Single-cell transcriptome analysis reveals characteristic transcription factors in polydactyly.

OBJECTIVE: The study aims to provide guidance on the identification of multiple-digit malformations as potential biomarkers and therapeutic targets. MATERIALS AND METHODS: Single-cell RNA sequencing (scRNA-seq) data of four multiple-finger malformation samples were downloaded from the GEO public database. Fibroblasts and keratinocytes were divided into cellular subpopulations and the transcription factors of different subpopulations were analyzed. The regulatory network of transcription factors and their target genes were constructed to analyze the functionality of regulons. RESULTS: Examination of the transcriptional profile data from 11,806 single cells uncovered significant associations between regulons and cell function in polydactyly. Specifically, the analysis highlighted the involvement of HOX family members and GLI2 transcription factors, including HOXD13, MSX2, LHX2, EMX2, LEF1, CREB3L2, and LHX2, in the polydactyly process within fibroblast cells. Furthermore, it sheds light on the roles of HES2 and GLIS1 in the formation and development of keratinocytes. CONCLUSIONS: Significant presence of transcription factors, especially HOXD13, MSX2, and LHX2, may be strongly related to the development of polydactyly.

Tooth Discoloration from 2 Silver Fluorides Used in Adults with Special Needs: A Randomized Trial.

BACKGROUND: Discoloration of carious lesions after application of silver diamine fluoride lowers patient acceptance and limits its wider use for caries arrest. OBJECTIVE: To assess lesion and tooth color changes from 2 novel silver fluoride (AgF) products and its relationship to caries activity (clinical visuo-tactile scores) and bacterial load (using laser fluorescence with the DIAGNOdent). METHODS: A split-mouth design was followed, with matched smooth surface carious lesions in the same arch in adults with special needs randomized for 1-min treatments with AgF/potassium iodide (KI) (Riva Star Aqua, SDI) and AgF/stannous fluoride (SnF2) (Caries Status Disclosing Solution; Whiteley). Standardized images taken at baseline, immediately postoperatively, and at 3-mo review were subjected to digital image analysis to calculate delta-E and to track changes in luminosity of carious lesions. RESULTS: Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Significantly greater changes were seen in treated lesions than in the adjacent noncarious natural tooth structure, both immediately after treatment and at the 3-mo review (P < 0.0001). Color change and caries activity were not affected by tooth type, tooth location, plaque status, salivary status, or special needs condition. AgF/SnF2 caused transitory darkening immediately on application, while AgF/KI caused the immediate formation of yellow deposits (silver iodide). Both products caused significant darkening of treated lesions at 3 mo (P = 0.0009; P = 0.0361), with no differences between them (P = 0.506). Responding lesions showed larger and more perceptible color changes immediately after either AgF application (P = 0.002; P = 0.024). CONCLUSIONS: Both AgF products were highly effective for caries arrest in this patient population. Despite minor differences in the appearance of treated lesions at the time of application, both products lead to similar darkening of treated sites at 3 mo. KNOWLEDGE TRANSFER STATEMENT: This study shows the usefulness of silver fluoride used in conjunction with potassium iodide or stannous fluoride for achieving caries arrest in smooth surface lesions in adults with special needs. Patients need to be informed that long-term staining of the lesion occurs with both, similar to silver diamine fluoride.

A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.

Intellectual disability (ID) is associated with an increased risk of developing psychiatric disorders, suggesting a common underlying genetic factor. Importantly, altered signaling and/or expression of regulator of G protein signaling 6 (RGS6) is associated with ID and numerous psychiatric disorders. RGS6 is highly conserved and undergoes complex alternative mRNA splicing producing ~36 protein isoforms with high sequence similarity historically necessitating a global approach in functional studies. However, our recent analysis in mice revealed RGS6 is most highly expressed in CNS with RGS6L(+GGL) isoforms predominating. A previously reported genetic variant in intron 17 of RGS6 (c.1369-1G>C), associated with ID, may provide further clues into RGS6L(+GGL) isoform functional delineation. This variant was predicted to alter a highly conserved canonical 3' acceptor site creating an alternative branch point within exon 18 (included in a subset of RGS6L(+GGL) transcripts) and a frameshift forming an early stop codon. We previously identified this alternative splice site and demonstrated its use generates RGS6Lζ(+GGL) isoforms. Here, we show that the c.1369-1G>C variant disrupts the canonical, preferred (>90%) intron 17 splice site and leads to the exclusive use of the alternate exon 18 splice site, inducing disproportionate expression of a subset of isoforms, particularly RGS6Lζ(+GGL). Furthermore, RGS6 global knockout mice do not exhibit ID. Thus, ID caused by the c.1369-1G>C variant likely results from altered RGS6 isoform expression, rather than RGS6 isoform loss. In summary, these studies highlight the importance of proper RGS6 splicing and identify a previously unrecognized role of G protein signaling in ID.

[Efficacy comparison between a new generation of artificial ligaments and bone-patellar tendon-bone autograft for anterior cruciate ligament revision].

Objective: To compare the clinical efficacy of a new generation of ligaments (LARS artificial ligament) and bone-patellar tendon-bone (BPTB) autograft as grafts in anterior cruciate ligament (ACL) revision. Methods: A retrospective cohort study. The clinical data of 54 patients who underwent ACL revision from January 2018 to June 2020 in the First Hospital Affiliated to Army Medical University were retrospectively analyzed. There were 44 males and 10 females with a mean age of (28.5±7.7) years (15-45 years). Among them, 24 cases underwent ACL revision with LARS artificial ligament (LARS group), the other 30 cases underwent ACL revision with BPTB (BPTB group). The subjective and objective knee joint evaluation indexes were compared between the two groups to evaluate the clinical efficacy. The subjective evaluation indexes included Tegner score, Lysholm score and the International Knee Documentation Committee (IKDC) score. The objective evaluation indexes included the Lachman test, pivot-shift test, the anterior tibial translation (ATT) measurement at the weight-bearing position and the rate of patients returned to pre-injury sports. Results: The follow-up period was (32.8±5.3) months (24-42 months). At the last follow-up, the IKDC score, Tegner score and Lysholm score in the two groups significantly increased when compared with those before surgery (all P<0.05), and there was no significant difference in those indexes between the two groups (all P>0.05). The ATT measurement in the weight-bearing position was (3.1±0.7) mm in the LARS group and it was (4.1±0.9) mm in the BPTB group, which were significantly improved when compared with those before surgery (both P<0.05), and it was better in the LARS group than in the BPTB group (P<0.05). Postoperative Lachman test and pivot-shift test results in the LARS group were better than those in the BPTB group with statistically significant difference (both P<0.05). The rate of patients returned to pre-injury sports one year after surgery was 79.2%(19/24) in the LARS group and it was 50.0%(15/30) in the BPTB group, and the difference was statistically significant (P=0.029). Conclusions: Both LARS artificial ligament and BPTB autograft can achieve good short-term clinical efficacy in ACL revision, but LARS artificial ligament group has more advantages than BPTB autograft group in knee stability and early return to sports.

[The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice].

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

[MiR-4772 modulates tumor immune microenvironment by regulating immune- related genes in ovarian cancer].

OBJECTIVE: To explore the regulatory role of miR-4772 in the formation of tumor immune microenvironment in ovarian cancer. METHODS: The optimal cutoff level of PD-L1 expression was calculated based on data from 294 ovarian cancer patients in the TCGA database. The differentially expressed genes (DEGs) between high and low PD-L1 expression groups were screened, and the important DEGs were identified by correlation analysis. WGCNA analysis was performed to select the weighted genes and PD-L1-related miRNAs, from which the hub genes were obtained by intersection analysis. ssGSEA analysis was used to evaluate the effect of PD-L1 and miR-4772 expressions on the tumor immune microenvironment in ovarian cancer. KEGG analysis was used to identify the involved signal pathways, and the interactions between the hub genes were mapped by protein-protein interaction (PPI) analysis. Survival analysis was carried out to identify the survival-related hub genes, and the results were validated using the data of 399 patients with ovarian cancer from GEO database and the sequencing results of SKOV3 cells transfected with miR-4772 mimics or inhibitor. RESULTS: According the optimal cutoff level of PD-L1 expression of 1.31582 (90th quantile), the patients were divided into high- and low-PD-L1 expression groups. A total of 840 DEGs were identified, including 549 significantly up-regulated genes and 291 down-regulated genes. Among them, 20 important DEGs were found to closely correlate with miR-4772 expression, and WGCNA analysis identified 48 weighted genes significantly correlated with miR-4772. Twelve genes were identified as both key DEGs and weighted genes and were treated as the hub genes. ssGSEA analysis showed that both the patients with high PD-L1 expressions and those with high miR-4772 expressions showed more active immune infiltration and functional activity. The 12 hub genes were involved mainly in immune-related signaling pathways, and PPI analysis suggested significant interactions among the hub genes. The two hub genes CD96 and TBX21 showed close correlation with the survival of ovarian cancer patients. The sequencing results of SKOV3 cells transfected with miR-4772 mimics or inhibitor showed that the changes in miR-4772 expression level caused obvious changes in the expressions of the 12 hub genes and PD-L1. CONCLUSION: MiR-4772 plays a regulatory role in the formation of tumor immune microenvironment in ovarian cancer by regulating 12 hub genes.

[Clinical analysis of 4 children with hereditary hypercholesterolemia].

Objective: To investigate the clinical characteristics of hereditary hypercholesterolemia in childhood. Methods: The clinical data including general conditions, clinical manifestations, laboratory tests, and genetic testing results of 4 children with hereditary hypercholesterolemia who admitted to Henan Children's Hospital from January 2020 to December 2020 were retrospectively analyzed. Results: There were 4 female children aged 5.5,1.5,6.3,3.1 years, all presented with skin xanthoxoma as the chief complaint. Plasma total cholesterol (range 11.8 to 20.9 mmol/L) and low density lipoprotein-cholesterol (range 8.2 to 13.7 mmol/L) were significantly elevated. The serum ß-glutamate levels in case 1 (241.2 µmol/L) and case 2 (164.2 µmol/L) increased significantly. Genetic analysis revealed compound heterozygous variants of ABCG8 gene in case 1 and ABCG5 gene in case 2 who were diagnosed with sitosterolemia. Case 3 and 4 who all had family history of hypercholesterolemia and compound heterozygous variants of LDLR gene were diagnosed with familial hypercholesterolemia. After diet treatment, the blood lipids returned normal and the skin xanoma subsided in case 1 and 2. In case 3 and 4, the blood lipids gradually decreased after diet and rosuvastatin treatment. Conclusions: Xanthomatosis is the common clinical manifestation of sitosterolemia and familial hypercholesterolemia. Family history, blood plant sterol profile, genetic variation, and changes in blood lipids after early dietary treatment are helpful for disease identification.

[A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city].

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.

Prediction of visual function from automatically quantified optical coherence tomography biomarkers in patients with geographic atrophy using machine learning.

Geographic atrophy (GA) is a vision-threatening manifestation of age-related macular degeneration (AMD), one of the leading causes of blindness globally. Objective, rapid, reliable, and scalable quantification of GA from optical coherence tomography (OCT) retinal scans is necessary for disease monitoring, prognostic research, and clinical endpoints for therapy development. Such automatically quantified biomarkers on OCT are likely to further elucidate structure-function correlation in GA and thus the pathophysiological mechanisms of disease development and progression. In this work, we aimed to predict visual function with machine-learning applied to automatically acquired quantitative imaging biomarkers in GA. A post-hoc analysis of data from a clinical trial and routine clinical care was conducted. A deep-learning automated segmentation model was applied on OCT scans from 476 eyes (325 patients) with GA. A separate machine learning prediction model (Random Forest) used the resultant quantitative OCT (qOCT) biomarkers to predict cross-sectional visual acuity under standard (VA) and low luminance (LLVA). The primary outcome was regression coefficient (r2) and mean absolute error (MAE) for cross-sectional VA and LLVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. OCT parameters were predictive of VA (r2 0.40 MAE 11.7 ETDRS letters) and LLVA (r2 0.25 MAE 12.1). Normalised random forest feature importance, as a measure of the predictive value of the three constituent features of GA; retinal pigment epithelium (RPE)-loss, photoreceptor degeneration (PDR), hypertransmission and their locations, was reported both on voxel-level heatmaps and ETDRS-grid subfields. The foveal region (46.5%) and RPE-loss (31.1%) had greatest predictive importance for VA. For LLVA, however, non-foveal regions (74.5%) and PDR (38.9%) were most important. In conclusion, automated qOCT biomarkers demonstrate predictive significance for VA and LLVA in GA. LLVA is itself predictive of GA progression, implying that the predictive qOCT biomarkers provided by our model are also prognostic.

Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

The morphological and histological study of chicken left ovary during growth and development among Hy-line brown layers of different ages.

Chicken ovaries are known to develop asymmetrically and only the left ovary fully develops. Although both have been greatly investigated, a gap in scientific reports is still felt between 2-mo-old and sexual maturity. In this study, we aimed at investigating the changes in components that occur during growth to analyze the morphohistological correlation between the left ovary and the follicle development at different age stages in Gallus domesticus. The ovaries were harvested from 60 chickens aged 1 and 3-wk-old, 1, 2, 3, and 4-mo-old (n = 10 per age group), then fixed in AAF solution. Hematoxylin-and Eosin protocol was used to stain the tissue for microscopic observations. Results revealed that the left ovary exhibited an ovarian tissue, a site of follicular growth that displayed various shapes from smooth to greatly indented as the follicles differentiated. Atretic follicles at various regression stages were noticed frequently as the chicks grew in age from 3-wk-old onward along with their differentiation. Rete ovarii, remnants from the male homologs were observed throughout the whole study showing epoöphoron, connecting rete, and gland-like structures that tend to diminish with age. The feature of the left ovary is closely related to the follicular developmental stage, and the bigger and differentiated the follicles are, the more indented and irregular its epithelium appears. Atresia is a normal physiological process that we observed throughout the whole study. Also that, rete ovarii do not spontaneously arise in the ovary but it develops and grows in juvenile chicken as well as in adult ones.

MicroRNA-338 in MSCs-derived exosomes inhibits cardiomyocyte apoptosis in myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) is caused by myocardial ischemia and hypoxia, which causes irreversible damage to the myocardium and seriously endangers human health. Exosomes are small, monolayer-structured extracellular vesicles that transport proteins, lipids, mRNAs, and miRNAs between cells. Mesenchymal stem cells (MSCs) can secrete a large number of exosomes and play a role in many pathophysiological processes. The purpose of this paper was to investigate the role of exosomal microRNA-338 (miR-338) in MI and its underlying mechanism of action. MATERIALS AND METHODS: We transfected rat bone marrow-derived MSCs with miR-338 mimic or negative control and extracted exosomes secreted by MSCs. Expression of miR-338 in MSCs, exosomes, and H9c2 cells co-cultured with exosomes was detected by PCR. Then, we treated H9c2 cells with H2O2. We transfected miR-338 inhibitor into H9c2 cells co-cultured with exosomes to further study the function of miR-338. Apoptosis of H9c2 cells were observed by Western blot, flow cytometry, and cell staining. We also established a MI rat model to study the function in vivo and injected exosomes in the myocardium. Seven days later, we used echocardiography to detect the heart function of rats. RESULTS: MiR-338 was upregulated in MSCs transfected with miR-338 mimic, exosomes, and H9c2 cells co-cultured with exosomes. When H9c2 cells were co-cultured with exosomes overexpressing miR-338, the expression of Bax was decreased while the expression of Bcl-2 was increased, and the apoptosis rate was also decreased as shown in flow cytometry, and the amount of caspase3 fluorescence was also decreased. Cardiac function was markedly improved after intramyocardial injection of exosomes overexpressing miR-338 in rats. It was demonstrated using computational tools, Western blot, and Luciferase reporter gene experiments that miR-338 could regulate JNK pathway via targeting MAP3K2. CONCLUSIONS: Exosomal miR-338 can inhibit cardiomyocyte apoptosis and improve cardiac function in rats with myocardial infarction by regulating MAP3K2/JNK signaling pathway.

Circulating miR-374b-5p negatively regulates osteoblast differentiation in the progression of osteoporosis via targeting Wnt3 AND Runx2.

Osteoporosis is defined as an aging-related skeletal disorder involving deterioration of bone mass and bone structure, and consequently, increased risk of fractures. Emerging evidence indicates the dysregulation of microRNAs (miRNAs) in the progression of osteoporosis. However, whether such associated miRNAs control osteoblast differentiation or constitute therapeutic targets remains elusive. In the present study, we found elevated circulating miR-374b-5p level associated with postmenopausal osteoporosis. miR-374b-5p served as a critical suppressor of osteoblast differentiation. We further identified that miR-374b-5p directly targeted Wnt family member 3 (Wnt3) and Runt-related transcription factor 2 (Runx2) through its 3'-untranslated regions (3'UTRs). Moreover, the antagonist of miR-374b-5p could promote bone formation in ovariectomy (OVX)-induced mice. Together, our results revealed that miR-374b-5p directly targeted Wnt3 and Runx2, negatively regulating osteoblast differentiation and bone formation. Collectively, circulating miR-374b-5p in the serum might serve as a potential diagnostic and therapeutic strategy for osteoporosis.

Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids.

PURPOSE: To evaluate high-dose intravenous glucocorticoid treatment on tear inflammatory cytokines and ocular surface parameters in patients with active TED. Correlations between tear inflammatory cytokines and clinical parameters were also investigated. METHODS: This prospective pilot study included 15 moderate-to-severe and active TED patients. Control group consist of 15 sex and age-matched healthy subjects. All TED patients were treated with high-dose intravenous methylprednisolone with cumulative dose of 4.5 g during the therapy subdivided into 12 weekly infusions. Tear concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) were measured by multiplex bead analysis in TED patients at baseline and 12 weeks after treatment. Ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescent staining, and Schirmer's test were obtained from TED and controls. RESULTS: All baseline cytokine levels except for IL-17A were significantly elevated in active TED patients compared with controls. Concentrations of IL-1ß, IL-6, IL-8, TNF-α, and VEGF were significantly decreased at 12 weeks compared with baseline. OSDI and TBUT showed significant improvement at 6 and 12 weeks. There were significant positive correlations between IL-6, IL-8, and CAS, and negative correlation was found between IL-6 level and TED duration before methylprednisolone treatment. The reduction of IL-6, IL-8, and VEGF were positive correlated with the reduction in CAS at 12 weeks. CONCLUSIONS: High-dose glucocorticoids treatment improved ocular surface symptom, increased the tear film stability, and decreased tear inflammatory cytokines in active TED. The reduction of the inflammatory cytokines is consistent with the improvement of clinical parameters.

Identification of genetic loci associated with growth traits at weaning in yak through a genome-wide association study.

A multilocus GWAS was performed to explore the genetic architecture of four growth traits in yak. In total, 354 female yaks for which measurements of body weight (BW), withers height (WH), body length (BL) and chest girth (CG) at weaning were available underwent genotyping with the Illumina BovineHD BeadChip (770K). After quality control, we retained 98 688 SNPs and 354 animals for GWAS analysis. We identified seven, 18, seven and nine SNPs (corresponding to seven, 17, seven and eight candidate genes) associated with BW, WH, BL and CG at weaning respectively. Interestingly, most of these candidate genes were reported to be involved in growth-related processes such as muscle formation, lipid deposition, feed efficiency, carcass composition and development of the central and peripheral nervous system. Our results offer novel insight into the molecular architecture underpinning yak growth traits. Further functional analyses are thus warranted to explore the molecular mechanisms whereby these genes affect these traits of interest.

The effect of SOX9 on islet ß cells in high glucose environment through regulation of ERK/P38 signaling pathway.

OBJECTIVE: Islet beta cells are involved in insulin secretion. SRY-related high mobility group 9 (SX-S9) is involved in the progression of various diseases, but the role of SOX9 in islet ß cells remains unclear. PATIENTS AND METHODS: The islet ß cell MIN6 cells were cultured in vitro and randomly divided into control group, high glucose group, and SOX9 siRNA group followed by analysis of SOX9 mRNA and protein expression by real-time PCR and Western blot, respectively, cell proliferation by MTT assay, cell apoptosis by flow cytometry, secretion of inflammatory factors TNF-α and IL-2 by ELISA, insulin secretion levels by spectrophotometer, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, as well as ERK/P38 signaling protein expression by Western blot. RESULTS: Under high glucose environment, SOX9 mRNA and protein expression were significantly increased, MIN6 cell proliferation was inhibited, apoptosis rate and secretion of TNF-α and IL-2 were increased, along with decreased insulin secretion, increased MPO content, decreased SOD activity and phosphorylation of ERK/P38, compared with control group (p < 0.05). However, transfection of SOX9 siRNA reduced SOX9 expression, promoted proliferation of MIN6 cells, decreased apoptotic rate and secretion of TNF-α and IL-2, increased insulin secretion, decreased MPO content, increased SOD and ERK/P38 protein phosphorylation. Compared with high glucose group, the differences were statistically significant (p < 0.05). CONCLUSIONS: The expression of SOX9 is increased under high glucose environment. Down-regulation of SOX9 expression can inhibit islet cell apoptosis, oxidative stress and inflammation, and promote islet cell proliferation and insulin secretion by regulating ERK/P38 signaling pathway.