIPY 9b has great potential for photodynamic therapy.     

肥胖与雌性幼龄SD大鼠青春发育提前的相关性

目的 探讨肥胖与雌性幼龄SD大鼠与青春发育提前之间的相关性。方法 将10只雌性SD大鼠与6只雄性SD大鼠随机分为两组,分别为亲代模型组(雌鼠n=5,雄鼠n=3)、亲代对照组(雌鼠n=5,雄鼠n=3)。模型组以高脂饲料饲喂8周造模,对照组用普通大鼠饲料饲喂,8周后筛选体质量大于对照组20%的模型组亲代大鼠体进行交配,繁殖的雌性仔鼠设定为模型组仔鼠,亲代对照组大鼠繁殖的雌性仔鼠作为对照组仔鼠。模型组仔鼠造模方法与模型组亲代大鼠相同,均为同配方高脂饲料饲喂,21日龄断乳后饲喂5周,对照组仔鼠则用普通饲料饲喂5周。自21日龄起每日观察仔鼠阴门开启情况,阴门开启后每日均进行阴道涂片检查,观察动情周期,并称量体重;体长及腹围的测量每两周进行1次;两组实验仔鼠均在56日龄时结束实验,腹主动脉取血,检测两组幼鼠56日龄血清胆固醇(CH)、甘油三酯(TG)、血清卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E2)。实验结束后解剖56日龄仔鼠,取材子宫、卵巢,计算卵巢指数、子宫指数,子宫、卵巢做病理切片HE染色,计数卵巢最大横截面黄体个数和成熟卵个泡数。结果 ①56日龄造模结束,模型组幼鼠体重、腹围均高于对照组幼鼠,P<0.001;②模型组幼鼠血清TG、CH均高于对照组,P<0.001;③模型组幼鼠血清LH、E2浓度高于对照组幼鼠,P<0.001,血清FSH浓度低于对照组,P<0.001;④模型组幼鼠卵巢病理切片中最大横截面黄体计数较对照组多,P<0.001;成熟卵泡计数少于对照组,P<0.001;⑤Pearson相关性分析结果为:幼龄SD大鼠体质量与第一次动情间期、阴门开启时间两项指标呈成负相关,与血清LH、卵巢最大横截面切片黄体计数两项指标成正相关;幼龄SD大鼠腹围与第一次动情间期出现时间、阴门开启时间两项指标成负相关,与血清LH、卵巢最大横截面切片黄体计数两项指标成正相关。结论 幼龄SD大鼠青春发育评判指标与肥胖指标具有相关性,呈正相关。即具有肥胖特征的幼龄SD大鼠青春发育较之正常对照组幼鼠提前。     

三种不同严重程度大鼠重症胰腺炎模型比较研究

目的 为研究者选择合适的牛磺胆酸钠浓度来制备大鼠重症胰腺炎(severe acute pancreatitis,SAP)SAP模型提供依据。方法 将60只SD大鼠随机分为假手术组、1.5%浓度组、3.5%浓度组和5%浓度组, 造模各组分别用1.5%、3.5%和5%牛磺胆酸钠按逆行胆胰管注射法制备SAP模型。术后统计各组大鼠的死亡率;检测血清淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平;观测各组大鼠胰腺组织HE染色病理评分。结果 5%浓度组死亡率较1.5%浓度组显著升高, 血淀粉酶、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平、出血和腺泡组织坏死的病理评分较1.5%浓度组和3.5%浓度组均有显著升高。结论 5%的牛磺胆酸钠逆行胆胰管注射法能更好的制备SAP模型, 且更符合SAP的生理、病理表现。     

实验动物运输福利的研究进展

运输是实验动物行业的必要环节,运输过程的装卸、装载密度、运输时间、禁食禁水、运输笼盒、环境温度等因素如控制不当,均会使实验动物产生应激。本文介绍了国内外动物运输福利法规,从运输过程中对被运输动物产生应激影响的因素进行了探讨,总结了实验动物运输中减少动物应激的措施和方法。     

Dynamics revelation of conformational changes and binding modes of heat shock protein 90 induced by inhibitor associations

Heat shock protein 90 (Hsp90) has been an attractive target of potential drug design for antitumor treatment. The current work integrates molecular dynamics (MD) simulations, calculations of binding free energy, and principal component (PC) analysis with scanning of inhibitor–residue interaction to probe the binding modes of inhibitors YK9, YKJ and YKI to Hsp90 and identify the hot spot of the inhibitor–Hsp90 binding. The results suggest that the introductions of two groups G1 and G2 into YKJ and YKI strengthen the binding ability of YKJ and YKI to Hsp90 compared to YK9. PC analysis based MD trajectories prove that inhibitor bindings exert significant effects on the conformational changes, internal dynamics and motion modes of Hsp90, especially for the helix α2 and the loops L1 and L2. The calculations of residue-based free energy decomposition and scanning of the inhibitor–Hsp90 interaction suggest that six residues L107, G108, F138, Y139, W162 and F170 construct the common hot spot of the inhibitor–residue interactions. Moreover the substitutions of the groups G1 and G2 in YKJ and YKI lead to two additional hydrogen bonding interactions and multiple hydrophobic interactions for bindings of YKJ and YKI to Hsp90. This work is also expected to contribute theoretical hints for the design of potent inhibitors toward Hsp90.

Heat shock protein 90 (Hsp90) has been an attractive target of potential drug design for antitumor treatment.     

MicroRNA-mediated immune modulation as a therapeutic strategy in host-implant integration

The concept of implanting an artificial device into the human body was once the preserve of science fiction, yet this approach is now often used to replace lost or damaged biological structures in human patients. However, assimilation of medical devices into host tissues is a complex process, and successful implant integration into patients is far from certain. The body's immediate response to a foreign object is immune-mediated reaction, hence there has been extensive research into biomaterials that can reduce or even ablate anti-implant immune responses. There have also been attempts to embed or coat anti-inflammatory drugs and pro-regulatory molecules onto medical devices with the aim of preventing implant rejection by the host. In this review, we summarize the key immune mediators of medical implant reaction, and we evaluate the potential of microRNAs to regulate these processes to promote wound healing, and prolong host-implant integration.     

Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Because of significant changes in their expression in cancer, miRNAs are believed to be key factors in cancer genetics and to have potential as anticancer drugs. However, the delivery of miRNAs is limited by many barriers, such as low cellular uptake, immunogenicity, renal clearance, degradation by nucleases, elimination by phagocytic immune cells, poor endosomal release, and untoward side effects. Nonviral delivery systems have been developed to overcome these obstacles. In this review, we provide insights into the development of non-viral synthetic miRNA vectors and the promise of miRNA-based anticancer therapies, including therapeutic applications of miRNAs, challenges of vector design to overcome the delivery obstacles, and the development of miRNA delivery systems for cancer therapy. Additionally, we highlight some representative examples that give a glimpse into the current trends into the design and application of efficient synthetic systems for miRNA delivery. Overall, a better understanding of the rational design of miRNA delivery systems will promote their translation into effective clinical treatments.