METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition

Papillary thyroid cancer (PTC) is a common endocrine system malignancy all over the world. Aberrant expression of six transmembrane epithelial antigen of the prostate 2 (STEAP2) has been functionally associated with cancer progression in many cancers. Nevertheless, its biological function in PTC is still unclear. Here, we found that PTC tissues had preferentially downregulated STEAP2 as compared with noncancerous tissues. Low STEAP2 expression correlated with aggressive clinicopathological characteristics and dismal prognosis in patients with PTC. We performed gain- and loss-of-function experiments, including cell proliferation assay (Cell Counting Kit-8 assay), EdU (5-ethynyl-2′-deoxyuridine) and colony formation assays, transwell migration, and invasion assays, and constructed a nude mouse xenograft tumor model. The results demonstrated that STEAP2 overexpression inhibited PTC cell proliferation, migration, and invasion in vitro and inhibited lung metastasis and tumorigenicity in vivo. Conversely, silencing STEAP2 yielded the opposite results in vitro. Mechanistically, bioinformatics analysis combined with validation experiments identified STEAP2 as the downstream target of methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification. METTL3 stabilized STEAP2 mRNA and regulated STEAP2 expression positively in an m6A-dependent manner. We also showed that m6A-mediated STEAP2 mRNA translation initiation relied on a pathway dependent on the m6A reader protein YTHDF1. Rescue experiments revealed that silencing STEAP2 partially rescued the tumor-suppressive phenotype induced by METTL3 overexpression. Lastly, we verified that the METTL3–STEAP2 axis functions as an inhibitor in PTC by suppressing epithelial–mesenchymal transition and the Hedgehog signaling pathway. Taken together, these findings strongly suggest that METTL3-mediated STEAP2 m6A modification plays a critical tumor-suppressive role in PTC progression. The METTL3–STEAP2 axis may be a potential therapeutic molecular target against PTC.Subject terms: Metastasis, Prognostic markers     

Hematoporphyrin diethers--V. Plasma protein binding and photosensitizing efficiency

1. Binding of added hematoporphyrin (HP) ethers to human plasma proteins and lipoproteins has been investigated by ultracentrifugation. 2. The binding to low density lipoproteins (LDL) has been discussed in terms of photosensitized tumor growth delay of tumors and HPLC-retention time, i.e. degree of polarity. 3. The LDL-binding data show a uniform relationship to sensitizing efficiency and degree of polarity, the only exception being HP-diamyl ether. No such uniform relationship exists for less related dyes, such as HP, tetraphenylporphyrin tetrasulfonate and HP-dimethyl ether.     

新疆粉衣科地衣分类学研究

该研究以采自新疆的100余份粉衣科地衣标本为研究材料,通过形态解剖学、地衣化学以及分子生物学的方法鉴定出6个种和1个变种,分别为中央黑瘤衣(Buellia centralis)、丽黑瘤衣(B.elegans)、蒙古黑瘤衣(B.mongolica)、鳞饼衣(Dimelaena oreina)、鳞饼衣白磷变种(D.oreina var.exalbescens)、海登氏多瘤胞(Diplotomma hedinii)和绿色四孢黑瘤衣(Tetramelas chloroleucus),其中丽黑瘤衣、蒙古黑瘤衣和绿色四孢黑瘤衣为新疆新增粉衣科地衣新记录,至此新疆粉衣科地衣共有6属13种1变种;并提供了新疆粉衣科地衣的分种检索表、物种描述、系统发育分析以及形态解剖结构照片。     

新疆准噶尔盆地玛湖凹陷玛页1井宾夕法尼亚亚系至乌拉尔统风城组孢粉地层学研究

提要准噶尔盆地西北缘玛湖凹陷风城组主要形成于碱湖环境,含有优质生烃母岩。对玛页1井风城组岩心样品的孢粉分析建立了Protohaploxypinus perfectus–Lunatisporites tersus (PT)孢粉组合。该组合包括20属29种孢粉化石。PT组合以双气囊具肋花粉占主导,蕨类孢子含量很低为特征;孢粉母体植物类群以裸子植物门种子蕨盾籽目为主,其次为松柏纲松柏目。该组合与准噶尔盆地南缘塔什库拉组上部至乌拉泊组的Crustaesporites–Protohaploxypinus–Hamiapollenites孢粉组合可以对比,均以双气囊具肋花粉为主要特征,又同时出现重要的属种Gardenasporites bilabiatus,Triangulisaccites boleensis和Hamiapollenites saccatus。孢粉地层学和同位素年代学资料表明,玛页1井风城组PT组合的时代很可能属于石炭纪宾夕法尼亚亚纪卡西莫夫期至二叠纪乌拉尔世阿瑟尔期,玛湖凹陷区整个风城组沉积时代晚于宾夕法尼亚亚纪巴什基尔期,其上部可能包含部分乌拉尔世阿瑟尔期沉积。风城组黑色页岩中...     

紫九牛叶绿体基因组密码子偏好性分析

为确定瑶药紫九牛叶绿体基因组密码子的使用模式及其成因,该研究以紫九牛叶绿体基因组50条蛋白质编码序列为研究对象,利用Codon W 1.4.2和在线软件CUSP和Chips分析其密码子偏好性。结果表明：(1)RSCU>1的密码子有29个,其中有28个以A/U结尾,说明叶绿体基因组的同义密码子中偏好以A/U结尾。(2)紫九牛叶绿体基因组密码子的GC含量GC₁(47.38%)>GC₂(39.81%)>GC₃(29.60%),ENC值大于45的有40个,说明紫九牛叶绿体基因组存在较弱的偏性。(3)中性绘图分析和ENC-plot分析说明了紫九牛叶绿体基因组密码子的偏好性既受到选择的作用,又受到突变因素的影响。(4)通过构建的高低基因表达库最终确定了15个最优密码子,分别为UUG、AUU、GUU、GUA、UCU、 CCU、ACU、ACA、GCU、CAA、AAC、GAA、UGU、CGU和GGU。该研究为紫九牛叶绿体基因组的确定以及遗传多样性分析提供了依据。     

Safety and immunogenicity of a new glycoengineered vaccine against Acinetobacter baumannii in mice

Acinetobacter baumannii poses a serious threat to human health, mainly because of its widespread distribution and severe drug resistance. However, no licensed vaccines exist for this pathogen. In this study, we created a conjugate vaccine against A. baumannii by introducing an O-linked glycosylation system into the host strain. After demonstrating the ability of the vaccine to elicit Th1 and Th2 immune responses and observing its good safety in mouse a model, the strong in vitro bactericidal activity and prophylactic effects of the conjugate vaccine against infection were further demonstrated by evaluating post-infection tissue bacterial loads, observing suppressed serum pro-inflammatory cytokine levels. Additionally, the broad protection from the vaccine was further proved via lethal challenge with A. baumannii. Overall, these results indicated that the conjugate vaccine could elicit an efficient immune response and provide good protection against A. baumannii infection in murine sepsis models. Thus, the conjugate vaccine can be considered as a promising candidate vaccine for preventing A. baumannii infection.     

Requirements for human‐induced pluripotent stem cells

‘Requirements for Human‐Induced Pluripotent Stem Cells’ is the first set of guidelines on human‐induced pluripotent stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, and instructions for use, labeling, packaging, storage, transportation, and waste handling for human‐induced pluripotent stem cells, which apply to the production and quality control of human‐induced pluripotent stem cells. It was released by the Chinese Society for Cell Biology on 9 January 2021 and came into effect on 9 April 2021. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human‐induced pluripotent stem cells for applications.