A novel function of anaphase promoting complex subunit 10 in tumor progression in non-small cell lung cancer

The anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase, is responsible for the transition from metaphase to anaphase and the exit from mitosis. The anaphase promoting complex subunit 10 (APC10), a subunit of the APC/C, executes a vital function in substrate recognition. However, no research has reported the connection between APC10 and cancer until now. In this study, we uncovered a novel, unprecedented role of APC10 in tumor progression, which is independent of APC/C. First, aberrant increase of APC10 expression was validated in non-small cell lung cancer (NSCLC) cells and tissues, and the absence of APC10 repressed cell proliferation and migration. Of great interest, we found that APC10 inhibition induced cell cycle arrest at the G0/G1 phase and reduced the expression of the APC/C substrate, Cyclin B1; this finding is different from the conventional concept of the accumulation of Cyclin B1 and cell cycle arrest in metaphase. Further, APC10 was found to interact with glutaminase C (GAC), and the inhibition of APC10 weakened glutamine metabolism and induced excessive autophagy. Taken together, these findings identify a novel function of APC10 in the regulation of NSCLC tumorigenesis and point to the possibility of APC10 as a new target for cancer therapy.     

Cold atmospheric plasma ameliorates imiquimod-induced psoriasiform dermatitis in mice by mediating antiproliferative effects

Psoriasis is a chronic hyperproliferative skin disease characterised by excessive growth of keratinocytes. Indeed, inducing keratinocyte apoptosis is a key mechanism responsible for psoriatic plaques clearance following some important existing therapies, which display pro-oxidant activity. Cold atmospheric plasma (CAP), acting as a tuneable source of reactive oxygen and nitrogen species (RONS), can controllably transfer RONS to the cellular environment, deliver antiproliferative RONS concentrations and exert antiproliferative and proapoptotic effects. This study was undertaken to evaluate the therapeutic potential of CAP in psoriasis. We used cell models of psoriasis-like inflammation by adding lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNF-α) to HaCaT keratinocytes. Indirect plasma, plasma-activated medium (PAM), was administered to HaCaT cells. Atmospheric pressure plasma jet (APPJ) was applied directly to imiquimod (IMQ)-induced psoriasiform dermatitis in mice. The results showed that PAM induced an increase in intracellular ROS and caused keratinocyte apoptosis. Moreover, cells under inflammation showed lesser viability and larger apoptosis rate. With repeated administration of APPJ, psoriasiform lesions showed ameliorated morphological manifestation and reduced epidermal proliferation. Overall, this study supports that CAP holds good potential in psoriasis treatment.     

mRNA表观修饰方式及m6A功能研究进展

mRNA上能发生100多种化学修饰,其中N~6-腺嘌呤(m~6A)是mRNA修饰中最广泛的表观修饰方式之一。在细胞分化、胚胎发育和应激等生物学过程中,特定的mRNA会发生包括N~1-腺嘌呤甲基化、N~5-胞嘧啶甲基化、假尿嘧啶以及N`6-腺嘌呤甲基化等修饰,它们共同形成了mRNA转录后调控的表观修饰转录组,实现对mRNA翻译成蛋白质过程的精确时空调控,特别是m~6A修饰能通过调控mRNA的代谢和翻译等进而调控细胞的一系列生物学过程。文中主要综述mRNA的表观修饰类型和特点,特别是m~6A修饰参与调控mRNA和细胞生物学功能的最新研究进展,并展望了将来m~6A表观修饰的研究重点和方向。     

长链非编码RNA与宫颈癌

长链非编码RNA (Long non-coding RNA,lncRNAs)是RNA的其中一员,其结构类似于mRNA,但由于没有保守的开放阅读框,因此不能编码蛋白质。LncRNAs曾被认为是基因转录后的异常现象或噪音,没有任何的生物学功能。随着研究的进一步深入,发现其可作为重要的调控分子参与人类正常或异常的生物学活动过程。LncRNAs与神经系统功能、机体代谢紊乱以及肿瘤等疾病的发生发展密切相关。异常表达于宫颈癌的lncRNAs通过发挥抑制肿瘤或促进肿瘤的作用,参与调控宫颈癌的各个生物学过程。文中结合最新报道就lncRNAs在宫颈癌的异常调节、分子调节机制和潜在临床应用方面进行综述。     

A novel framework for evaluating in situ breeding management strategies in endangered populations

Conservation breeding management aims to reduce inbreeding and maximize the retention of genetic diversity in endangered populations. However, breeding management of wild populations is still rare, and there is a need for approaches that provide data-driven evidence of the likelihood of success of alternative in situ strategies. Here, we provide an analytical framework that uses in silico simulations to evaluate, for real wild populations, (i) the degree of population-level inbreeding avoidance, (ii) the genetic quality of mating pairs, and (iii) the potential genetic benefits of implementing two breeding management strategies. The proposed strategies aim to improve the genetic quality of breeding pairs by splitting detrimental pairs and allowing the members to re-pair in different ways. We apply the framework to the wild population of the Critically Endangered helmeted honeyeater by combining genomic data and field observations to estimate the inbreeding (i.e., pair-kinship) and genetic quality (i.e., Mate Suitability Index) of all mating pairs for seven consecutive breeding seasons. We found no evidence of population-level inbreeding avoidance and that ~91.6% of breeding pairs were detrimental to the genetic health of the population. Furthermore, the framework revealed that neither proposed management strategy would significantly improve the genetic quality or reduce inbreeding of the mating pairs in this population. Our results demonstrate the usefulness of our analytical framework for testing the efficacy of different in situ breeding management strategies and for making evidence-based management decisions.     

Genomic insights into the adaptation and evolution of the nautilus,an ancient but evolving “living fossil”

The nautilus, commonly known as a “living fossil,” is endangered and may be at risk of extinction. The lack of genomic information hinders a thorough understanding of its biology and evolution, which can shed light on the conservation of this endangered species. Here, we report the first high-quality chromosome-level genome assembly of Nautilus pompilius. The assembled genome size comprised 785.15 Mb. Comparative genomic analyses indicated that transposable elements (TEs) and large-scale genome reorganizations may have driven lineage-specific evolution in the cephalopods. Remarkably, evolving conserved genes and recent TE insertion activities were identified in N. pompilius, and we speculate that these findings reflect the strong adaptability and long-term survival of the nautilus. We also identified gene families that are potentially responsible for specific adaptation and evolution events. Our study provides unprecedented insights into the specialized biology and evolution of N. pompilius, and the results serve as an important resource for future conservation genomics of the nautilus and closely related species.     

3-D ultrastructure of O. tauri: electron cryotomography of an entire eukaryotic cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes.     

Development of a fingerprint of Salvia miltiorrhiza Bunge by high-performance liquid chromatography with a coulometric electrode array system

To standardize and control herbal medicines, a feasible approach and control system is necessary. In this paper, a high-performance liquid chromatography with a coulometric electrode array detector (HPLC-CEAD) system was applied to fingerprint Salvia miltiorrhiza Bunge (S. miltiorrhiza Bunge), a popular herbal medicine, for the first time. pH of mobile phase, working potentials and sample preparation were included in our research. Twenty-five common peaks were obtained from extracts of S. miltiorrhiza Bunge (Shandong province), more than that obtained in previous report. Fingerprints of S. miltiorrhiza Bunge from different locations were also studied. The content of main components varied in different samples. Overlapping ratio of peaks (ORP) in 10 batches of S. miltiorrhiza Bunge (Shandong province) was not less than 72.46%. In method validation, relative standard deviation (RSD) of relative retention times and relative peak areas were of not more than 3%. It was concluded that HPLC-CEAD system can be applied in fingerprinting herbal medicines.     

Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer

Exosomal proteins are emerging as relevant diagnostic and prognostic biomarkers for cancer. This study was aimed at illustrating the clinical significance of exosomal Copine III (CPNE3) purified from the plasma of colorectal cancer (CRC) patients. The CPNE3 expression levels in CRC tissues were analyzed by real-time PCR, western blot, and immunohistochemistry. Plasma exosomes were isolated to examine the CPNE3 level using ELISA. Pearson’s correlation analysis was performed to investigate the CPNE3 levels between CRC tissues and matched plasma samples. Receiver operating characteristic curve analysis was developed to measure the diagnostic performance of exosomal CPNE3. The Kaplan–Meier method and Cox's proportional hazards model were utilized to determine statistical differences in survival times. CPNE3 showed increased expressions in the CRC tissues. A moderately significant correlation was found between CPNE3 expression in CRC tissues by immunohistochemistry and matched serum exosomal CPNE3 expression by ELISA (r = 0.645,(r = 0.645, p < 0.001). < 0.001). Exosomal CPNE3 yielded a sensitivity of 67.5% and a specificity of 84.4% in CRC at the cutoff value of 0.143 pg per 1ug1 ug exosome. Combined data from carcinoembryonic antigen and exosomal CPNE3 achieved 84.8% sensitivity and 81.2% specificity as a diagnostic tool. CRC patients with lower exosomal CPNE3 levels had substantially better disease-free survival (hazard ratio [HR], 2.9; 95% confidence interval [CI]: 1.3–6.4; p = 0.009) = 0.009) and overall survival (HR, 3.4; 95% CI: 1.2–9.9; p = 0.026) = 0.026) compared with those with higher exosomal CPNE3 levels. Exosomal CPNE3 show potential implications in CRC diagnosis and prognosis.