BIOLOGY DIRECT 作为开放获取、同行评审的在线期刊服务于生命科学研究社区，为作者和读者提供了传统同行评审模式的替代方案。 BIOLOGY DIRECT 考虑目前被认为最有利于开放审查方法的学科领域的原创研究文章、假设、评论、发现笔记和评论，主要是那些具有重要非实验成分的领域。

Biology Direct is an open-access, peer-reviewed online journal that serves the life sciences research community. It provides authors and readers with an alternative to the traditional peer review model. Biology Direct considers original research articles, hypotheses, reviews, discovery notes, and commentaries, particularly in fields that are currently viewed as most conducive to open review methods.

《Biology Direct》是一份开放获取、同行评审的在线期刊，旨在服务于生命科学研究社区。它为作者和读者提供了一种传统同行评审模式的替代方案。《Biology Direct》接受原创研究文章、假设、评论、发现笔记和评论，特别关注那些具有重要非实验成分的学科领域。

Biology Direct

High-throughput sequencing is generating massive amounts of data at a pace that largely exceeds the throughput of data analysis routines. Here we introduce Fish the ChIPs (FC), a computational pipeline aimed at a broad public of users and designed to perform complete ChIP-Seq data analysis of an unlimited number of samples, thus increasing throughput, reproducibility and saving time. Starting from short read sequences, FC performs the following steps: 1) quality controls, 2) alignment to a reference genome, 3) peak calling, 4) genomic annotation, 5) generation of raw signal tracks for visualization on the UCSC and IGV genome browsers. FC exploits some of the fastest and most effective tools today available. Installation on a Mac platform requires very basic computational skills while configuration and usage are supported by a user-friendly graphic user interface. Alternatively, FC can be compiled from the source code on any Unix machine and then run with the possibility of customizing each single parameter through a simple configuration text file that can be generated using a dedicated user-friendly web-form. Considering the execution time, FC can be run on a desktop machine, even though the use of a computer cluster is recommended for analyses of large batches of data. FC is perfectly suited to work with data coming from Illumina Solexa Genome Analyzers or ABI SOLiD and its usage can potentially be extended to any sequencing platform. Compared to existing tools, FC has two main advantages that make it suitable for a broad range of users. First of all, it can be installed and run by wet biologists on a Mac machine. Besides it can handle an unlimited number of samples, being convenient for large analyses. In this context, computational biologists can increase reproducibility of their ChIP-Seq data analyses while saving time for downstream analyses. This article was reviewed by Gavin Huttley, George Shpakovski and Sarah Teichmann.

Iros Barozzi

Alberto Termanini

Saverio Minucci

Gioacchino Natoli

Fish the ChIPs: a pipeline for automated genomic annotation of ChIP-Seq data

Tumor Mutational Burden (TMB) have emerged as pivotal predictive biomarkers in determining prognosis and response to immunotherapy in colorectal cancer (CRC) patients. While Whole Exome Sequencing (WES) stands as the gold standard for TMB assessment, carry substantial costs and demand considerable time commitments. Additionally, the heterogeneity among high-TMB patients remains poorly characterized.

Yangyang Fang

Tianmei Fu

Qian Zhang

Ziqing Xiong

Kuai Yu

Aiping Le

Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer

机器学习驱动的突变负荷估计突显DNAH5作为结直肠癌的预后标志物

Breast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway.

Jiayi Sun

Jinquan Liu

Yudong Hou

Jianheng Bao

Teng Wang

Longbi Liu

Yidan Zhang

Rui Zhong

Zhenxuan Sun

Yan Ye

Jintao Liu

ZFP64 drives glycolysis-mediated stem cell-like properties and tumorigenesis in breast cancer

ZFP64驱动糖酵解介导的干细胞样特性和乳腺癌的肿瘤发生

Abstract Background RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of the m6A reader YTH domain family 2 (YTHDF2) has not been reported in anaplastic thyroid cancer (ATC) and its biological mechanism is unclear. Methods The relationship between YTHDF2 expression and ATC was determined using data sets and tissue samples. A range of analytical techniques were employed to investigate the regulatory mechanism of YTHDF2 in ATC, including bioinformatics analysis, m6A dot-blot analysis, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, RNA sequencing, RNA stability assays and dual luciferase reporter gene assays. In vitro and in vivo assays were also conducted to determine the contribution of YTHDF2 to ATC development. Results YTHDF2 expression was significantly increased in ATC. The comprehensive in vitro and in vivo experiments demonstrated that YTHDF2 knockdown significantly attenuated ATC proliferation, invasion, migration, and apoptosis promotion, whereas YTHDF2 overexpression yielded the opposite trend. Mechanistically, RNA-seq, MeRIP-seq and RIP-seq analysis, and molecular biology experiments demonstrated that YTHDF2 accelerated the degradation of DNA damage-inducible transcript 4 or regulated in DNA damage and development 1 (DDIT4, or REDD1) mRNA in an m6A-dependent manner, which in turn activated the AKT/mTOR signaling pathway and induced activation of epithelial-mesenchymal transition (EMT), thereby promoting ATC tumor progression. Conclusions This study is the first to demonstrate that elevated YTHDF2 expression levels suppress DDIT4 expression in an m6A-dependent manner and activate the AKT/mTOR signaling pathway, thereby promoting ATC progression. YTHDF2 plays a pivotal role in ATC progression, and it may serve as a promising therapeutic target in the future.

Bao Dai

Lei Xu

Shikuo Rong

Muye Song

Ziteng Lan

Weijian Chen

Lingyun Zhang

Yongchen Liu

Linhe Wang

Jinghua Li

Jian Chen

Zeyu Wu

YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway

YTHDF2通过激活DDIT4/AKT/mTOR信号通路促进甲状腺未分化癌进展

Prior research has highlighted the involvement of a transcriptional complex comprising C-terminal binding protein 2 (CtBP2), histone acetyltransferase p300, and nuclear factor kappa B (NF-κB) in the transactivation of proinflammatory cytokine genes, contributing to inflammation in mice with acute respiratory distress syndrome (ARDS). Nonetheless, it remains uncertain whether the therapeutic targeting of the CtBP2-p300-NF-κB complex holds potential for ARDS suppression.

Fan Li

Wenqing Yan

Weihua Dong

Zhiping Chen

Zhi Chen

PNSC928, a plant-derived compound, specifically disrupts CtBP2-p300 interaction and reduces inflammation in mice with acute respiratory distress syndrome

PNSC928，一种植物来源的化合物，特异性破坏CtBP2-p300相互作用并减轻小鼠急性呼吸窘迫综合征中的炎症

MicroRNAs (miRNAs) have shown potential as diagnostic biomarkers for myocardial infarction (MI) due to their early dysregulation and stability in circulation after MI. Moreover, they play a crucial role in regulating adaptive and maladaptive responses in cardiovascular diseases, making them attractive targets for potential biomarkers. However, their potential as novel biomarkers for diagnosing cardiovascular diseases requires systematic evaluation.

Mehrdad Samadishadlou

Reza Rahbarghazi

Kaveh Kavousi

Farhad Bani

An exploration into the diagnostic capabilities of microRNAs for myocardial infarction using machine learning

利用机器学习探索微小RNAs对心肌梗死的诊断能力

Extrachromosomal circular DNAs (eccDNAs) are commonly found in various tumors and play a critical role in promoting oncogenesis. However, little is known about the characteristics and nature of eccDNAs in human heart failure. The aim of this study was to comprehensively analyze eccDNAs in human heart failure caused by dilated cardiomyopathy (DCM) and explore their potential functions. Circle-Seq and RNA-Seq were performed in cardiac tissue samples obtained from patients with DCM and healthy controls to identify eccDNAs and corresponding genes. Inward PCR, outward PCR and Sanger sequencing were conducted to validate the circular structure of eccDNAs. Bioinformatics was employed to probe the transcriptional activity of eccDNAs and their potential roles in the development of DCM. Ligase assisted minicircle accumulation strategy was used to synthesize a 500 bp circular DNA with a random sequence. EccDNAs originated from all chromosomes, with the majority being less than 1 kb in size and about half containing genes or gene fragments. They were derived from specific repeat elements and primarily mapped to 5′UTR, 3′UTR, and CpG islands. Gene-rich chromosomes 17 and 19 exhibited higher eccDNA enrichment. Sequence motifs flanking eccDNA junction sites displayed frequent nucleotide repeats. The circular structure of eccDNAs were confirmed. Integration of Circle-Seq and RNA-Seq data identified that large eccDNAs can be directly transcribed in non-dividing cardiomyocytes, indicating their potential roles in gene expression. Small circular DNA elicited a stronger cytokine response than linear DNA with the same sequence. Our work provided a detailed profiling of eccDNAs in both healthy and DCM hearts and demonstrated the potential functions of both large and small eccDNAs. These findings enhance the comprehension of the role of eccDNAs in cardiac pathophysiology and establish a theoretical foundation for future investigations on eccDNAs in DCM.

Zhenhao Lin

Fangjie Dai

Bo Li

Yongchao Zhao

Changqian Wang

Integrating Circle-Seq with transcriptomics reveals genome-wide characterization of extrachromosomal circular DNA for dilated cardiomyopathy

整合Circle-Seq与转录组学揭示扩张型心肌病的全基因组外染色体环状DNA特征

Abstract Background Mitochondria are highly dynamic organelles that constantly undergo processes of fission and fusion. The changes in mitochondrial dynamics shape the organellar morphology and influence cellular activity regulation. Soft X-ray tomography (SXT) allows for three-dimensional imaging of cellular structures while they remain in their natural, hydrated state, which omits the need for cell fixation and sectioning. Synchrotron facilities globally primarily use flat grids as sample carriers for SXT analysis, focusing on adherent cells. To investigate mitochondrial morphology and structure in hydrated yeast cells using SXT, it is necessary to establish a method that employs the flat grid system for examining cells in suspension. Results We developed a procedure to adhere suspended yeast cells to a flat grid for SXT analysis. Using this protocol, we obtained images of wild-type yeast cells, strains with mitochondrial dynamics defects, and mutant cells possessing distinctive mitochondria. The SXT images align well with the results from fluorescent microscopy. Optimized organellar visualization was achieved by constructing three-dimensional models of entire yeast cells. Conclusions In this study, we characterized the mitochondrial network in yeast cells using SXT. The optimized sample preparation procedure was effective for suspended cells like yeast, utilizing a flat grid system to analyze mitochondrial structure through SXT. The findings corresponded with the mitochondrial morphology observed under fluorescence microscopy, both in regular and disrupted dynamic equilibrium. With the acquired image of unique mitochondria in Δhap2 cells, our results revealed that intricate details of organelles, such as mitochondria and vacuoles in yeast cells, can be characterized using SXT. Therefore, this optimized system supports the expanded application of SXT for studying organellar structure and morphology in suspended cells.

Wei-Ling Huang

Chang-Lin Chen

Zi-Jing Lin

Chia-Chun Hsieh

Mo Da-Sang Hua

Chih-Chan Cheng

Tzu-Hao Cheng

Lee-Jene Lai

Chuang-Rung Chang

Soft X-ray tomography analysis of mitochondria dynamics in Saccharomyces cerevisiae

酿酒酵母线粒体动力学的软X射线断层扫描分析

Here, we investigated the potential interaction between bromodomain-containing protein 4 (BRD4), an established epigenetic modulator and transcriptional coactivator, and p63, a member of the p53 transcription factor family, essential for epithelial development and skin homeostasis. Our protein–protein interaction assays demonstrated a strong and conserved physical interaction between BRD4 and the p53 family members—p63, p73, and p53—suggesting a shared binding region among these proteins. While the role of BRD4 in cancer development through its interaction with p53 has been explored, the effects of BRD4 and Bromodomain and Extra Terminal (BET) inhibitors in non-transformed cells, such as keratinocytes, remain largely unknown. Our functional analyses revealed changes in cellular proliferation and differentiation in keratinocytes depleted of either p63 or BRD4, which were further supported by using the BRD4 inhibitor JQ1. Transcriptomic analyses, chromatin immunoprecipitation, and RT-qPCR indicated a synergistic mechanism between p63 and BRD4 in regulating the transcription of keratinocyte-specific p63 target genes, including HK2, FOXM1, and EVPL. This study not only highlights the complex relationship between BRD4 and p53 family members but also suggests a role for BRD4 in maintaining keratinocyte functions. Our findings pave the way for further exploration of potential therapeutic applications of BRD4 inhibitors in treating skin disorders.

E. Foffi

A. Violante

R. Pecorari

A. M. Lena

F. Rugolo

G. Melino

E. Candi

BRD4 sustains p63 transcriptional program in keratinocytes

BRD4维持角质形成细胞中p63的转录程序

Osteoporosis, a metabolic disorder, remains challenging to treat due to limited understanding of its underlying mechanism. The annual cycle of "cyclic physiological osteoporosis (CPO)" and its full reversal in male deer represents a unique natural model for studying this condition. Deer antlers, weighing up to 25 kg/pair, derive over 60% of their mineral contents from deer skeleton during mineralization. Based on the literature, we propose to divide CPO and its reversal into two phases: Phase I (approximately 115 days): from hard antler casting to the end of antler linear growth, marked by simultaneous robust antler ossification and CPO development; and Phase II (up to 165 days): from end of Phase I to the onset of antler skin shedding, characterized by complete antler mineralization and CPO reversal. This review analyzes the paradoxical occurrence of robust antler ossification and skeleton CPO within the same endocrine microenvironment during phase I; total antler mineralization and full reversal of deer skeleton CPO in phase II. Furthermore, we will discuss potential insights for osteoporosis treatment using deer materials from the period of Phase II. Our goal is to identify novel substances and therapies that could be applied in clinical setting to effectively treat osteoporosis.

Chunyi Li

Wenying Wang

Guokun Zhang

Hengxing Ba

He Liu

Jincheng Wang

Wei Li

Gerry Melino

Yufang Shi

Bone metabolism associated with annual antler regeneration: a deer insight into osteoporosis reversal

与鹿角年再生相关的骨代谢：逆转骨质疏松症的启示

Abbreviation	Biol Direct
Journal Impact	5.51
Quartiles(Global)	BIOLOGY(Q1)

ISSN	1745-6150
h-index	81

Publication Information	Publisher: BioMed Central Ltd，Publishing cycle: Irregular，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2006，Proportion of original research papers: 82.93%，Self Citation Rate:8.80%， Gold OA Rate: 98.65%
Journal Fees	$2790Details
Average review cycle	网友分享经验：平均7月
Average recruitment ratio	网友分享经验：约85%

Biology Direct

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