COL7A1基因复合杂合变异所致的隐性营养不良型大疱性表皮松解症家系的遗传学分析

目的对1个隐性营养不良型大疱性表皮松解症家系进行基因检测及产前诊断。方法利用PCR-Sanger测序技术检测患者COL7A1基因的全部外显子及其侧翼区的潜在变异,之后进行家系验证及产前基因诊断。结果Sanger测序显示患者COL7A1基因存在c.7289delC(p.Pro2430Glnfs*36)及c.7474C>T(p.Arg2492*)复合杂合变异,分别遗传自其母亲和父亲,在100名健康对照中未检测到上述变异。产前诊断胎儿COL7A1基因c.7289位置未见变异,c.7474位置存在C>T杂合变异,判断为携带者。结论明确了1例隐性营养不良型大疱性表皮松解症家系COL7A1基因的致病性变异,并成功进行了产前诊断。     

孕妇产前诊断指征与胎儿染色体异常的关系

目的探讨产前诊断指征和产前诊断胎儿染色体异常间的关系。方法选择2018年6月至2018年12月于贵港市人民医院就诊的孕妇100例,收集所有孕妇产前诊断指征的资料,同时收集羊膜腔穿刺术检测胎儿染色体核型分析的结果。结果胎儿染色体异常共9例,总异常率占9.00%,其中无创基因检测异常组的胎儿染色体异常检出率为60.00%,明显高于高龄组的3.03%、唐氏筛查高危组的5.26%及胎儿超声异常组的7.69%,差异均有统计学意义(P<0.05);夫妇染色体异常组的胎儿染色体异常检出率为50.00%,明显高于高龄组,差异均有统计学意义(P<0.05);高龄组、唐氏筛查高危组、胎儿超声异常组间异常检出率无明显差异(P>0.05)。结论产前诊断指征与胎儿染色体异常密切相关,羊膜腔穿刺行染色体核型分析,能够有效检出胎儿染色体异常,对于有产前诊断指征的孕妇应尽早接受产前诊断,以降低新生儿出生缺陷的发生率。     

Efficient Polymer Solar Cells Based on New Random Copolymers with Porphyrin‐Incorporated Side Chains

Two new wide bandgap block copolymers (PL1 and PL2) with porphyrin‐incorporated side chains are designed and used as electron donors for solution‐processed bulk heterojunction polymer solar cells. The photophysical, electrochemical, and photovoltaic properties, charge transport mobility and film morphology of these two block copolymers are investigated. Detailed investigations reveal that the different alkyl groups and electron‐withdrawing substituents on the porphyrin pendant units have significant influence on the polymer solubility, absorption energy level, band gap, and charge separation in the bulk‐heterojunction thin films, and thus the overall photovoltaic performances. Organic photovoltaic devices derived from these copolymers and ([6,6]‐phenyl‐C₇₁‐butyric acid methyl ester) (PC₇₁BM) acceptor show the best power conversion efficiencies of 5.83% and 7.14%, respectively. These results show that the inclusion of a certain proportion of side chain porphyrin group as a pendant in the traditional donor‐acceptor (D‐A) type polymer can broaden the molecular absorption range and become a full‐color absorbing molecule. The size of the porphyrin pendant also has an obvious effect on the properties of the molecule.     

Involvement of cysteinyl leukotriene receptor 1 in Aβ1–42-induced neurotoxicity in vitro and in vivo

Accumulation of amyloid-β (Aβ) is thought to be associated with the progressive neuronal death observed in Alzheimer's disease, but the mechanisms underlying neurotoxicity triggered by Aβ remain elusive. In the current study, we investigated the roles of cysteinyl leukotriene receptor 1 (CysLT₁R) in Aβ_1–42-induced neurotoxicity in vitro or in vivo. In vitro exposure of mouse primary neurons to Aβ_1–42 caused a gradual increases in CysLT₁R expression. In vivo bilateral intrahippocampal injection of Aβ_1–42 also elicited time-dependent increases of CysLT₁R expression in the hippocampus and cortex of mice. The CysLT₁R antagonist pranlukast not only reversed Aβ_1–42-induced upregulation of CysLT₁R, but also suppressed Aβ_1–42-triggered neurotoxicity evidenced by enhanced nuclear factor-kappa B p65, activated caspase-3, decreased B-cell lymphoma-2 and cell viability and impaired memory. Furthermore, chronic treatment with pranlukast produced similar beneficial effects on memory behavior and hippocampal long-term potentiation to memantine or donepezil in intrahippocampal Aβ_1–42-injected mice. Our data indicate that CysLT₁R is involved in Aβ_1–42-induced neurotoxicity, and that blockade of CysLT₁R, such as application of CysLT₁R antagonist, could be a novel and promising strategy for the treatment of Alzheimer's disease.     

Dual-mode US/MRI nanoparticles delivering siRNA and Pt(iv) for ovarian cancer treatment

As known to all, ovarian cancer ranks the most lethal of the gynecological malignancies. The antitumor drugs based on platinum are first-line chemotherapy drugs for ovarian cancer. However, their therapeutic efficiency is severely limited owing to dose-limiting toxicities of platinum. New theranostic strategies to overcome chemotherapy toxicity is highly desirable. Meanwhile, the real-time treating effect is not visible for doctors. Herein, we constructed PFH/siRNA/Fe₃O₄@Pt(iv) NPs-cRGD (NPs-cRGD) for precise theranostics against ovarian tumors with real-time imaging. The NPs-cRGD had a good storage stability and resisted the serum-induced aggregation, which was beneficial for drug delivery. Additionally, gel-retardation assay demonstrated that the NPs-cRGD exhibited great protection to siRNA to resist nuclease degradation. In vitro, the NPs-cRGD showed good dual-mode US/MRI imaging and the relative imaging research was also discussed. Moreover, the in vitro experiments indicated that the NPs-cRGD with US exhibited excellent antitumor therapeutic efficiency, resulting from the cRGD ligands and US exposure enhanced the cellular uptake efficiency. Thus, the dual-mode nanoparticles in this work may provide precious insight into the development of various multi-mode nanoplatforms delivering drugs or genes for precise theranostics against various cancer.

Phase-shifted dual-mode US/MRI nanoparticles (PFH/siRNA/Fe₃O₄@Pt(iv) NPs-cRGD) delivering si-survivin and Pt(iv) prodrug for enhancing ovarian cancer treatment and realizing real-time monitoring.     

New spirobisnaphthalenes from an endolichenic fungus strain CGMCC 3.15192 and their anticancer effects through the P53–P21 pathway

Natural products from fungi have remained a rich resource for drug discovery. Here we report the isolation of three new spirobisnaphthalenes, namely sacrosomycin A-C (1–3), and three known analogues (4–6), from the ethyl acetate extract of a nonsporulating endolichenic fungus derived from Peltigera elisabethae var. mauritzii. The structures of these compounds were elucidated by IR, UV, MS, and NMR. Biological functions of these compounds were evaluated using cultured human cancer cell lines. Short-term cell growth and long-term cell survival assays show that compound 5 demonstrated the strongest cancer cell growth inhibition effect. We reveal that compound 5 induced both cell cycle arrest at the G2/M phase and cell death. Using western blotting, luciferase reporter assay and quantitative PCR (qPCR), we show that compound 5 induced up-regulation of the P53–P21 pathway, supporting the cell cycle arrest and growth inhibition effect of this compound. In contrast, these compounds did not induce cell death in a normal cell line. These results demonstrate a potential anticancer effect of this rare family of spirobisnaphthalene compounds isolated from endolichenic fungi.

New spirobisnaphthalenes from an endolichenic fungus strain and their anticancer effects mediated by the P53–P21 pathway.     

Ciliated muconodular papillary tumor of the lung: A newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: A case report and review of literature

We report the case of a 68‐year‐old man with a newly defined rare entity of a peripheral pulmonary tumor, consisting of a nodular papillary lesion with papillary structures containing ciliated columnar and goblet cells, as well as floating tumor cells in the mucin pool. The conspicuous mucin pool was observed to be mimicking colloid adenocarcinoma in a low‐power view, particularly in a frozen section slide. We originally reported it as an adenocarcinoma during intraoperative consultation. Immunohistochemically, the tumor cells exhibited a similar immunophenotype to pulmonary adenocarcinoma, except for the presence of focal ciliated and basaloid cells, which we found using CK5/6 and P63 immunostaining. No KRAS or EGFR mutation was found. We revised the diagnosis to that of a ciliated muconodular papillary tumor (CMPT). Four years after a wedge resection, the patient remained free of tumors. Although the malignant potential of CMPT cannot be ignored, a wedge resection with a safe margin might be a treatment option for CMPT patients.     

The direct electrochemistry and bioelectrocatalysis of nitrate reductase at a gold nanoparticles/aminated graphene sheets modified glassy carbon electrode

It is rather difficult to achieve the direct electrochemistry of nitrate reductase (NR) as it is a complex homodimeric enzyme. However, in this study, the direct electron transfer between NR''s redox centers and the electrode surface was achieved with the aid of aminated graphene sheets (am-GSs) which could immobilize NR stably and control the orientation of the enzyme molecules on the surface of the modified electrode through electrostatic attractions. Moreover, when the gold nanoparticles (AuNPs) which could act as electronic wire were introduced to the modified electrode, the NR-based enzymatic reduction of nitrate was promoted and a sensitive electrochemical response regarding the electrochemical reduction of nitrate could be obtained at the NR/AuNPs/am-GSs/GC electrode. Under optimized conditions, a wide linear range from 1.0 × 10⁻⁶ mol L⁻¹ to 2.0 × 10⁻³ mol L⁻¹ was acquired with a low detection limit of 7 × 10⁻⁷ mol L⁻¹ (S/N = 3). The biosensor was successfully employed to determine the total nitrogen in environmental water samples and the results were in good accordance with those obtained by ultraviolet-visible spectrophotometry.

The aminated graphene sheets could immobilize nitrate reductase stably and control its orientation through electrostatic attractions, achieving its direct electrochemistry.