PARP inhibitors for homologous recombination-deficient prostate cancer

Introduction: Prostate adenocarcinoma represents a leading cause of cancer-related mortality. Increased emphasis on understanding the molecular basis of prostate cancer has identified a substantial burden of homologous recombination (HR) pathway mutations, which are enriched in castrate-resistant disease. This discovery has yielded novel therapeutic opportunities.

Areas covered: We will discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space. Evidence for use in HR-deficient patients will be outlined with discussion of the mechanism of action for this drug class, pathways of resistance, and approaches for expanding PARP inhibitor use to non–HR-deficient prostate cancer subgroups.

Expert opinion: PARP inhibition represents an exciting tool for management of HR-inactivated CRPC. With rapid adoption of next-generation sequencing technologies and other molecular techniques, the number of patients in this category is likely to increase. Ongoing and future investigations will be critical for improved understanding of the promise and appropriate treatment sequencing of PARP inhibition and optimal options for HR-proficient and -deficient prostate cancer populations. Questions remain about the clinical significance of monoallelic vs. biallelic HR mutations, the relevance of germline vs. somatic-only mutations, and the importance of mutations in non-canonical HR genes.     

海洋来源药食同源品开发利用研究进展

海洋蕴含着丰富的生物资源,是药食同源品研究与开发的重要宝库。近年来,以虾青素及海藻多糖为代表的海洋活性成分成为健康领域的关注热点,体现了海洋来源药食同源品的独特应用潜力。以目前研究较多的几类海洋来源脂质、多糖、多肽及皂苷类药食同源品为例,分别介绍其来源、结构、生物活性、开发利用潜力等方面的研究概况,以期为海洋来源药食同源品的深入开发和利用提供参考。     

Origin and epidemic status of porcine epidemic diarrhea virus variants in China

From 2010, porcine epidemic diarrhea virus (PEDV) variants caused sequential outbreaks of disease in Asia and the United States. In this retrospective study, 49 complete spike (S) gene sequences were obtained from PEDV strains collected in China from 2014 to 2016. We observed that variant PEDV strains with novel insertions, deletions, and multiple S gene recombination types were present in China. In addition, mixed infections involving different variant strains were observed in some areas. Based on phylogenetic and recombination analyses, we determined that the newly emerged PEDV variants potentially originated via recombination between the earliest Chinese G1 genogroup strain, JS‐2004‐2 and earlier Korean pandemic strains. These findings provide important information for understanding ongoing PEDV outbreaks and suggest that novel variants make it more difficult to prevent PEDV infection.     

A recombination between two Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV‐1) vaccine strains has caused severe outbreaks in Danish pigs

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in Danish swine herds. In July 2019, PRRSV‐1 was detected in a PRRSV‐negative boar station and subsequently spread to more than 38 herds that had received semen from the boar station. Full genome sequencing revealed a sequence of 15.098 nucleotides. Phylogenetic analyses showed that the strain was a recombination between the Amervac strain (Unistrain PRRS vaccine; Hipra) and the 96V198 strain (Suvaxyn PRRS; Zoetis AH). The major parent was the 96V198 strain that spanned ORFs 1–2 and part of ORF 3 and the minor parent was the Amervac strain, which constituted the remaining part of the genome. The virus seems to be highly transmissible and has caused severe disease in infected herds despite a high level of genetic identity to the attenuated parent strains. The source of infection was presumable a neighbouring farm situated 5.8 km from the boar station.     

自体与异体肌腱微创重建踝关节外侧韧带的临床对比研究

 目的 比较应用自体半腱肌腱与同种异体肌腱微创移植重建踝关节外侧韧带的临床疗效。方法 回顾性分析2006年9月至2011年6月采用微创手术治疗慢性踝关节外侧不稳患者资料。其中应用自体半腱肌腱重建踝关节外侧韧带（自体组）32例,男19例,女13例;年龄17～62岁,平均32.4岁。同期应用同种异体肌腱重建踝关节外侧韧带（异体组）36例,男22例,女14例;年龄15～67岁,平均34.2岁。两组患者均采用相同的手术方法重建距腓前韧带及跟腓韧带。结果 自体组手术时间[（85.5±11.5） min］长于异体组[（58.1±10.2）min］,发热天数异体组[（5.5±1.5）d］长于自体组[（2.5±1.2）d］。自体组23例随访（33.5±6.7）个月,异体组26例随访（28.5±6.7）个月。美国足踝外科协会（AOFAS）踝与后足评分,自体组术前（62.3±8.2）分,术后（95.1±7.5）分;异体组术前（60.2±8.4）分,术后（94.8±5.5）分。5例患者（自体组3例、异体组2例）在不平地面行走时,踝关节有残余不稳定。自体组1例患者平整地面行走踝关节有残余不稳定。自体组无一例膝部肌腱供区功能障碍。术后AOFAS评分自体组16例为优,5例为良,2例为差;异体组17例为优,5例为良,4例为差。应力位X线片示自体组距骨倾斜角平均由14.0°减少到3.8°,异体组平均由13.0°减少到3.6°;距骨前移距离自体组平均由12.3 mm减少到4.6 mm,异体组平均由11.5 mm减少到4.3 mm。结论 自体肌腱与同种异体肌腱移植重建踝关节外侧韧带的临床疗效无差异,但自体肌腱愈合时间较异体肌腱快,而异体肌腱具有损伤小,手术简便等优点。     

CD、Flt-1基因共表达重组质粒的构建及对BT325细胞增殖的抑制作用

目的构建CD、Flt-1基因共表达重组质粒,并检测其对BT325细胞增殖抑制的影响。方法从大肠杆菌及人脐静脉内皮细胞中提取总RNA,利用逆转录聚合酶链式反应（RT-RCR）扩增CD基因和FL]r-1基因片段,应用基因重组技术将CD基因和Flt-1基因片段克隆到真核表达载体pEGFP-C1中,经酶切鉴定及DNA序列分析证实所构建的载体。转染BT325细胞株,通过MTT法和流式细胞术观察其对细胞的增殖抑制作用。结果RT--RCR方法获得CD基因和Flt-1基因片段,酶切分析和DNA测序鉴定表明重组质粒pEGFP-C1-CD-Flt-1构建成功。转染72h后实验组细胞生长速度是control组的（33．20%±5．4％）,流式细胞术发现实验组细胞的G1期细胞比例明显高于control组,细胞出现凋亡,实验组细胞的凋亡率为（19．7％±5．45％）。结论成功构建真核表达重组质粒pEGFP-c1-CD-Flt-1,其体外可抑制BT325增殖并诱导其凋亡。     

A Pilot Study Investigating the Dynamics of Pigeon Circovirus Recombination in Domesticated Pigeons Housed in a Single Loft

Pigeon circovirus (PiCV) infects pigeon populations worldwide and has been associated with immunosuppression in younger pigeons. Recombination is a common mechanism of evolution that has previously been shown in various members of the Circoviridae family, including PiCV. In this study, three groups of pigeons acquired from separate lofts were screened for PiCV, and their genome sequence was determined. Following this, they were housed in a single loft for 22 days, during which blood and cloacal swab samples were taken. From these blood and cloacal swabs, PiCV genomes were determined with the aim to study the spread and recombination dynamics of PiCV in the birds. Genome sequences of PiCV were determined from seven pigeons (seven tested PiCV positive) before they were housed together in a loft (n = 58 sequences) and thereafter from the ten pigeons from blood and cloacal swabs (n = 120). These 178 PiCV genome sequences represent seven genotypes (98% pairwise identity genotype demarcation), and they share >88% genome-wide pairwise identity. Recombination analysis revealed 13 recombination events, and a recombination hotspot spanning the 3′ prime region, the replication-associated protein (rep) gene and the intergenic region. A cold spot in the capsid protein-coding region of the genome was also identified. The majority of the recombinant regions were identified in the rep coding region. This study provides insights into the evolutionary dynamics of PiCV in pigeons kept under closed rearing systems.     

Rescue of Infectious Sindbis Virus by Yeast Spheroplast-Mammalian Cell Fusion

Sindbis virus (SINV), a positive-sense single stranded RNA virus that causes mild symptoms in humans, is transmitted by mosquito bites. SINV reverse genetics have many implications, not only in understanding alphavirus transmission, replication cycle, and virus-host interactions, but also in biotechnology and biomedical applications. The rescue of SINV infectious particles is usually achieved by transfecting susceptible cells (BHK-21) with SINV-infectious mRNA genomes generated from cDNA constructed via in vitro translation (IVT). That procedure is time consuming, costly, and relies heavily on reagent quality. Here, we constructed a novel infectious SINV cDNA construct that expresses its genomic RNA in yeast cells controlled by galactose induction. Using spheroplasts made from this yeast, we established a robust polyethylene glycol-mediated yeast: BHK-21 fusion protocol to rescue infectious SINV particles. Our approach is timesaving and utilizes common lab reagents for SINV rescue. It could be a useful tool for the rescue of large single strand RNA viruses, such as SARS-CoV-2.     

Low Recombination Firing-Through Al Paste for N-Type Solar Cell with Boron Emitter

A kind of low recombination firing-through screen-printing aluminum (Al) paste is proposed in this work to be used for a boron-diffused N-type solar cell front side metallization. A front side fire-through contact (FTC) approach has been carried out for the formation of local contacts for a front surface passivated solar cell. With a low contact resistivity (ρ_c) of 1.0 mΩ·cm², good ohmic contact between the boron-doped front surface of the silicon sample and the Al paste was realized. To obtain a good energy conversion efficiency, a balance can be achieved between the open circuit voltage (V_oc) and contact resistivity (ρ_c) of the cell by combining suitable Al powders and appropriate additives. The detailed micro-contact difference in Si/metallization between the firing-through Al paste and silver-aluminum (Ag-Al) paste was analyzed. The dark saturation current density beneath the metal contact (J_{0, metal}) of the Si/metallization region using our firing-through Al paste was discussed, which was proven to be 61% lower than using Ag-Al paste. The pseudo energy conversion efficiency of the cell using Al paste measured by Suns-V_OC was also higher than using Ag-Al paste. The role of Al paste in low surface metal recombination is discussed. The utilization of this new kind of Al paste was much cheaper and more convenient, compared to the traditional process using Ag or Ag-Al paste.