GENES (ISSN 2073-4425) 是一本经过同行评审的国际开放获取期刊，为与基因、遗传学和基因组学相关的研究提供了一个高级论坛。它发表评论、研究文章、通讯和技术说明。论文的长度没有限制，我们鼓励科学家尽可能详细地发表他们的结果。

GENES (ISSN 2073-4425) is a peer-reviewed international open-access journal that provides a high-level forum for research related to genes, genetics, and genomics. It publishes comments, research articles, communications, and technical notes. There is no restriction on the length of papers, and we encourage scientists to present their results as comprehensively as possible.

《Genes》（ISSN 2073-4425）是一本经过同行评审的国际开放获取期刊，专注于基因、遗传学和基因组学相关研究。期刊为研究者提供了一个高级论坛，发表内容包括评论、研究文章、通讯和技术说明。论文长度没有限制，我们鼓励科学家尽可能详细地分享他们的研究成果。

Genes

The production of around 2.5 million red blood cells (RBCs) per second in erythropoiesis is one of the most intense activities in the body. It continuously consumes large amounts of iron, approximately 80% of which is recycled from aged erythrocytes. Therefore, similar to the “making”, the “breaking” of red blood cells is also very rapid and represents one of the key processes in mammalian physiology. Under steady-state conditions, this important task is accomplished by specialized macrophages, mostly liver Kupffer cells (KCs) and splenic red pulp macrophages (RPMs). It relies to a large extent on the engulfment of red blood cells via so-called erythrophagocytosis. Surprisingly, we still understand little about the mechanistic details of the removal and processing of red blood cells by these specialized macrophages. We have only started to uncover the signaling pathways that imprint their identity, control their functions and enable their plasticity. Recent findings also identify other myeloid cell types capable of red blood cell removal and establish reciprocal cross-talk between the intensity of erythrophagocytosis and other cellular activities. Here, we aimed to review the multiple and emerging facets of iron recycling to illustrate how this exciting field of study is currently expanding.

Patryk Slusarczyk

Katarzyna Mleczko-Sanecka

The Multiple Facets of Iron Recycling

Type-V-F Cas12f proteins, also known as Cas14, have drawn significant interest within the diverse CRISPR-Cas nucleases due to their compact size. This study involves analyzing and comparing Cas14-homology proteins in prokaryotic genomes through mining, sequence comparisons, a phylogenetic analysis, and an array/repeat analysis. In our analysis, we identified and mined a total of 93 Cas14-homology proteins that ranged in size from 344 aa to 843 aa. The majority of the Cas14-homology proteins discovered in this analysis were found within the Firmicutes group, which contained 37 species, representing 42% of all the Cas14-homology proteins identified. In archaea, the DPANN group had the highest number of species containing Cas14-homology proteins, a total of three species. The phylogenetic analysis results demonstrate the division of Cas14-homology proteins into three clades: Cas14-A, Cas14-B, and Cas14-U. Extensive similarity was observed at the C-terminal end (CTD) through a domain comparison of the three clades, suggesting a potentially shared mechanism of action due to the presence of cutting domains in that region. Additionally, a sequence similarity analysis of all the identified Cas14 sequences indicated a low level of similarity (18%) between the protein variants. The analysis of repeats/arrays in the extended nucleotide sequences of the identified Cas14-homology proteins highlighted that 44 out of the total mined proteins possessed CRISPR-associated repeats, with 20 of them being specific to Cas14. Our study contributes to the increased understanding of Cas14 proteins across prokaryotic genomes. These homologous proteins have the potential for future applications in the mining and engineering of Cas14 proteins.

Numan Ullah

Naisu Yang

Zhongxia Guan

Kuilin Xiang

Yali Wang

Mohamed Diaby

Cai Chen

Bo Gao

Chengyi Song

Comparative Analysis and Phylogenetic Insights of Cas14-Homology Proteins in Bacteria and Archaea

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are biologically active substances secreted by MSCs into the extracellular matrix that play an immunomodulatory role in skin damage repair. To investigate the mechanism of MSC-EVs in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and extracellular matrix remodeling during wound healing, we focused on the effects of EVs on multiple cell types at various stages of skin injury. A literature review was conducted to explore related research on the influence of MSC-EVs on the types of cells involved in wound healing. MSC-EVs show a strong regulatory ability on immune cells involved in the regulation of inflammation, including macrophages, neutrophils, and T cells, and other cells involved in tissue proliferation and remodeling, such as fibroblasts, keratinocytes, and endothelial cells, during wound healing in in vitro and in vivo experiments, which substantially promoted the understanding of wound healing in the field of trauma medicine. MSC-EVs have potential applications in combating poor skin wound healing. Elucidating the mechanism of action of EVs in the wound-healing process would greatly advance the understanding of therapeutic wound healing.

Weiyuan Zhang

Yang Ling

Yang Sun

Fengjun Xiao

Lisheng Wang

Extracellular Vesicles Derived from Mesenchymal Stem Cells Promote Wound Healing and Skin Regeneration by Modulating Multiple Cellular Changes: A Brief Review

Background: Type 1 pili, as an important virulence factor of E. coli, has certain homology between APEC and UPEC, but the homology degree is not clear enough. Objectives: This study aims to compare the homology between them. Methods: The recombinant bacteria were constructed by homologous recombination. The pili were observed by TEM, and the hemagglutination characteristics were determined by MHSA. The complete gene sequence was determined by sequencing, and the amino acid sequences of the functional proteins of type 1 pili of APEC and UPEC were compared. Results: TEM showed that they could express pili, which were slender, straight, and dense. Stable-pUC-fimBH has MHSA but stable-pUC-fimBG does not. The amino acid sequence similarity of FimB of NJ05 and UPEC was 98.8%, FimE was 99.4%, and the similarity between them was 51.5%. Compared with UPEC’s type 1 pili FimC and FimD sequences, the similarity was 99.52% and 87.8%, respectively. The amino acid sequence of FimA of NJ05 was 89–96%, similar to UPEC, and the N-terminal and C-terminal amino acid sequences were exactly the same. The gene sequence and amino acid sequence similarity of FimH between them were both above 99%. The similarity of the pilus binding domain of FimH was 52.8%, but only 27.6% in the receptor binding domain. A few of the same amino acid residues were found in the corresponding regions of FimA, FimF, FimG, and FimH. Conclusions: The type 1 pili of APEC and UPEC come from the same origin, which is helpful to further reveal the pathogenic mechanism of E. coli infection in the poultry respiratory tract.

Junhong Chen

Wei Dai

Hang Wang

Weiqiang Lei

Guangyuan Fang

Dingzhen Dai

Cloning and Expression of Pigeon-Derived Escherichia coli Type 1 Pilus Clusters and Analysis of Amino Acid Sequence Characteristics of Functional Proteins

鸽源大肠杆菌I型菌毛簇的克隆与表达及功能蛋白氨基酸序列特征分析

Although it has gained more attention in recent years, the relationship between breast cancer (BC) and mitochondrial oxidative phosphorylation (OXPHOS) is still not well understood. Importantly, Complex IV or Cytochrome C Oxidase (COX) of OXPHOS is one of the key players in mitochondrial balance. An in silico investigation of mutations in structural genes of Complex IV was conducted in BC, comprising 2107 samples. Our findings show four variants (rs267606614, rs753969142, rs199476128 and rs267606884) with significant pathogenic potential. Moreover, we highlight nine genes (MT-CO1, MT-CO2, MT-CO3, CO4I2, COX5A, COX5B, COX6A2, COX6C and COX7B2) with a potential impact on BC.

Ricardo Cunha de Oliveira

Sávio Pinho dos Reis

Giovanna C. Cavalcante

Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms.

Sabina Iluta

Madalina Nistor

Sanda Buruiana

Delia Dima

Wnt Signaling Pathway in Tumor Biology

Wnt信号通路在肿瘤生物学中的作用

Erectile dysfunction (ED) is a pathophysiological condition in which the patients cannot achieve an erection during sexual activity, and it is often overlooked yet prevalent among diabetic men, globally affecting approximately 35–75% of diabetic individuals. The precise mechanisms through which diabetes contributes to ED remain elusive, but the existing literature suggests the potential involvement of nerve and vascular damage that affects the penile supply. In the present review, we reanalyze the existing human single-cell transcriptomic data from patients having diabetes mellitus-associated ED with normal erections. The analysis validates the expression of genes associated with antioxidative pathways, growth factors, adipokines, angiogenesis, vascular functions, penile erection, sexual function, and inflammation in diverse cell types from healthy individuals and those with ED. Our transcriptomic analysis reveals alterations in the expression of adiponectin receptors in the pathogenesis of ED compared to their counterparts in healthy subjects. This comprehensive review sheds light on the molecular underpinnings of ED in the context of diabetes, providing an in-depth understanding of the biological and cellular alterations involved and paving the way for possible targeted therapeutic discoveries in the field of diabetes-associated male infertility.

Mahmuda Begum

Mayank Choubey

Munichandra Babu Tirumalasetty

Shahida Arbee

Sibly Sadik

Mohammad Mohabbulla Mohib

Shivani Srivastava

Naofel Minhaz

Riffat Alam

Mohammad Sarif Mohiuddin

Exploring the Molecular Link Between Diabetes and Erectile Dysfunction Through Single-Cell Transcriptome Analysis

通过单细胞转录组分析探索糖尿病与勃起功能障碍之间的分子联系

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype. However, it is not known whether changes in SCFA levels, especially acetate, occurred during the canalicular or early saccular phase among pregnant women whose children did not develop asthma. Methods: In this research, we investigated this question using plasma samples obtained from mothers during the 20th and 28th weeks of pregnancy. Mothers whose children developed asthma were categorized as cases, while those whose children did not were categorized as controls. The specimens were assayed for a panel of SCFAs consisting of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate. Results: The resulting data indicated no significant differences between the cases and controls, either at week 20 or week 28, in any of the SCFAs measured, despite the vascularization during these phases. Conclusions: We did not find differences in measured SCFAs at week 20 or at week 28. A larger prospective study covering multiple time points is necessary to confirm the findings of this preliminary study. Such a study, together with the published literature regarding later time points, may help discover critical windows during pregnancy when simple manipulation of diet will result in healthier outcomes for infants.

Huang Lin

Neil J. Perkins

Flory Nkoy

Joseph B. Stanford

Karen C. Schliep

Shyamal D. Peddada

A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma

胎儿肺发育管状期和囊状早期阶段短链脂肪酸与儿童哮喘的研究

Background: WFS1-spectrum disorders are caused by a mutation in the WFS1 gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in the WFS1 gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. Methods: The aim of this study was to evaluate genotype–phenotype correlations in Polish patients with WFS1-spectrum disorders. The study group constituted 22 patients (10 F; 12 M), including 10 patients (3 F; 7 M) referred to the Outpatient Clinic for Rare Diseases in Children and Adolescents and Diabetogenetics between 2019 and 2024 with clinical symptoms suggestive of WFS1-spectrum disorders, and 12 of their first-degree relatives (7 F; 5 M) from 10 families in Poland. Molecular testing was performed using tNGS (Targeted Next Generation Sequencing; Illumina) and analyzed for variants in the WFS1 gene. Results: Thirteen different variants in the WFS1 gene were found in 22 individuals (10 patients and family members), including the identification of two new variants (c.1535T&gt;C and c.2485C&gt;G). All patients had hyperglycemia or DM, hearing impairment, OA, or a combination of these symptoms. Four patients in the study group were diagnosed with Wolfram syndrome and all were compound heterozygotes for variants in the WFS1 gene. Conclusions: The evaluation of molecular characteristics in combination with clinical symptoms broadens the understanding of WFS1-spectrum disorders and allows more accurate management and prognosis for patients with this diagnosis.

Julia Grzybowska-Adamowicz

Karolina Gadzalska

Paulina Jakiel

Ewa Juścińska

Monika Gorządek

Sebastian Skoczylas

Tomasz Płoszaj

Przemysława Jarosz-Chobot

Irina Kowalska

Małgorzata Myśliwiec

Agnieszka Szadkowska

Agnieszka Zmysłowska

Patients with a Wide Range of Disorders Related to WFS1 Gene Variants: Novel Mutations and Genotype–Phenotype Correlations

与WFS1基因变异相关的一系列疾病患者：新突变及基因型-表型相关性

Background/Objectives: Understanding the relationship between DNA sequences and gene expression levels is of significant biological importance. Recent advancements have demonstrated the ability of deep learning to predict gene expression levels directly from genomic data. However, traditional methods are limited by basic word encoding techniques, which fail to capture the inherent features and patterns of DNA sequences. Methods: We introduce TExCNN, a novel framework that integrates the pre-trained models DNABERT and DNABERT-2 to generate word embeddings for DNA sequences. We partitioned the DNA sequences into manageable segments and computed their respective embeddings using the pre-trained models. These embeddings were then utilized as inputs to our deep learning framework, which was based on convolutional neural network. Results: TExCNN outperformed current state-of-the-art models, achieving an average R2 score of 0.622, compared to the 0.596 score achieved by the DeepLncLoc model, which is based on the Word2Vec model and a text convolutional neural network. Furthermore, when the sequence length was extended from 10,500 bp to 50,000 bp, TExCNN achieved an even higher average R2 score of 0.639. The prediction accuracy improved further when additional biological features were incorporated. Conclusions: Our experimental results demonstrate that the use of pre-trained models for word embedding generation significantly improves the accuracy of predicting gene expression. The proposed TExCNN pipeline performes optimally with longer DNA sequences and is adaptable for both cell-type-independent and cell-type-dependent predictions.

Guohao Dong

Yuqian Wu

Lan Huang

Fei Li

Fengfeng Zhou

TExCNN: Leveraging Pre-Trained Models to Predict Gene Expression from Genomic Sequences

TExCNN：利用预训练模型从基因组序列预测基因表达

Abbreviation
Journal Impact	2.85
Quartiles(Global)	GENETICS & HEREDITY(Q2)

Publication Information	Publisher: Multidisciplinary Digital Publishing Institute (MDPI)，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2010，Proportion of original research papers: 87.81%，Self Citation Rate:7.10%， Gold OA Rate: 99.68%
Average review cycle	期刊官网数据：平均22.94天网友分享经验：11 Weeks

Genes

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