Two Helminthic Cases of Human Mummy Remains from Joseon-Period Graves in Korea

Our previous research on coprolite specimens from the mummies of Joseon Dynasty (1392–1910 CE) has revealed various species of parasite eggs. Herein, we added 2 new helminthic cases of human remains from Joseon-period graves in the Republic of Korea (Korea). The organic materials precipitated on the hip bones of 2 half-mummied cases (Goryeong and Gwangmyeong cases) were collected, rehydrated, and examined by a microscope. In the sample from Goryeong-gun (gun=County), ova of Trichuris trichiura, Clonorchis sinensis, and Metagonimus spp. were detected, and eggs of T. trichiura and A. lumbricoides were found from the sample of Gwangmyeong-si (si=City). By adding this outcome to the existing data pool, we confirm our previous estimates of Joseon-period parasite infection rates. The overall rates of A. lumbricoides, T. trichiura, and C. sinensis decreased dramatically from Joseon to the modern period. In Goryeong mummy specimen, we also found Metagonimus spp. eggs that has rarely been detected in archaeological samples so far.     

ArfGAP1 inhibits mTORC1 lysosomal localization and activation

The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid‐deficient conditions is not completely understood. Here, we identify ADP‐ribosylation factor GTPase‐activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature‐sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics.     

安徽北部地区恶性肿瘤人群卡波氏肉瘤相关疱疹病毒血清学分析

卡波氏肉瘤相关疱疹病毒是一种新发现的γ疱疹病毒(Kaposi'ssarcoma-associated herpesvirus,KSHV).在中国新疆,KSHV感染率比较高,KSHV在免疫缺陷患者和静脉吸毒者中感染率也比在普通人群中高.为了进一步研究KSHV在安徽北部地区恶性肿瘤人群中的感染率和高风险因素,初步探讨KSHV与肿瘤的发生之间相关性,研究KSHV的高发人群特点,本研究选用KSHV病毒重组蛋白ORF65、ORF 73和K8.1为抗原,利用酶联免疫吸附实验(ELISA)对500份恶性肿瘤患者血清样本及200份健康体检人群血清样本进行KSHV抗体检测,分析KSHV的感染率及危险因素.结果显示500例肿瘤患者KSHV阳性总数170例,总阳性率为34％,200份健康人群KSHV阳性总数22例,总阳性率为11％,肿瘤人群KSHV阳性率明显高于健康人群(P＜0.001).其中肺癌、肝癌、结肠癌、宫颈癌、乳腺癌样本KSHV阳性率分别为36.4％,34.1％,41.7％,28.6％,30.3％,此5组肿瘤组KSHV阳性率也分别高于健康人群,都具有统计学意义(P＜0.001).但5组肿瘤样本之间KS-HV阳性率无明显差异(P＞0.05),且各组肿瘤样本分别与性别、乙肝五项、丙肝之间无统计学意义(P＞0.05).本研究结果提示安徽北部地区恶性肿瘤患者KSHV抗体阳性率显著高于中国普通人群总体KSHV抗体阳性率,证明KSHV在恶性肿瘤人群中呈现较高比例的分布.     

Congruent spatial patterns of species richness and phylogenetic diversity in karst flora: Case study of Primulina (Gesneriaceae)

The karst landform in southern China is renowned for its high levels of species diversity and endemism. Globally, karst ecosystems are under threat from unsustainable anthropogenic disturbance and climate changes and are among the most threatened ecosystems worldwide. In this study, we used the typical karst endemic genus in southern China, Primulina Hance, as a model to identify areas within the karst landform with high diversity and to investigate congruence between phylogenetic and species‐based measures of diversity. Using phylogenetic information and species distribution data, we measured geographical patterns of diversity with four metrics: species richness (SR), corrected weighted endemism (CWE), phylogenetic diversity (PD), and phylogenetic endemism (PE). Our results revealed a high spatial congruence among SR, PD, and PE, with hotspot areas identified in the Nanling Mountains (i.e., north Guangdong and northeast Guangxi) and southeast Yungui Plateau (i.e., north and southwest Guangxi), whereas the hotspots of CWE are comparatively uniform throughout the geographic extent. The categorical analysis of neo‐ and paleoendemism identified a pattern of mixed neo‐ and paleoendemism in numerous grid cells, suggesting that karst areas in southern China have acted as both “museums” and “cradles” of plant evolution. Conservation gap analysis of hotspots revealed that the majority of prioritized hotspots (>90%) of the genus are outside of protected areas, therefore indicating the limited effectiveness of national nature reserves for the karst flora. Overall, our results suggest that the karst flora merits more conservation attention and SR can be an effective surrogate to capture PD in conservation planning.     

澳洲坚果MtMADS1-like基因的克隆与表达分析

MADS～box家族基因广泛分布于植物中,在植物花发育的整个阶段起着至关重要的作用.为了探索MADS-box基因在澳洲坚果花发育过程中的分子机理,本研究以澳洲坚果'695'为试材,采用RT-PCR及RACE技术克隆获得澳洲坚果MADS-box类转录因子基因cDNA全长,命名MtMADS1-like(GenBank登录号:MK491608).该基因全长967 bp,开放阅读框ORF长672 bp,编码223个氨基酸,5'-UTR和3'-UTR分别为58 bp和237 bp.序列分析表明,MtMADS1-like具有保守的MADS-box结构域(MADS-MEF2-like)和半保守的K-box结构域,属于Type Ⅱ型MADS-box家族基因.进化分析表明,MtMADS1-like与其他植物中MADS-box蛋白具有较高的同源性,且与猴面花(Erythranthe guttata)MADS-box家族中SVP254的同源性高达67.10％,亲缘关系最近.生物信息学分析表明MtMADS1-like属于不稳定的亲水性蛋白,不具备信号肽,属于非分泌蛋白,α-螺旋和无规则卷曲构成了二级结构的主要蛋白框架,三级结构中MADS-box结构域和K-box形成该蛋白的核心结构,并且作为转录因子定位于细胞核.qPCR分析表明,MtMADS1-like基因在不同的澳洲坚果品种中差异表达,在品种'333'中表达量最高,在品种'344'中表达量最低.研究结果为进一步验证MtMADS1-like的功能及阐明澳洲坚果花发育和开花调控的分子机制奠定了基础.     

Three‐dimensional reconstruction and comparison of vacuolar membranes in response to viral infection

The vacuole is a unique plant organelle that plays an important role in maintaining cellular homeostasis under various environmental stress conditions. However, the effects of biotic stress on vacuole structure has not been examined using three‐dimensional (3D) visualization. Here, we performed 3D electron tomography to compare the ultrastructural changes in the vacuole during infection with different viruses. The 3D models revealed that vacuoles are remodeled in cells infected with cucumber mosaic virus (CMV) or tobacco necrosis virus A Chinese isolate (TNV‐A^C), resulting in the formation of spherules at the periphery of the vacuole. These spherules contain neck‐like channels that connect their interior with the cytosol. Confocal microscopy of CMV replication proteins 1a and 2a and TNV‐A^C auxiliary replication protein p23 showed that all of these proteins localize to the tonoplast. Electron microscopy revealed that the expression of these replication proteins alone is sufficient to induce spherule formation on the tonoplast, suggesting that these proteins play prominent roles in inducing vacuolar membrane remodeling. This is the first report of the 3D structures of viral replication factories built on the tonoplasts. These findings contribute to our understanding of vacuole biogenesis under normal conditions and during assembly of plant (+) RNA virus replication complexes.     

Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer

IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.