KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Our studies have revealed that KIF2C plays a crucial role in tumor proliferation and metastasis in HNSCC. The results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels and is closely associated with lymph node metastasis. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicate that the differentially expressed genes are enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Moreover, the established protein-protein interaction network identifies KIF2C as a potential hub gene in HNSCC. Knockdown of KIF2C has been demonstrated to significantly reduce cell migration and invasion ability, leading to cell cycle arrest, a high proportion of abnormal cell apoptosis, and cell chromosome division mismatches in the HNSCC cell line. Downstream genes such as PDGFA, EGFR, TP63, SNAI2, KRT5, and KRT14 were found to be down-regulated, and multiple critical pathways, including mTOR, ERK, and PI3K-AKT pathways, were inactivated as a result of KIF2C knockdown. These findings provide strong evidence for the crucial role of KIF2C in HNSCC and suggest that targeting KIF2C may be a promising therapeutic strategy for this disease. Knockdown of KIF2C has been shown to significantly inhibit tumor proliferation in nude mice, demonstrating the potential therapeutic role of KIF2C in HNSCC treatment.

Association analysis of polymorphisms in SLK, ARHGEF9, WWC2, GAB3, and FSHR genes with reproductive traits in different sheep breeds.

The aim was to investigate the relationship between polymorphisms of gene mutation loci and reproductive traits in local sheep breeds (Duolang Sheep) and introduced sheep breeds (Suffolk, Hu Sheep) in Xinjiang to provide new molecular markers for the selection and breeding of high fecundity sheep. The expression pattern of typing successful genes in sheep tissues was investigated by RT-qPCR technology, providing primary data for subsequent verification of gene function. The 26 mutation loci of WWC2, ARHGEF9, SLK, GAB3, and FSHR genes were typed using KASP. Association analyses were performed using SPSS 25.0, and the typing results showed that five genes with six loci, WWC2 (g.14962207 C>T), ARHGEF9 (g.48271079 C>A), SLK (g.27107842 T>C, g.27108855 G>A), GAB3 (g.86134602 G>A), and FSHR (g.80789180 T>G) were successfully typed. The results of the association analyses showed that WWC2 (g.14962207 C>T), SLK (g.27108855 G>A), ARHGEF9 (g.48271079 C>A), and FSHR (g.80789180 T>G) caused significant or extremely significant effects on the litter size in Duolang, Suffolk and Hu Sheep populations. The expression distribution pattern of the five genes in 12 sheep reproduction-related tissues was examined by RT-qPCR. The results showed that the expression of the SLK gene in the uterus, the FSHR gene in the ovary, and the ARHGEF9 gene in hypothalamic-pituitary-gonadal axis-related tissues were significantly higher than in the tissues of other parts of the sheep. WWC2 and GAB3 genes were highly expressed both in reproductive organs and visceral tissues. In summary, the WWC2 (g.14962207 C>T), SLK (g.27108855 G>A), ARHGEF9 (g.48271079 C>A), and FSHR (g.80789180 T>G) loci can be used as potential molecular markers for detecting differences in reproductive performance in sheep. Due to variations in typing results, the SLK (g.27107842 T>C) and GAB3 (g.86134602 G>A) loci need further validation.

Validation and Analysis of COIL, a Gene Associated with Multiple Lambing Traits in Sheep.

In a past study, the team used specific-locus amplified fragment sequencing (SLAF sequencing) to detect single-nucleotide polymorphisms (SNPs) contributing to the differences in lambing numbers in Xinjiang sheep. This study verified the correlation between the COIL gene and lambing number characters in sheep and explored its possible mechanism of action. In this study, three SNPs in the COIL gene, namely COILSNP1 (rs7321466), COILSNP2 (rs7314134), and COILSNP3 (rs7321563), were explored in terms of their possible mechanism of action. A tissue expression profiling analysis revealed that the COIL gene was significantly more expressed in the uterus and ovaries than in other tissues (p < 0.05), whereas an association analysis revealed that the number of lambs born was significantly different among individuals with different genotypes of this COILSNP1 (p < 0.05). The Cell Counting Kit-8(CCK-8) revealed that the overexpression of the COIL gene significantly increased the proliferation of mouse ovarian fibroblasts and sheep fibroblasts (p < 0.05). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) revealed that the overexpression of the COIL gene significantly increased the activity of sheep fibroblasts (p < 0.01) and mouse ovarian fibroblasts (p < 0.05). The overexpression of the COIL gene affected the biogenesis pathway of spliceosomal U snRNPs by validating protein network connections. This activity affects ovulation, embryonic development, and changes in lambing size in sheep.

Pediatric granular cell tumor of the larynx: A case report and literature review.

An 8-year-old child was admitted to our ENT department for a year because of a hoarse voice. An endoscopic examination displayed that a cystic, solid lesion can be seen in the right subglottis. The lesion was removed using a CO2 laser under general anesthesia. Postoperative histopathology confirmed granular cell tumor (GCT), S-100(+), vimentin (+), and SOX-10(+). GCT, also known as the Abrikossoff tumor, is a rare benign tumor that rarely occurs in the larynx, particularly in children. This case report emphasizes that considerable attention should be given to the differential diagnosis of the laryngeal granulosa cell tumor. Given the recurrence risk of GCT, long-term postoperative follow-up is necessary.

Integrating genome-wide methylation and transcriptome-wide analyses to reveal the genetic mechanism of milk traits in Kazakh horses.

Horse Milk has important quantitative characteristics and high economic value. However, the DNA methylation regulators involved in horse milk traits have not been clarified. To explore the important role of genome-wide DNA methylation in regulating equine milk yield, this study systematically investigated the genome-wide DNA methylation profiles of Kazakh horse blood by comparing a high-production group (HP, average daily milk yield of 7.5 kg) and low-production group (LP, average daily milk yield of 3.2 kg) using deep whole-genome bisulfite sequencing. First, both groups showed similar proportions of methylation at CpG sites. Subsequently, we identified 26,677 differential methylated regions (DMRs) of CG, 15 DMRs of CHG, 480 DMRs of CHH and 8268 DMR-related genes (DMGs). GO and KEGG analyses revealed that some DMGs were involved in regulating milk and milk component formation. By combining the WGBS-seq and the previous RNA-seq data, a total of 94 overlapping genes were obtained. Finally, we found that 9 DMGs are likely involved in milk production by Kazakh horses.

A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer.

BACKGROUND: Cuproptosis is a novel form of cell death that is highly related to mitochondrial metabolism and mediated by protein lipoacetylation. This study systematically assessed the differential expression and genetic alterations of cuproptosis-related genes (CRGs) in head and neck squamous-cell carcinoma (HNSCC) and constructed CRG risk models to predict survival in patients with HNSCC. METHODS: We investigated the expression of 19 CRGs in HNSCC and noncancerous tissues, and the relationship between mutation load, immune infiltration, and clinical features was examined based on data from public databases. CRG risk models were constructed by univariate Cox analysis and lasso regression and validated by independent datasets for their accuracy in predicting survival outcomes in patients with HNSCC. The expression distribution of CRGs in HNSCC cells was further explored in the HNSCC single-cell sequencing dataset. RESULTS: NFE2L2, ATP7A, FDX1, LIAS, DLD, DLAT, PDHB, MTF1 and DBT were highly expressed in noncancerous samples, while GLS, CDKN2A and DLST were highly expressed in HNSCC samples (p < 0.05). Gene copy number variation frequency (CNV) revealed CDKN2A, FDX1 and DLAT copy number deletions and LIPT2 and NFE2L2 copy number increases. Ten CRGs were used to construct a risk model to predict overall survival (OS) in HNSCC, yielding reduced OS in the high-risk group compared to the low-risk group, training group (p = 9.733e - 05), and testing group (p = 0.040). The CRG risk model was significantly correlated with various immune cells, regulatory T cells (Tregs) and memory B cells were significantly negatively correlated (p = 0.027, p = 0.00084), and resting CD4 memory T cells was significantly positively correlated (p = 9e - 04). Most CRGs significantly affected the clinical characteristics of HNSCC. NFE2L2, SLC31A1, PDHA1, CDKN2A and DBT were highly expressed in epithelial cells of HNSCC, while SLC31A1, DBT and NFE2L2 were highly expressed in T cells, and SLC31A1 in B cells. In monocytes, NFE2L2, SLC31A1 and PDHA1 were highly expressed. CONCLUSION: The CRG risk model can be used as a potential prognostic factor for HNSCC patients and may provide new insights into cancer treatment from the perspective of copper metabolism.

Candidate genes for litter size in Xinjiang sheep identified by Specific Locus Amplified Fragment (SLAF) sequencing.

The aim of this study was to investigate the selection signatures at a genome-wide level in 'Pishan' sheep using Specific Locus Amplified Fragment (SLAF)-seq. Blood samples from 126 ewes were sequenced using SLAF tags, and the ovarian tissues from 8 ewes (Bashbay sheep, a single litter size group (SG group); 'Pishan' sheep, double litter size group (DG group)) were collected to detect expression levels by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Selection signature analysis was performed using global fixation index (Fst) and nucleotide diversity (π) ratio. A total of 1,192,168 high-quality SLAFs were identified. Notably, 2380 candidate regions under selection using two approaches were identified. A total of 2069 genes were identified, which were involved in dopaminergic synapses, thyroid hormone synthesis, ovarian steroidogenesis and thyroid hormone signalling pathways. Furthermore, Growth Differentiation Factor 9 (GDF9), Period Circadian Regulator 2 (PER2), Thyroid Stimulating Hormone Receptor (TSHR), and Nuclear Receptor Coactivator 1 (NCOA1) reside within these regions and pathways. The expression levels of GDF9 and PER2 genes in sheep tissue of the DG group were significantly higher than those in the SG group. These genes are interesting candidates for litter size and provide a starting point for further identification of conservation strategies for 'Pishan' sheep.

Susceptibility Analysis of Geohazards in the Longmen Mountain Region after the Wenchuan Earthquake.

Multitemporal geohazard susceptibility analysis can not only provide reliable results but can also help identify the differences in the mechanisms of different elements under different temporal and spatial backgrounds, so as to better accurately prevent and control geohazards. Here, we studied the 12 counties (cities) that were severely affected by the Wenchuan earthquake of 12 May 2008. Our study was divided into four time periods: 2008, 2009-2012, 2013, and 2014-2017. Common geohazards in the study area, such as landslides, collapses and debris flows, were taken into account. We constructed a geohazard susceptibility index evaluation system that included topography, geology, land cover, meteorology, hydrology, and human activities. Then we used a random forest model to study the changes in geohazard susceptibility during the Wenchuan earthquake, the following ten years, and its driving mechanisms. We had four main findings. (1) The susceptibility of geohazards from 2008 to 2017 gradually increased and their spatial distribution was significantly correlated with the main faults and rivers. (2) The Yingxiu-Beichuan Fault, the western section of the Jiangyou-Dujiangyan Fault, and the Minjiang and Fujiang rivers were highly susceptible to geohazards, and changes in geohazard susceptibility mainly occurred along the Pingwu-Qingchuan Fault, the eastern section of the Jiangyou-Dujiangyan Fault, and the riparian areas of the Mianyuan River, Zagunao River, Tongkou River, Baicao River, and other secondary rivers. (3) The relative contribution of topographic factors to geohazards in the four different periods was stable, geological factors slowly decreased, and meteorological and hydrological factors increased. In addition, the impact of land cover in 2008 was more significant than during other periods, and the impact of human activities had an upward trend from 2008 to 2017. (4) Elevation and slope had significant topographical effects, coupled with the geological environmental effects of engineering rock groups and faults, and river-derived effects, which resulted in a spatial aggregation of geohazard susceptibility. We attributed the dynamic changes in the areas that were highly susceptible to geohazards around the faults and rivers to the changes in the intensity of earthquakes and precipitation in different periods.

Relationship Between Social Capital and Depressive Symptoms Among Type 2 Diabetes Mellitus Patients in Northwest China: A Mediating Role of Sleep Quality.

Objective: There are few studies about the relationship between social capital (SC) and depression among type 2 diabetes mellitus (T2DM) patients, and the mechanism explaining how SC leads to decreased depression is unclear. The current study aims to explore the relationship between SC and depressive symptoms among the T2DM patients in northwest China, with a particular focus on the mediating role of sleep quality. Methods: A cross-sectional study of 1,761 T2DM patients from Ningxia Province was conducted. The Center for Epidemiological Survey Depression Scale (CES-D) and self-report sleep quality questionnaire coupled with the SC scales were administered during the face-to-face survey. The Bootstrap methods PROCESS program is employed to test the mediation model. Results: The prevalence of depressive symptoms among T2DM patients was 24.8%. After controlling for covariates, the SC (r = -0.23, p < 0.001) was negatively correlated with CES-D score; the sleep quality was also negatively correlated with CES-D score (r = -0.31, p < 0.001); and the SC was positively correlated with sleep quality (r = 0.10, p < 0.001). Logistic regression analysis showed that SC was inversely related to the risk of depressive symptoms. Meanwhile, sleep quality was negatively associated with depressive symptoms. Sleep quality has mediated the relationship between SC and depressive symptoms among T2DM patients (explaining 12.6% of the total variance). Conclusions: We elucidated how SC interacted with depressive symptoms through the mediation pathway of sleep quality using a representative sample of the Chinese diabetes patients. The findings indicate that the improvement of SC and sleep quality may help in maintaining mental health among T2DM patients. Hence, clinicians can suggest that patients communicate more with others to improve the SC and, in turn, maintain their health.

Identification of novel genes associated with litter size of indigenous sheep population in Xinjiang, China using specific-locus amplified fragment sequencing technology.

BACKGROUND: There are abundant sheep breed resources in the Xinjiang region of China attributing to its diverse ecological system, which include several high-litter size sheep populations. Previous studies have confirmed that the major high prolificacy gene cannot be used to detect high litter size. Our research team found a resource group in Pishan County, southern Xinjiang. It showed high fertility with an average litter size of two to four in one birth, excellent breast development, and a high survival rate of lambs. In the present study, we used this resource as an ideal sample for studying the genetic mechanisms of high prolificacy in sheep. METHODS: Indigenous sheep populations from Xinjiang, with different litter sizes, were selected for the research, and specific-locus amplified fragment sequencing (SLAF-seq) technology was used to comprehensively screen single nucleotide polymorphisms (SNPs) from the whole genome that may cause differences in litter size. Novel genes associated with litter size of sheep were detected using genome-wide association studies (GWAS), providing new clues revealing the regulation mechanism of sheep fecundity. Candidate genes related to ovulation and litter size were selected for verification using Kompetitive Allele Specific polymerase chain reaction (KASP) cluster analysis. RESULTS: We identified 685,300 SNPs using the SLAF-seq technique for subsequent genome-wide analysis. Subsequently, 155 SNPs were detected at the genome-wide level. Fourteen genes related to sheep reproduction were notated: COIL, SLK, FSHR, Plxna3, Ddx24, CXCL12, Pla2g7, ATP5F1A, KERA, GUCY1A1, LOC101107541, LOC101107119, LOC101107809, and BRAF. Based on literature reports, 30 loci of seven genes and candidate genes (CXCL12, FSHR, SLK, GUCY1A1, COIL, LOC101107541, and LOC101107119) related to ovulation and litter size were selected for verification using KASP cluster analysis. Among them, nine loci of three genes were successfully genotyped. Three loci of FSHR (GenBank ID: 443299, g. 75320741G>A site), GUCY1A1 (GenBank ID: 101110000, g. 43266624C>T site), and COIL (GenBank ID: 101123134, g. 7321466C>G site) were found to be significantly or extremely significantly associated with litter size. These three loci are expected to be used as molecular markers to determine differences in litter size in sheep.