bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of hub genes and regulatory networks in histologically unstable carotid atherosclerotic plaque by bioinformatics analysis
Authors: Guo Julong , Ning Yachan , Su Zhixiang , Guo Lianrui , Gu Yongquan 
Published: June 2022

AbstractObjectiveThis study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets.MethodsThree transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein–protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks.ResultsA total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors.ConclusionsWe screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets.
CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA
Authors: Yao Bing , Zhang Qinglin , Yang Zhou , An Fangmei , Nie He , Wang Hui , Yang Cheng , Sun Jing , Chen Ke , Zhou Jingwan , Bai Bing , Gu Shouyong , Zhao Wei , Zhan Qiang 
Published: June 2022

Abstract
Background
Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive.

Methods
High-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms.

Results
Here, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression.

Conclusions
Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC.
An update of Nrf2 activators and inhibitors in cancer prevention/promotion
Authors: Pouremamali Farhad , Pouremamali Amir , Dadashpour Mehdi , Soozangar Narges , Jeddi Farhad 
Published: June 2022

AbstractNF-E2-related factor 2 (Nrf2) protein is a basic-region leucine zipper transcription factor that defends against endogenous or exogenous stressors. By inducing several cytoprotective and detoxifying gene expressions, Nrf2 can increase the sensitivity of the cells to oxidants and electrophiles. Transient Nrf2 activation, by its specific activators, has protective roles against carcinogenesis and cancer development. However, permanent activation of Nrf2 promotes various cancer properties, comprising malignant progression, chemo/radio resistance, and poor patient prognosis. Taken together, these findings suggest that reaching an optimal balance between paradoxical functions of Nrf2 in malignancy may render a selective improvement to identify therapeutic strategies in cancer treatment. In this review, we describe lately discovered Nrf2 inducers and inhibitors, and their chemopreventive and/or anticancer activities.
Aberrant SPOP-CHAF1A ubiquitination axis triggers tumor autophagy that endows a therapeutical vulnerability in diffuse large B cell lymphoma
Authors: Yan Wei , Shi Xue , Wang Huihan , Liao Aijun , Yang Wei 
Published: June 2022

Abstract
Purpose
Aberrant epigenetic changes, like DNA methylation, histone modifications, or ubiquitination, could trigger metabolic disorders in human cancer cells. This study planed to uncover the biological roles of epigenetic SPOP/CHAF1A axis in modulating tumor autophagy during Diffuse large B-cell lymphoma (DLBCL) tumorigenesis.

Materials and methods
The Immunohistochemistry (IHC) was performed to assess the CHAF1A expressions. The expression data of CHAF1A was derived from The Cancer Genome Atlas (TCGA), GSE32918 and GSE83632 datasets. Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan–Meier survival curve analysis. The colony generation assay, Transwell assay and CCK-8 assays were conducted for the in vitro assays. The in vivo ubiquitination assays were used to assess regulations of SPOP on CHAF1A. The Chromatin immunoprecipitation (ChIP) assays were used to uncover epigenetic regulations of CHAF1A on TFEB. The relevant DLBCL cells were subcutaneously injected to SCID beige mice to establish the xenograft models.

Results
Bioinformatic results revealed that CHAF1A expressed highly in DLBCL that were validated in patients samples. Patients with high CHAF1A suffered from inferior prognosis with shorter survival months relative to those with low CHAF1A. High CHAF1A enhanced DLBCL aggressiveness, including cell proliferation, migration and in vivo growth. Mechanistically, E3 ubiquitin ligase SPOP binds to and induces the degradative ubiquitination of CHAF1A via recognizing a consensus SPOP-binding motif in CHAF1A. SPOP is down-regulated in DLBCL and habours two DLBCL-associated mutations. Deficient SPOP leads to accumulated CHAF1A proteins that promote malignant features of DLBCL. Subsequently, ChIP-qPCR assay revealed that CHAF1A directly binds to TFEB promoters to activate the expressions. High CHAF1A could enhance the transcriptional activity of TFEB and downstream genes. The SPOP/CHAF1A axis modulates TFEB-dependent transactivation to regulate the lysosomal biogenesis and autophagy. The in vivo models suggested that TFEB inhibition is effective to suppress growth of SPOP-deficient DLBCLs.

Conclusions
CHAF1A is aberrantly elevated in SPOP-deficient DLBCL. The in‐depth mechanism understanding of SPOP/CHAF1A/TFEB axis endows novel targets for DLBCL treatment.
White matter pathology in alzheimer’s transgenic mice with chronic exposure to low-level ambient fine particulate matter
Authors: Chen Ta-Fu , Lee Sheng-Han , Zheng Wan-Ru , Hsu Ching-Chou , Cho Kuan-Hung , Kuo Li-Wei , Chou Charles C.-K. , Chiu Ming-Jang , Tee Boon Lead , Cheng Tsun-Jen 
Published: June 2022

Abstract
Background
Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer’s disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution.

Results
6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 μg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract.

Conclusions
In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.
The Social Competence Promotion Program among Young Adolescents (SCPP-YA) in Chile (“Mi Mejor Plan”) for substance use prevention among early adolescents: study protocol for a randomized controlled trial
Authors: Gaete Jorge , Inzunza Constanza , Ramírez Saray , Valenzuela Daniela , Rojas Cristian , Araya Ricardo 
Published: June 2022

Abstract
Background
Substance use is highly prevalent among children and adolescents in Chile, and it is known how it impacts their health and social adjustment. The call for effective prevention of substance use among children adolescents has resulted in numerous school-based programs, and particularly, the Social Competence Promotion Program among Young Adolescents (SCPP-YA) has been proved to be successful for promoting social and problem-solving skills in addition to preventing substance abuse in the US population. The purpose of this study is to test the effectiveness of the Social Competence Promotion Program among Young Adolescents (SCPP-YA) in Chile (“Mi Mejor Plan”).

Methods
This is a cluster randomized controlled trial, parallel-group type, where “Mi Mejor Plan” is compared to standard school preventive curricula in control schools. A total of 10 schools and 600 adolescents are expected to be recruited and randomized with 1:1 allocation. During formative work, the SCPP-YA program was culturally adapted to Chile. The effectiveness of this program will be assessed using the European Drug Addiction Prevention Trial Questionnaire (EU-Dap), measuring substance use prevalence and risk and protective factors in baseline, post-intervention, and 4 months after the end of the intervention.

Discussion
The proposed study will be the first to test the effectiveness of the Social Competence Promotion Program among Young Adolescents (SCPP-YA) in Chile in a cluster randomized control trial and also the first study evaluating this program in Spanish-speaking Latin America. SCPP-YA has been implemented successfully in the USA. Thus, if the effects of the program are positive, wide implementation in Chile and Latin American countries is possible soon.

Trial registration
Clinical Trials NCT04236947. Registered on January 22, 2020.
pH regulatory divergent point for the selective bio-oxidation of primary diols during resting cell catalysis
Authors: Hua Xia , Zhang ChenHui , Han Jian , Xu Yong 
Published: June 2022

Abstract
Background
Hydroxyl acid is an important platform chemical that covers many industrial applications due to its dual functional modules. At present, the traditional technology for hydroxyl acid production mainly adopts the petroleum route with benzene, cyclohexane, butadiene and other non-renewable resources as raw materials which violates the development law of green chemistry. Conversely, it is well-known that biotechnology and bioengineering techniques possess several advantages over chemical methods, such as moderate reaction conditions, high chemical selectivity, and environmental-friendly. However, compared with chemical engineering, there are still some major obstacles in the industrial application of biotechnology. The critical issue of the competitiveness between bioengineering and chemical engineering is products titer and volume productivity. Therefore, based on the importance of hydroxyl acids in many fields, exploring a clean, practical and environmental-friendly preparation process of the hydroxyl acids is the core purpose of this study.

Results
To obtain high-purity hydroxyl acid, a microbiological regulation for its bioproduction by Gluconobacter oxydans was constructed. In the study, we found a critical point of chain length determine the end-products. Gluconobacter oxydans catalyzed diols with chain length ≤ 4, forming hydroxyl acids, and converting 1,5-pentylene glycol and 1,6-hexylene glycol to diacids. Based on this principle, we successfully synthesized 75.3 g/L glycolic acid, 83.2 g/L 3-hydroxypropionic acid, and 94.3 g/L 4-hydroxybutyric acid within 48 h. Furthermore, we directionally controlled the products of C5/C6 diols by adjusting pH, resulting in 102.3 g/L 5‑hydroxyvaleric acid and 48.8 g/L 6-hydroxycaproic acid instead of diacids. Combining pH regulation and cell-recycling technology in sealed-oxygen supply bioreactor, we prepared 271.4 g 5‑hydroxyvaleric acid and 129.4 g 6-hydroxycaproic acid in 6 rounds.

Conclusions
In this study, a green scheme of employing G. oxydans as biocatalyst for superior-quality hydroxyl acids (C2–C6) production is raised up. The proposed strategy commendably demonstrated a novel technology with simple pH regulation for high-value production of hydroxyl acids via green bioprocess developments.
3DFAACTS-SNP: using regulatory T cell-specific epigenomics data to uncover candidate mechanisms of type 1 diabetes (T1D) risk
Authors: Liu Ning , Sadlon Timothy , Wong Ying Y. , Pederson Stephen , Breen James , Barry Simon C. 
Published: June 2022

Abstract
Background
Genome-wide association studies (GWAS) have enabled the discovery of single nucleotide polymorphisms (SNPs) that are significantly associated with many autoimmune diseases including type 1 diabetes (T1D). However, many of the identified variants lie in non-coding regions, limiting the identification of mechanisms that contribute to autoimmune disease progression. To address this problem, we developed a variant filtering workflow called 3DFAACTS-SNP to link genetic variants to target genes in a cell-specific manner. Here, we use 3DFAACTS-SNP to identify candidate SNPs and target genes associated with the loss of immune tolerance in regulatory T cells (Treg) in T1D.

Results
Using 3DFAACTS-SNP, we identified from a list of 1228 previously fine-mapped variants, 36 SNPs with plausible Treg-specific mechanisms of action. The integration of cell type-specific chromosome conformation capture data in 3DFAACTS-SNP identified 266 regulatory regions and 47 candidate target genes that interact with these variant-containing regions in Treg cells. We further demonstrated the utility of the workflow by applying it to three other SNP autoimmune datasets, identifying 16 Treg-centric candidate variants and 60 interacting genes. Finally, we demonstrate the broad utility of 3DFAACTS-SNP for functional annotation of all known common (> 10% allele frequency) variants from the Genome Aggregation Database (gnomAD). We identified 9376 candidate variants and 4968 candidate target genes, generating a list of potential sites for future T1D or other autoimmune disease research.

Conclusions
We demonstrate that it is possible to further prioritise variants that contribute to T1D based on regulatory function, and illustrate the power of using cell type-specific multi-omics datasets to determine disease mechanisms. Our workflow can be customised to any cell type for which the individual datasets for functional annotation have been generated, giving broad applicability and utility.
SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder
Authors: Dong Tao , Zhao Yan , Jin Hai-Feng , Shen Lei , Lin Yan , Si Long-Long , Chen Li , Liu Ji-Cheng 
Published: June 2022

AbstractBackgroundα-1-syntrophin (SNTA1), a protein encoded bySNTA1, is highly expressed in human cardiomyocytes. Mutations inSNTA1are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype ofSNTA1-deficiency using human cardiomyocytes.MethodsSNTA1was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated withSNTA1-deficient cardiomyocytes were investigated.ResultsSNTA1was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system.SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment ofSNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility.ConclusionSNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. TheSNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.
Morphological characteristics of the surgical neck region in the proximal humerus at different ages
Authors: Guo Jialiang , Zhou Yali , Shang Meishuang , Chen Wei , Hou Zhiyong , Zhang Yingze , Dong Weichong 
Published: June 2022

AbstractBackgroundThe objective of the study was to demonstrate the cortical thickness character in the humeral surgical neck region using 3D cortical bone mapping technique and try to illustrate its morphological changes with age.Material and methodsNormal individuals, including 11 volunteers younger than 18 years, 87 adult men and 46 adult women, were enrolled. The cortical thickness and height of the surgical neck region was measured with Mimic and 3 Matic software. The height of the region was compared and measured. People with an age of 18–30 years was identified as Group I, people in 31–40 years as Group II, people in 41–50 years as Group III, people in 51–60 years as Group IV, and Group V including people ≥ 61 years.ResultsCompared with the baseline Group I, cortical thickness was significantly decreased by 0.52 mm (P = 0.006) in Group III, by 0.76 mm (P < 0.001) in Group IV, and by 0.77 mm (P < 0.001) in Group V. Age moderately predicted cortical thickness withr = −0.5481. The height of the cortical change region was significantly decreased by 2.25 mm (P = 0.007) in Group II, by 2.98 mm (P < 0.001) in Group III, and by 2.07 mm (P = 0.02) in Group IV. However, no significant decrease was illustrated in Group V (0.57 mm) (P = 0.891). The relation between age and the height of the cortical thickness change region was nonlinear.ConclusionsThis study identified an obvious decrease in cortical thickness with aging, and the height was curve fitted with aging in surgical neck region.
A confirmation of vertical acoustic resonance and field-aligned current generation just after the 2022 Hunga Tonga Hunga Ha’apai volcanic eruption
Authors: Iyemori Toshihiko , Nishioka Michi , Otsuka Yuichi , Shinbori Atsuki 
Published: June 2022

AbstractA strong volcanic eruption caused a clear vertical acoustic resonance between the sea surface and the thermosphere. Its effects are observed as geomagnetic and GPS-TEC oscillations near the volcano and its geomagnetic conjugate area. The geomagnetic oscillations are observed at Apia and Honolulu geomagnetic observatories with amplitude of about 2 nT and 0.2 nT, respectively. The volcanic eruption started around 04:14 UT on January 15, 2022. The oscillations appeared at 04:21UT at Apia, Samoa, only about 7 min after the start of eruption. Because the distance between the volcano and Apia is about 841 km, it takes about 40 min for a sound wave to propagate from the volcano to Apia. Therefore, it is more plausible to assume that the magnetic oscillation observed at Apia about 7 min after the eruption is caused by the sound waves propagated vertically upward to the ionosphere and generated an electric current. The coherent appearance of geomagnetic oscillation at Honolulu located near the geomagnetic conjugate point of the volcano strongly support the idea that the ionospheric current generated over the volcano diverted as a field-aligned current which flew to the opposite hemisphere and caused the geomagnetic oscillation at Honolulu. The earliest start of GPS-TEC oscillation was around 04:15UT near the volcanic eruption, and it was around 04:20 UT at KOKV station in Hawaii. The time-lag of the TEC variations between Samoa and Hawaii obtained by a cross-correlation analysis is 4.5 min or 8.5 min. These time differences are much smaller than the travel time of the seismic waves from the volcano to Hawaii islands. Therefore, it is suggested that the electric field transmitted along geomagnetic field caused the TEC variation observed over Hawaii Islands. A sawtooth waveform of geomagnetic oscillation observed at Apia and Honolulu is analyzed and a possible generation mechanism is discussed.
Graphical Abstract