bluuebunny/crossref_metadata_2025_split huggingface dataset:
The steroid hormone estriol (E3) regulates epigenetic programming of fetal mouse brain and reproductive tract
Authors: Zhou Yuping , Gu Baoxia , Brichant Geraldine , Singh Jay Prakash , Yang Huan , Chang Hao , Zhao Yanding , Cheng Chao , Liu Zhong-Wu , Alderman Myles H. , Lu Lingeng , Yang Xiaoyong , Gao Xiao-Bing , Taylor Hugh S. 
Published: May 2022

Abstract
Background
Estriol (E3) is a steroid hormone formed only during pregnancy in primates including humans. Although E3 is synthesized at large amounts through a complex pathway involving the fetus and placenta, it is not required for the maintenance of pregnancy and has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, estrogen exposure during pregnancy may have an effect on organs both within and outside the reproductive system, and compounds with binding affinity for estrogen receptors weaker than E3 have been found to impact reproductive organs and the brain. Here, we explore potential effects of E3 on fetal development using mouse as a model system.

Results
We administered E3 to pregnant mice, exposing the fetus to E3. Adult females exposed to E3 in utero (E3-mice) had increased fertility and superior pregnancy outcomes. Female and male E3-mice showed decreased anxiety and increased exploratory behavior. The expression levels and DNA methylation patterns of multiple genes in the uteri and brains of E3-mice were distinct from controls. E3 promoted complexing of estrogen receptors with several DNA/histone modifiers and their binding to target genes. E3 functions by driving epigenetic change, mediated through epigenetic modifier interactions with estrogen receptors rather than through canonical nuclear transcriptional activation.

Conclusions
We identify an unexpected functional role for E3 in fetal reproductive system and brain. We further identify a novel mechanism of estrogen action, through recruitment of epigenetic modifiers to estrogen receptors and their target genes, which is not correlated with the traditional view of estrogen potency.
Associations of face-to-face and non-face-to-face social isolation with all-cause and cause-specific mortality: 13-year follow-up of the Guangzhou Biobank Cohort study
Authors: Wang Jiao , Zhang Wei Sen , Jiang Chao Qiang , Zhu Feng , Jin Ya Li , Cheng Kar Keung , Lam Tai Hing , Xu Lin 
Published: May 2022

Abstract
Background
Although social isolation has been associated with a higher mortality risk, little is known about the potential different impacts of face-to-face and non-face-to-face isolation on mortality. We examined the prospective associations of four types of social isolation, including face-to-face isolation with co-inhabitants and non-co-inhabitants, non-face-to-face isolation, and club/organization isolation, with all-cause and cause-specific mortality separately.

Methods
This prospective cohort study included 30,430 adults in Guangzhou Biobank Cohort Study (GBCS), who were recruited during 2003–2008 and followed up till Dec 2019.

Results
During an average of 13.2 years of follow-up, 4933 deaths occurred during 396,466 person-years. Participants who lived alone had higher risks of all-cause (adjusted hazard ratio (AHR) 1.24; 95% confidence interval (CI) 1.04-1.49) and cardiovascular disease (CVD) (1.61; 1.20–2.03) mortality than those who had ≥ 3 co-habitant contact after adjustment for thirteen potential confounders. Compared with those who had ≥ 1 time/month non-co-inhabitant contact, those without such contact had higher risks of all-cause (1.60; 1.20–2.00) and CVD (1.91; 1.20–2.62) mortality. The corresponding AHR (95% CI) in participants without telephone/mail contact were 1.27 (1.14–1.42) for all-cause, 1.30 (1.08–1.56) for CVD, and 1.37 (1.12–1.67) for other-cause mortality. However, no association of club/organization contact with the above mortality and no association of all four types of isolation with cancer mortality were found.

Conclusions
In this cohort study, face-to-face and non-face-to-face isolation were both positively associated with all-cause, CVD-, and other-cause (but not cancer) mortality. Our finding suggests a need to promote non-face-to-face contact among middle-aged and older adults.
Prevalence and molecular characterization of Dirofilaria immitis in road killed canids of northern Iran
Authors: Sharifdini Meysam , Karimi Mahan , Ashrafi Keyhan , Soleimani Mostafa , Mirjalali Hamed 
Published: May 2022

AbstractBackgroundDirofilaria immitisis a mosquito-borne filarial nematode, which infects primarily wild and domestic canids, causing cardiopulmonary dirofilariasis. The aim of the present study was to determine the prevalence and characterize molecular features ofD. immitisin road killed canids, northern Iran.MethodsThe carcasses of 53 road killed canids including 18 dogs (Canis familiaris), and 35 golden jackals (C. aureus) were necropsied in both Mazanderan and Guilan provinces, northern Iran. The molecular analyses were conducted based on the cytochrome oxidase (Cox) 1 and 18S ribosomal RNA (rRNA) genes.ResultsThe heartworm infection was found in 55.6% of dogs and 22.9% of jackals. Our study revealed significantly higher prevalence ofD. immitisin dogs compared to jackals (P = 0.031). The prevalence ofD. immitiswas no statistically significant between males and females in both dogs and jackal (P > 0.05). Comparison of theCox1 gene sequences with available data in the GenBank illustrated 100% similarity withD. immitisisolates from different hosts in European, Asian, and South American continents. Moreover, the 18S rRNA gene sequences showed 100% identity with dog isolates from Japan and French Guiana.ConclusionsThis study confirms the high prevalence ofD. immitisin dogs and jackals of northern Iran. Developing control programs to prevent transmission of the disease is necessary for dogs and humans in the study areas.
Stratification of lncRNA modulation networks in breast cancer
Authors: Yu Wen-Hsuan , Hsu Chia-Lang , Lin Chen-Ching , Oyang Yen-Jen , Juan Hsueh-Fen , Huang Hsuan-Cheng 
Published: May 2022

Abstract
Background
Recently, non-coding RNAs are of growing interest, and more scientists attach importance to research on their functions. Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts longer than 200 nucleotides. We already knew that lncRNAs are related to cancers and will be dysregulated in them. But most of their functions are still left to further study. A mechanism of RNA regulation, known as competing endogenous RNAs (ceRNAs), has been proposed to explain the complex relationships among mRNAs and lncRNAs by competing for binding with shared microRNAs (miRNAs).

Methods
We proposed an analysis framework to construct the association networks among lncRNA, mRNA, and miRNAs based on their expression patterns and decipher their network modules.

Results
We collected a large-scale gene expression dataset of 1,061 samples from breast invasive carcinoma (BRCA) patients, each consisted of the expression profiles of 4,359 lncRNAs, 16,517 mRNAs, and 534 miRNAs, and applied the proposed analysis approach to interrogate them. We have uncovered the underlying ceRNA modules and the key modulatory lncRNAs for different subtypes of breast cancer.

Conclusions
We proposed a modulatory analysis to infer the ceRNA effects among mRNAs and lncRNAs and performed functional analysis to reveal the plausible mechanisms of lncRNA modulation in the four breast cancer subtypes. Our results might provide new directions for breast cancer therapeutics and the proposed method could be readily applied to other diseases.
A systematic analysis of gene–gene interaction in multiple sclerosis
Authors: Slim Lotfi , Chatelain Clément , Foucauld Hélène de , Azencott Chloé-Agathe 
Published: May 2022

Abstract
Background
For the most part, genome-wide association studies (GWAS) have only partially explained the heritability of complex diseases. One of their limitations is to assume independent contributions of individual variants to the phenotype. Many tools have therefore been developed to investigate the interactions between distant loci, or epistasis. Among them, the recently proposed EpiGWAS models the interactions between a target variant and the rest of the genome. However, applying this approach to studying interactions along all genes of a disease map is not straightforward. Here, we propose a pipeline to that effect, which we illustrate by investigating a multiple sclerosis GWAS dataset from the Wellcome Trust Case Control Consortium 2 through 19 disease maps from the MetaCore pathway database.

Results
For each disease map, we build an epistatic network by connecting the genes that are deemed to interact. These networks tend to be connected, complementary to the disease maps and contain hubs. In addition, we report 4 epistatic gene pairs involving missense variants, and 25 gene pairs with a deleterious epistatic effect mediated by eQTLs. Among these, we highlight the interaction of GLI-1 and SUFU, and of IP10 and NF-$$\kappa$$
κ
B, as they both match known biological interactions. The latter pair is particularly promising for therapeutic development, as both genes have known inhibitors.

Conclusions
Our study showcases the ability of EpiGWAS to uncover biologically interpretable epistatic interactions that are potentially actionable for the development of combination therapy.
Systematic analysis of prognostic significance, functional enrichment and immune implication of STK10 in acute myeloid leukemia
Authors: Bi Lei , Jia Shuangshuang , Hu Wuyue , Su Xiaoli , Chen Xiequn , Tang Hailong 
Published: May 2022

Abstract
Background
Despite deeper understanding of the genetic landscape of acute myeloid leukemia (AML), the improvement of survival is still a great challenge. STK10 is overexpressed in several cancers with functions varying according to cancer types. But the functions of STK10 in AML has never been reported.

Methods
We analyzed the expression, prognosis and potential functions of STK10 utilizing public web servers. Metascape and the String database were used for functional and protein–protein interaction analyses.

Results
We found STK10 was enriched in blood & immune cells and overexpressed in AML. High STK10 expression was associated with poor overall survival, which was also identified in the subgroups of patients ≤ 60 years old and patients with non-high-risk cytogenetics. We demonstrated genes associated with STK10 were enriched in blood, spleen and bone marrow, influencing the immune function and biological process of AML. ITGB2 and ITGAM might directly interact with STK10 and were associated with poor prognosis. Besides, STK10 was associated with the infiltration of immune cells and immune checkpoints, like HLA-E, CD274 and GAL-9.

Conclusions
The present study was the original description of STK10 in AML and set the stage for developing STK10 as a new prognostic marker or therapeutic target for AML.
Melanin biopolymer synthesis using a new melanogenic strain of Flavobacterium kingsejongi and a recombinant strain of Escherichia coli expressing 4-hydroxyphenylpyruvate dioxygenase from F. kingsejongi
Authors: Lee Han Sae , Choi Jun Young , Kwon Soon Jae , Park Eun Seo , Oh Byeong M. , Kim Jong H. , Lee Pyung Cheon 
Published: May 2022

Abstract
Background
Melanins are a heterologous group of biopolymeric pigments synthesized by diverse prokaryotes and eukaryotes and are widely utilized as bioactive materials and functional polymers in the biotechnology industry. Here, we report the high-level melanin production using a new melanogenic Flavobacterium kingsejongi strain and a recombinant Escherichia coli overexpressing F. kingsejongi 4-hydroxyphenylpyruvate dioxygenase (HPPD).

Results
Melanin synthesis of F. kingsejongi strain was confirmed via melanin synthesis inhibition test, melanin solubility test, genome analysis, and structural analysis of purified melanin from both wild-type F. kingsejongi and recombinant E. coli expressing F. kingsejongi HPPD. The activity of F. kingsejongi HPPD was demonstrated via in vitro assays with 6 × His-tagged and native forms of HPPD. The specific activity of F. kingsejongi HPPD was 1.2 ± 0.03 μmol homogentisate/min/mg-protein. Bioreactor fermentation of F. kingsejongi produced a large amount of melanin with a titer of 6.07 ± 0.32 g/L, a conversion yield of 60% (0.6 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.03 g/L·h, indicating its potential for industrial melanin production. Additionally, bioreactor fermentation of recombinant E. coli expressing F. kingsejongi HPPD produced melanin at a titer of 3.76 ± 0.30 g/L, a conversion yield of 38% (0.38 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.04 g/L·h.

Conclusions
Both strains showed sufficiently high fermentation capability to indicate their potential as platform strains for large-scale bacterial melanin production. Furthermore, F. kingsejongi strain could serve as a model to elucidate the regulation of melanin biosynthesis pathway and its networks with other cellular pathways, and to understand the cellular responses of melanin-producing bacteria to environmental changes, including nutrient starvation and other stresses.
PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway
Authors: Zhang Xitao , Liu Tianlai , Huang Jinlin , He Jianping 
Published: May 2022

Abstract
Background
Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract with high incidence and mortality. In this study, the functions and potential mechanism of phosphatidylinositol-binding clathrin assembly protein (PICALM) in CRC were preliminarily explored.

Methods
Based on the Cancer Genome Atlas database and immunohistochemistry staining, revealing that the expression level of PICALM in CRC tissues was higher than that in adjacent normal tissues.

Results
Moreover, loss-of-function and gain-of-function assays in HCT 116 and RKO cells found that PICALM promotes proliferation and migration of CRC cells and inhibits apoptosis. Consistently, knockdown of PICALM inhibited tumorigenicity of CRC cells in vivo. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that knockdown of PICALM resulted in the enrichment of MAPK signaling pathway. Treatment of CRC cells with MAPK inhibitor reversed the effects of PICALM overexpression on proliferation and apoptosis. In addition, overexpression of PICALM upregulated the protein levels of ERK1/2 (p-ERK1/2), MEK1/2 (p-MEK1/2), p38 (p-p38) and JNK (p-JNK), and these effects were partially alleviated by the treatment of MAPK inhibitor.

Conclusions
In summary, the study presented the new discovery that PICALM promoted CRC progression through ERK/MAPK signaling pathway, which drew further interest regarding its clinical application as a promising therapeutic target.
ncRNAs-mediated high expression of TIMM8A correlates with poor prognosis and act as an oncogene in breast cancer
Authors: Wang Zhonglin , Li Shuqin , Xu Feng , Fu Jingyue , Sun Jie , Gan XinLi , Yang Chuang , Mao Zhongqi 
Published: May 2022

Abstract
Background
Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated.

Methods
Pan-cancer analysis was firstly performed for TIMM8A’s expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model.

Results
We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo.

Conclusion
Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.
ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression
Authors: Liu Junqiang , Chou Zhiyuan , Li Chun , Huang Kai , Wang Xuejian , Li Xiunan , Han Chuanchun , Al-Danakh Abdullah , Li Xiaodong , Song Xishuang 
Published: May 2022

AbstractBackgroundZinc finger and BTB domain-containing 7A (ZBTB7A) is a member of the POK family of transcription factors that plays an oncogenic or tumor-suppressive role in different cancers depending on the type and genetic context of cancer. However, the function and molecular mechanism of ZBTB7A in bladder cancer (BC) remain elusive.MethodsThe role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1.ResultsThe present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC.ConclusionOur data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.
DNA repair and damage pathways in mesothelioma development and therapy
Authors: Malakoti Faezeh , Targhazeh Niloufar , Abadifard Erfan , Zarezadeh Reza , Samemaleki Sahar , Asemi Zatollah , Younesi Simin , Mohammadnejad Reza , Hadi Hossini Seyed , Karimian Ansar , Alemi Forough , Yousefi Bahman 
Published: May 2022

AbstractMalignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.
Exploring theoretical mechanisms of community-engaged research: a multilevel cross-sectional national study of structural and relational practices in community-academic partnerships
Authors: Oetzel John G. , Boursaw Blake , Magarati Maya , Dickson Elizabeth , Sanchez-Youngman Shannon , Morales Leo , Kastelic Sarah , Eder Milton “Mickey” , Wallerstein Nina 
Published: May 2022

Abstract
Background
Community-Based Participatory Research (CBPR) is often used to address health inequities due to structural racism. However, much of the existing literature emphasizes relationships and synergy rather than structural components of CBPR. This study introduces and tests new theoretical mechanisms of the CBPR Conceptual Model to address this limitation.

Methods
Three-stage online cross-sectional survey administered from 2016 to 2018 with 165 community-engaged research projects identified through federal databases or training grants. Participants (N = 453) were principal investigators and project team members (both academic and community partners) who provided project-level details and perceived contexts, processes, and outcomes. Data were analyzed through structural equation modeling and fuzzy-set qualitative comparison analysis.

Results
Commitment to Collective Empowerment was a key mediating variable between context and intervention activities. Synergy and Community Engagement in Research Actions were mediating variables between context/partnership process and outcomes. Collective Empowerment was most strongly aligned with Synergy, while higher levels of Structural Governance and lower levels of Relationships were most consistent with higher Community Engagement in Research Actions.

Conclusions
The CBPR Conceptual Model identifies key theoretical mechanisms for explaining health equity and health outcomes in community-academic partnerships. The scholarly literature’s preoccupation with synergy and relationships overlooks two promising practices—Structural Governance and Collective Empowerment—that interact from contexts through mechanisms to influence outcomes. These results also expand expectations beyond a “one size fits all” for reliably producing positive outcomes.
Two-dimensional metal-organic frameworks: from synthesis to bioapplications
Authors: Wang Weiqi , Yu Yuting , Jin Yilan , Liu Xiao , Shang Min , Zheng Xiaohua , Liu Tingting , Xie Zhigang 
Published: May 2022

AbstractAs a typical class of crystalline porous materials, metal–organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.
Graphical Abstract