BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16.
METHODS: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively.
RESULTS: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes.
CONCLUSIONS: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.

Obesity is often associated with low-grade inflammation. The incidence of obesity has increased annually worldwide, which seriously affects human health. A previous study indicated that long noncoding RNA SNHG12 was downregulated in obesity. Nevertheless, the role of SNHG12 in obesity remains to be elucidated. In this study, qRT-PCR, western blot, and ELISA were utilized to examine the gene and protein expression. Flow cytometry was employed to investigate the M2 macrophage markers. RNA pull-down assay and RIP were utilized to confirm the interactions of SNHG12, hnRNPA1, and HDAC9. Eventually, a high-fat diet-fed mouse model was established for in vivo studies. SNHG12 overexpression suppressed adipocyte inflammation and insulin resistance and promoted M2 polarization of macrophages that was caused by TNF-α treatment. SNHG12 interacted with hnRNPA1 to downregulate HDAC9 expression, which activated the Nrf2 signaling pathway. HDAC9 overexpression reversed the effect of SNHG12 overexpression on inflammatory response, insulin resistance, and M2 phenotype polarization. Overexpression of SNHG12 improved high-fat diet-fed mouse tissue inflammation. This study revealed the protective effect of SNHG12 against adipocyte inflammation and insulin resistance. This result further provides a new therapeutic target for preventing inflammation and insulin resistance in obesity.

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.

目的： 探讨儿童肾脏透明细胞肉瘤（CCSK）的临床病理学特征、诊断及预后。 方法： 收集首都医科大学附属北京儿童医院及河南省儿童医院2016年1月至2022年6月诊断的46例CCSK，观察其临床特征、组织学形态、免疫组织化学、分子遗传学特征及预后。 结果： 46例患者男性30例，女性16例，发病年龄3个月至11岁（中位年龄3岁），均为单侧，肿瘤最大径4.5~19.0 cm（中位数11 cm）；Ⅰ期15例，Ⅱ期26例，Ⅲ期4例，Ⅳ期1例；组织学除经典型外，常混有2~5种组织学亚型。术后25例（54.3%）转移和/或复发，5例死亡，复发时间1~107个月不等（中位数16个月），远处转移部位主要是肺、骨、脑。肿瘤最大径与无进展生存率存在相关性，临床分期与总生存率差异具有统计学意义。免疫组织化学标志物BCOR、Cyclin D1具有高灵敏度；分子病理检测显示89.1%（41/46）存在BCOR基因第15号外显子内部串联重复，2.2%（1/46）YWHAE-NUTM2重排，2.2%（1/46）BCOR-CCNB3基因融合，三者互斥，三者联合检测阳性率达93.5%（43/46）。 结论： CCSK好发于婴幼儿，肿瘤体积和分期与预后相关，组织病理联合免疫组织化学和分子检测可显著提高诊断准确性。.

BACKGROUND The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been extensively studied since next-generation sequencing (NGS) technology became widely available. However, research has mainly focused on the relationship between donor CH mutations and transplant prognosis, and research into the relationship between CH mutations in the recipient and acute graft-versus-host disease (aGVHD) is lacking. MATERIAL AND METHODS We analyzed NGS results and their correlation with aGVHD and prognosis in 196 AML patients undergoing allo-HSCT. RESULTS A total of 93 (47.4%) patients had CH mutations. The most frequently mutated genes were DNMT3A (28 of 196; 14.3%), TET2 (22 of 196; 11.2%), IDH1 (15 of 196; 7.7%), IDH2 (14 of 196; 7.1%), and ASXL1 (13 of 196; 6.6%). The incidence of aGVHD was higher in patients older than 45 years old with DTA mutations (DNMT3A, TET2 or ASXL1). DNMT3A mutation but not with TET2 or ASXL1 mutation was an independent risk factor for aGVHD in patients receiving allo-HSCT older than 45 years old. With a median follow-up of 42.7 months, CH mutations were not associated with overall survival and leukemia-free survival. CONCLUSIONS DNMT3A mutation, but not TET2 or ASXL1 mutation, was associated with higher incidence of aGVHD.

UNASSIGNED: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood.
UNASSIGNED: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts.
UNASSIGNED: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.
UNASSIGNED: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.

OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism.
METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed.
RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00).
CONCLUSIONS: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.
UNASSIGNED: 骨髓增殖性肿瘤患者DTA突变与血栓栓塞关系研究.
UNASSIGNED: 分析骨髓增殖性肿瘤（MPN）患者DTA（DNMT3A、TET2和ASXL1）基因突变情况，并探讨DTA突变与血栓栓塞的关系。.
UNASSIGNED: 回顾性分析2016年9月至2022年9月在山东第一医科大学附属中心医院确诊的62例初诊MPN患者的临床资料,采用二代测序检测技术对35种MPN相关基因进行检测，分析MPN患者DTA突变情况及其与血栓栓塞事件的关系。.
UNASSIGNED: 75.8%（47/62）的患者可检测出非驱动基因突变，每个患者的平均突变数为1.08个，发生突变的非驱动基因主要有TET2（38.7%，24/62）、DNMT3A（9.7%，6/62）及ASXL1（6.5%，4/62）。62例MPN患者中31例（50.0%）检出DTA基因突变，主要与驱动基因伴随出现；≥60岁的MPN患者DTA突变率明显高于<60岁的患者(P =0.039)。存在DTA突变的患者血栓栓塞发生率为58.1%(18/31)，明显高于无DTA突变的MPN患者（19.4%，6/31）（P =0.002）。发生血栓栓塞的患者的TET2基因突变率为66.7%（16/24），显著高于未发生血栓栓塞患者的TET2基因突变率（21.1%，8/38）（P =0.00）。.
UNASSIGNED: MPN患者DTA突变发生率较高，主要与驱动基因突变伴随发生。DTA突变的MPN患者血栓栓塞发生率明显高于无DTA突变的患者，尤其是伴有TET2突变的老年患者需警惕血栓栓塞事件的发生。.

暂无摘要。

BACKGROUND: Genetic mutations play a crucial role in the development and progression of myelodysplastic syndromes (MDS), impacting the immune microenvironment and influencing the choice of treatment regimen, as well as the efficacy and prognosis of patients. The objective of this study was to examine variations in hematological and immunological characteristics associated with common gene mutations in MDS patients and establish a foundation for the precise treatment of MDS.
METHODS: The hematological, immunological, and other clinical features of 71 recently diagnosed MDS patients from January 1, 2019, to July 31, 2023, were retrospectively analyzed. These patients were categorized based on their gene mutations, and the variances in hematological and immunological characteristics among distinct groups were compared.
RESULTS: Hematological variances were observed among different gene mutation groups. Specifically, platelet counts in the splicing factor 3B subunit 1 (SF3B1) mutation group were notably higher compared to the wild-type group (p = 0.009). Conversely, in the additional sex combs like 1 (ASXL1) mutation groups, monocyte ratios were significantly elevated in comparison to the wild-type group (p = 0.046), and in the ten-eleven translocation 2 (TET2) mutation group, lymphocyte ratios were significantly lower (p = 0.022). Additionally, the leukocyte (p = 0.005), neutrophil ratio (p = 0.002), and lymphocyte ratio (p = 0.001) were significantly higher in the Runt-related transcription factor 1 (RUNX1) mutation group. Regarding immunological distinctions, the Natural Killer (NK) cell ratio demonstrated a significant increase in the SF3B1 mutation group (p = 0.005). Moreover, the TET2 mutation group exhibited a significantly higher Interleukin-8 (IL-8) level (p = 0.017). In contrast, the U2 small nuclear RNA auxiliary factor 1 (U2AF1) group displayed significantly lower levels of IL-1β (p = 0.033), IL-10 (p = 0.033), and Tumour Necrosis Factor-α (TNF-α) (p = 0.009).
CONCLUSIONS: Distinct variations exist in the immune microenvironment of MDS associated with different genetic mutations. Further studies are imperative to delve into the underlying mechanisms that drive these differences.

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.