[This corrects the article DOI: 10.7150/ijms.21113.].

Hepatocellular carcinoma (HCC) is a malignancy that is notorious for its dismal prognosis. Dysregulation of the tumor microenvironment (TME) in HCC has emerged as a key hallmark in determining disease progression and the response to immunotherapy. The aim of this study was to identify novel TME regulators that contribute to therapeutic resistance, thus providing mechanistic insights for targeted interventions. The expression of SMIM25 was evaluated in the the Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC) and Guangxi HCC cohorts, and its clinicopathological significance was assessed. RNA sequencing and bioinformatics analyses were performed to elucidate the potential impact of elevated SMIM25 levels. Immunohistochemistry (IHC) and single-cell mass cytometry (CyTOF) were employed to examine the cellular composition of the tumor microenvironment. The biological effects of SMIM25 on cell proliferation and migration were studied in vitro using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide(MTT) and wound healing assays, while its impact on tumor growth was evaluated in vivo in a nude mouse model. Transcriptomic and single-cell proteomic analyses were integrated to explore the mechanism by which SMIM25 affects the progression of HCC. The expression of SMIM25 was significantly up-regulated in both HCC tissues and cell lines (p < 0.05). RNA sequencing analyses revealed a significant positive correlation between SMIM25 expression and immunosuppression, and between SMIM25 expression and extracellular matrix(ECM)-related molecular features. Single-cell mass cytometry revealed two immunosuppressive cell clusters that were enriched in HCC patients with high SMIM25 expression. Moreover, SMIM25 was associated with immune exclusion and ECM remodeling signals in the TME of HCC. SMIM25 overexpression was associated with the expression of the tumor inflammatory marker cyclooxygenase-2(COX-2), and a COX-2 inhibitor could partially reverse the biological phenotype associated with SMIM25 expression in HCC cells (p < 0.05). Further transcriptome analysis in immunotherapy cohorts suggested the SMIM25-COX-2 axis might have predictive value for the response to immunotherapy. Our results suggest that SMIM25 may serve as a biomarker for the prognosis of HCC patients and may also be a predictive biomarker for the response to immunotherapy, enabling more precise and personalized HCC treatment.

Nanomaterials (NMs) have emerged as promising tools for disease diagnosis and therapy due to their unique physicochemical properties. To maximize the effectiveness and design of NMs-based medical applications, it is essential to comprehend the complex mechanisms of cellular uptake, subcellular localization, and cellular retention. This review illuminates the various pathways that NMs take to get from the extracellular environment to certain intracellular compartments by investigating the various mechanisms that underlie their interaction with cells. The cellular uptake of NMs involves complex interactions with cell membranes, encompassing endocytosis, phagocytosis, and other active transport mechanisms. Unique uptake patterns across cell types highlight the necessity for customized NMs designs. After internalization, NMs move through a variety of intracellular routes that affect where they are located subcellularly. Understanding these pathways is pivotal for enhancing the targeted delivery of therapeutic agents and imaging probes. Furthermore, the cellular retention of NMs plays a critical role in sustained therapeutic efficacy and long-term imaging capabilities. Factors influencing cellular retention include nanoparticle size, surface chemistry, and the cellular microenvironment. Strategies for prolonging cellular retention are discussed, including surface modifications and encapsulation techniques. In conclusion, a comprehensive understanding of the mechanisms governing cellular uptake, subcellular localization, and cellular retention of NMs is essential for advancing their application in disease diagnosis and therapy. This review provides insights into the intricate interplay between NMs and biological systems, offering a foundation for the rational design of next-generation nanomedicines.

为了提高课堂教学质量,作者教学团队在2018级109名临床本科生的"医学生物化学与分子生物学"教学中开展对分课堂.将每一知识单元的教学分为3个环节:首先教师讲授主体框架和重点难点;随后学生进行当堂自主学习;最后为课堂讨论阶段,学生进行分组讨论,教师给予及时反馈和总结.进行教学评价时,对分课堂模式教学得到绝大部分学生认可,提高了学生的学习主动性,能够培养团队合作精神和交流沟通技巧.

Background: Machine learning methods showed excellent predictive ability in a wide range of fields. For the survival of head and neck squamous cell carcinoma (HNSC), its multi-omics influence is crucial. This study attempts to establish a variety of machine learning multi-omics models to predict the survival of HNSC and find the most suitable machine learning prediction method. Methods: The HNSC clinical data and multi-omics data were downloaded from the TCGA database. The important variables were screened by the LASSO algorithm. We used a total of 12 supervised machine learning models to predict the outcome of HNSC survival and compared the results. In vitro qPCR was performed to verify core genes predicted by the random forest algorithm. Results: For omics of HNSC, the results of the twelve models showed that the performance of multi-omics was better than each single-omic alone. Results were presented, which showed that the Bayesian network(BN) model (area under the curve [AUC] 0.8250, F1 score=0.7917) and random forest(RF) model (area under the curve [AUC] 0.8002,F1 score=0.7839) played good prediction performance in HNSC multi-omics data. The results of in vitro qPCR were consistent with the RF algorithm. Conclusion: Machine learning methods could better forecast the survival outcome of HNSC. Meanwhile, this study found that the BN model and the RF model were the most superior. Moreover, the forecast result of multi-omics was better than single-omic alone in HNSC.

目的 乳腺癌是世界范围内最常见的恶性肿瘤之一.目前,人们对乳腺癌的发病机制进行了大量的研究,但对其分子机制的认识尚不清楚.本研究采用生物信息学技术,筛选乳腺癌潜在的关键基因,最终为乳腺癌的诊断、 治疗及预后判断提供潜在的生物标记物.方法 从基因表达综合数据库(GEO)下载基因芯片GSE36295、GSE71053和GSE86374,通过GEO2R鉴定差异表达基因(DEGs),并进行功能富集分析.利用STRING构建了蛋白质-蛋白质相互作用网络(PPI),并采用Cytoscape进行了模块分析.结果 共鉴定出95个DEGs,包括62个上调基因和33个下调基因.共鉴定出10个Hub基因:CENPF、KIF2C、TOP2A、NUSAP1、HMMR、MELK、KIF4A、ASPM、CEP55、CCNB1.结论 本研究发现的Hub基因可能对乳腺癌的发展和预后存在一定影响,为乳腺癌的诊断和治疗提供候选靶点.

马尔尼菲篮状菌(Talaromyces marneffei),旧称为马尔尼菲青霉菌(Penicillium marneffei),流行于东南亚和中国南部.法国Capponi等[1]在1956年从竹鼠体内分离的青霉菌属温控双相条件致病菌,室温25 ℃条件下表现为菌丝相, 37 ℃环境下表现为酵母相,酵母相菌体具有致病性.马尔尼菲篮状菌病主要集中于免疫力低下人群,尤其HIV患者,若得不到有效的治疗,病死率极高[2,3].近年来,感染T.marneffei发病率上升趋势明显[4],其传播途径最常见是经呼吸道吸入T. marneffei孢子导致感染.T.marneffei属胞内寄生真菌,其宿主细胞主要为巨噬细胞,易侵犯免疫系统受损患者的单核-巨噬细胞系统,但机体对其免疫机制尚不明确.本文就巨噬细胞对T. marneffei的识别机制,巨噬细胞抗T.marnef-fei机制及T.marneffei在巨噬细胞内的存活机制进行总结如下.

Talaromyces marneffei (TM) is an important opportunistic pathogenic fungus capable of causing disseminated lethal infection. In our previous study, we identified host lncRNAs and mRNAs that are dysregulated in TM-infected bronchial epithelial cells. In this report, we verified that IL-6, a key factor in acute inflammatory response, is down-regulated in TM pathogenesis. To elucidate the mechanism of IL-6 regulation, we analyzed the coding/non-coding network, and identified lncSSBP1, a novel lncRNA that is up-regulated by TM. Our results demonstrate that overexpression of lncSSBP1 decreases IL-6 mRNA expression, whereas knockdown of lncSSBP1 enhances IL-6 mRNA expression. Though lncSSBP1 is primarily localized to the nucleus, bioinformatics analysis suggests that it is unlikely to function as competing endogenous RNA or to interact with IL-6 transcription factors. Instead, RNA pull down and RNA immunoprecipitation assays showed that lncSSBP1 binds specifically to heterogenous nuclear ribonucleoprotein K (hnRNPK), which is involved in IL-6 mRNA processing. Our findings suggest that lncSSBP1 may affect IL-6 mRNA expression during TM infection through interaction with hnRNPk in bronchial epithelial cells. Our results suggest a novel pathway by which TM may suppress the immune response to its advantage.

数以万亿计的微生物生活在人类肠道中,形成了一个复杂的微生态群落.肠道微生物可为宿主提供营养和能量,并与人类疾病的发生发展密切相关.随着研究的不断深入,越来越多的证据表明肠道微生物的改变可引起性激素水平变化,进而导致一系列相关的疾病发生.本文就肠道微生物与多囊卵巢综合征、乳腺癌、卵巢癌等性激素相关疾病之间的关系进行阐述,旨在为人类疾病诊疗提供新思路.

Talaromyces marneffei (T. marneffei) is a medically important opportunistic dimorphic fungus that infects both humans and bamboo rats. However, the mechanisms of transmission and pathogenicity of T. marneffei are poorly understood. In our study, we combined Illumina and PacBio sequencing technologies to sequence and assemble a complete genome of T. marneffei. To elucidate the transmission route and source, we sequenced three additional T. marneffei isolates using Illumina sequencing technology. Variations among isolates were used to develop a multilocus sequence typing (MLST) system comprising five housekeeping genes that can be used to discriminate between isolates derived from different sources. Our analysis revealed that human and bamboo rat share identical genotypes in these five loci. Thus, we hypothesized that T. marneffei is transmitted to humans through inhalation of spores in the surrounding environment into the lungs and that the bamboo rat can serve as an important natural reservoir for pathogens. Furthermore, we also identified temperature-dependent polyketide synthases, non-ribosomal peptide synthetases and secreted proteins as putative pathogenicity-related factors. In addition, we identified antifungal drug targets that can be investigated in future studies to elucidate the mechanisms underlying drug resistance. In summary, our study presents the basic features of the T. marneffei genome and provides insights into the transmission and pathogenicity of T. marneffei, which warrant fundamental experimental research.

目的:分析利用实时定量PCR检测的方法检测胰岛素和高糖对巨噬细胞ACAT-1表达的影响.方法:将胰岛素和高糖共同作用于巨噬细胞A C A T-1,但是每次的时间不相同,分别为0小时、6小时、12小时、24小时及48小时,然后用实时定量PC R的方法进行检测,观察其产生的影响.结果:胰岛素和高糖共同作用于巨噬细胞ACAT-1不同的时间,12小时后的表达量要显著高于0、6、24及48小时的表达量(P<0.05);而48小时的表达量和0小时的表达量相比,无显著差异(P>0.05).结论:胰岛素和高糖共同作用于巨噬细胞ACAT-1将在12小时达到高峰,然后再逐渐下降,在48小时下降到0小时的水平.

生物化学是医学院校中一门重要的基础课程.随着我国教育改革的发展,对该课程的教学提出了新的要求,针对这些要求,文章从教学对象、教学目标、教学内容、教学方法等方面进行了总结与反思,以此提高教学能力,改善教学效果来适应当前教育教学改革的发展.

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of mortality.Our previous study shows the expression of calponin 2 (CNN2) is up-regulated in hepatocellular carcinoma tissues, especially in metastatic ones.To better understand the role of CNN2 in HCC, RNA interference (RNAi) was used to explore its role in tumor growth and metastasis.Methods: Lentivirus-mediated CNN2-shRNA was transfected into SK-hep-1 cells, and the efficacy of CNN2 expression, cell migration, invasion, proliferation and cell cycles were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), Transwell assay, methyl thiazol tetrazolium assay and flow cytometry, respectively.SK-hep-1 cells transfected with Lentivirus-CNN2 shRNA were xenografted in Balb/C nude mice to explore the effect of CNN2-shRNA in tumor growth.Xenograft tumor tissues were examined for their histopathology, cell apoptosis, the expression of total protein and their corresponding phosphorylated protein of MEK1/2, ERK1/2, AKT, by hematoxylin and eosin stain (H & E staining), TUNEL assay, immunohistochemical technique, respectively.Results: Our research shows it is evident that CNN2 shRNA can effectively down-regulate the expressions of CNN2 mRNA and protein, inhibit cell proliferations, arrest cell cycles at the S phase and reduce cell migration and invasion.SK-hep-1 cells with CNN2 down-regulation have markedly attenuated tumor growth in nude mice.Xenograft tumor tissues have displayed typical tumor characteristics and no apoptosis is detected in shRNA group or in control group.No metastatic tumor was found in any group of nude mice.With CNN2 protein down-regulation, the protein of pMEK1/2 and pERK1/2 are effectively down-regulated, except pAKT, AKT, MEK1/2 and ERK1/2.Conclusions: CNN2 plays an important role in tumor growth and metastasis, possibly through MEK1/2-ERK1/2 signaling pathway.Our study illustrate that CNN2 might be a potential target in HCC molecular target therapy.

衰老是一个非常复杂的过程,与细胞和组织中累积的各种大分子(DNA、蛋白质和脂质)损伤密不可分,并且是由细胞中不同的信号通道共同调控的结果,而雷帕霉素靶标途径就是其中的一种.该途径整合了各种来自细胞内外的信号以调控细胞的生长、增殖和代谢.越来越多证据表明,雷帕霉素靶蛋白(target of rapamycin,TOR)控制着细胞和组织老化的速度,影响着整个机体衰老过程.另外TOR参与调控自噬的发生,而自噬能使生物大分子和细胞器降解并回收重复利用.多种生物模型研究发现,衰老其实是与自噬的不足有关联.本文对TOR和自噬在衰老过程中的作用和相互关系进行综述,为发展与老年疾病相关的新型治疗方法提供思路.

虚拟实验教学是现代生物化学实验教学的有效补充,也是现代实验教育改革发展的前沿.文章着重介绍了广西医科大学生物化学与分子生物学教研室教师设计的虚拟软件、构建虚实结合的实验教学体系、引导学生充分利用虚拟软件进行自主学习、指导大学生利用虚拟实验训练辅助课外创新科研课题的开展和提高教师业务水平等具体的改革实践.最后,文章也对虚实结合实验教学实践中的不足进行了思考与总结.

在"互联网+"时代背景下,根据医学院校中医学神经生物学的学科特点和发展需求,本文提出"互联网+"医学神经生物学多元化的教学新模式,尝试以多元化教学模式为主,把数字化教学、微课教学、MOOC教学以及PBL教学等多种教学方法有机地结合起来,针对不同的教学阶段使用最合适的教学方法,在提升教学娱乐性和有效性的同时,充分调动学生们的主观能动性,更有效地巩固理论知识、强化记忆、培养科研思路,进而达到加强医学神经生物学课程建设、提升教学质量的效果,以更好地促进基础生物医学科研教育的发展和人才培养工作.

Talaromyces marneffei is an important opportunistic pathogenic fungus capable of causing systemic lethal infection through inhalation of its conidia. However, little is known about the pathogenesis and interactions between Talaromyces marneffei and host. The aim of this study was to identify potential long noncoding RNAs (lncRNAs) and coding genes associated with interactions between airway epithelial cell and Talaromyces marneffei conidia. We carried out a microarray analysis to determine the expression profile of lncRNA and mRNA in human bronchial epithelial cell in response to Talaromyces marneffei infection. Compared to control group, we found that 370 and 149 lncRNAs were up and down regulated, respectively. Meanwhile, the expression level of 269 and 60 mRNAs was increased and decreased, respectively. To understand the potential role of the differentially expressed lncRNAs, we performed functional annotations of the corresponding coding genes using gene ontology and pathway analyses. Our results provide insights into the pathogenesis of early infection by Talaromyces marneffei.

Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection.

The Chinese tree shrew (Tupaia belangeri yaoshanensis) has long been proposed to serve as an animal model for studying human diseases. However, its overall genetic diversity and population structure remain largely unknown. In the present study, we investigated the genetic diversity of population microsatellite DNA in wild Tupaia belangeri yaoshanensis. Sixteen microsatellite loci were assessed in 76 wild Tupaia belangeri yaoshanensis. The target microsatellite DNA fragments were amplified from the peripheral blood DNA of the animals by polymerase chain reaction (PCR), and the PCR-amplified products were verified by DNA sequencing and used for the analysis of allele, effective allele, genetic heterozygosity, polymorphism and population structure. Our results showed that of the 16 microsatellite loci examined, 5 microsatellite loci were monomorphic and 11 microsatellite loci were polymorphic. We detected 61 alleles in the polymorphic loci and found 2-10 (with an average of 5.5455) alleles per locus. Our data also showed that the observed and expected heterozygosities ranged from 0.087 to 0.8947 and 0.1368 to 0.7892 with an average of 0.3968 and 0.4796, respectively. Taken together, the results revealed a considerably high heterozygosity and high genetic diversity at the molecular level in the population of wild Tupaia belangeri yaoshanensis. The identified markers from the present study may be useful for individual identification and parentage testing, as well as for the quantification of population heterogeneity in the Chinese tree shrew.

马尔尼菲青霉菌是一种温度依赖性双相型条件致病真菌,可感染免疫缺陷人群,区域流行于东南亚地和我国南方,但其双相转换和致病性分子机制尚不清楚.实时荧光定量PCR是马尔尼菲青霉菌双相转换和致病性分子机制研究的重要手段,但仍缺乏用于马尔尼菲青霉菌实时荧光定量PCR标准化分析理想的内参基因.本研究根据转录组测序数据筛选了四个表达最稳定的Pfp、Rp123、FacpA、DigA基因与传统的内参基因18 SrRNA、β-aetin(Act1)β-tubulin(Btu)作为候选内参基因,用BestKeeper和geNorm软件进行基因表达稳定性分析.结果表明FacpA和DigA基因在马尔尼菲青霉菌双相转换过程中表达最为稳定,可作为用于马尔尼菲青霉菌实时荧光定量PCR标准化分析的内参基因.