Comprehensive analysis of the expression profiles of mRNA, lncRNA, circRNA, and miRNA in primary hair follicles of coarse sheep fetal skin.

BACKGROUND: The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive. RESULTS: A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-ß, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir's role in the ceRNA regulatory network mechanism, we identified 113 circRNA-miRNA pairs and 14 miRNA-mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1. CONCLUSIONS: Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed.

Preparation of polyclonal antibodies against the Drosophila deacetylases SIRT 6 and SIRT 7.

SIRT6 and SIRT7, as members of the Sirtuins family, are indispensable for the growth and development of Drosophila. They play crucial roles in maintaining genome stability, regulating metabolic senescence, and controlling tumorigenesis. To investigate their involvement in the Drosophila life cycle, we focused on describing the expression and purification of recombinant Drosophila SIRT6 and SIRT7 proteins. Subsequently, these proteins were utilized for generating polyclonal antibodies against Drosophila SIRT6 and SIRT7. The recombinant expression plasmid was introduced into E. coli cells to enable the production of SIRT6 and SIRT7 proteins. Following immunizations of New Zealand white rabbits and guinea pigs with the recombinant proteins as antigens, specific polyclonal antisera against both proteins were obtained. After purification, the specificity of SIRT6 and SIRT7 was confirmed using ELISA and western blot analyses, demonstrating strong specificity. These antibodies hold promise for the development of detection assays required for further research.

VO2max (VO2peak) in elite athletes under high-intensity interval training: A meta-analysis.

Consensus is lacking regarding whether high-intensity interval training (HIIT) effectively improves VO2max (VO2peak) in elite athletes (Athlete must be involved in regular competition at the national level). This meta-analysis compared the effects of HIIT and conventional training methods (continuous training, repeated-sprint training, high volume low-intensity training, high-intensity continuous running, sprint-interval training, moderate-intensity continuous training)on VO2max in elite athletes. Nine studies were included, comprising 176 elite athletes (80 female). Compared to that with conventional training, VO2max was significantly increased after HIIT (overall: 0.58 [0.30, 0.87], I2 = 0.49, P = 0.03; males: 0.41 [0.06, 0.76], I2 = 0%, P = 0.89). VO2max had positive training effects when the HIIT recovery period had an interval time ≥2 min (0.44 [0.03, 0.84], I2 = 0%, P = 0.99) and recovery phase intensity ≤40% (0.38 [0.05, 0.71], I2 = 0%, P = 0.96). Thus, HIIT shows superiority over conventional training methods in improving VO2max, promoting aerobic capacity, in elite athletes.

Meta-analysis of the efficacy of probiotics to treat diarrhea.

BACKGROUND: To collect the published trials of probiotics in the treatment of diarrhea and to strictly evaluate and systematically analyze the efficacy of probiotics use for the prevention and treatment of patients with diarrhea. METHODS: We searched domestic and foreign literature published between January 2016 and July 2022 to find randomized control trials that used probiotics to treat diarrhea. Only studies published in English were considered. The quality of the included literatures was assessed by using the methods provided in the Cochrane Handbook. Valid data were extracted and analyzed by meta- analysis using the Software RevMan5.2. RESULTS: Total 16 trials and 1585 patients were included. The results of the meta- analysis showed that in comparison with the simple Western medicine treatment group or placebo, the added use of probiotics could improve stool frequency, stool morphology, and related irritable bowel syndrome symptoms. CONCLUSION: The added use of probiotics can further improve clinical outcomes in the patients with diarrhea; however, the implementation of larger and higher quality clinical trials is necessary to verify this conclusion.

Will intestinal flora therapy become a new target in type-2 diabetes mellitus? A review based on 13 clinical trials.

Introduction: Background: diabetes mellitus (DM) is a chronic disease and its pathogenesis is still inconclusive. Current evidence suggests an association between intestinal flora and type-2 diabetes mellitus (T2DM). In this paper, we summarized the current research, determining whether intestinal flora may become a new method to treat T2DM, and providing a theoretical basis and literature references for the prevention of T2DM based on the regulation of intestinal flora. Method: we carried out a review based on 13 published clinical trials to determine the correlation between T2DM and intestinal flora, and between changes in clinical outcomes and in intestinal flora in the development of T2DM; to assess the pathological mechanisms; and to discuss the treatment of diabetes based on intestinal flora. Results: we found that intestinal flora is involved in the occurrence and development of T2DM. Several pathological mechanisms may be involved in the process, including improving the gut barrier, alleviating inflammation, increasing glucagon-like peptide (GLP) 1 and GLP 2, increasing the production of short-chain fatty acids (SCFAs), and so on. Several measures based on intestinal flora, including exercise, food, specific diets, drugs and probiotics, would be used to treat and even prevent T2DM. Conclusions: high-quality studies are required to better understand the clinical effects of intestinal flora in T2DM.

Introducción: Antecedentes: la diabetes mellitus (DM) es una enfermedad crónica cuya patogénesis no está clara. La evidencia actual sugiere una asociación entre la flora intestinal y la diabetes mellitus de tipo 2 (DMT2). Este artículo revisa la investigación actual para determinar si la flora intestinal puede ser un nuevo método de tratamiento de la DMT2. Métodos: se revisaron 13 ensayos clínicos publicados para determinar la correlación entre la DMT2 y la flora intestinal, cambios en los resultados clínicos y en la flora intestinal durante el desarrollo de la DMT2; para resumir su mecanismo patogénico; y, desde el punto de vista de la flora intestinal, para explorar el tratamiento de la diabetes. Resultados: se encontró que la flora intestinal estaba involucrada en el desarrollo de la DMT2. Este proceso puede implicar una variedad de mecanismos patológicos: mejora de la barrera intestinal, reducción de la inflamación, aumento del péptido similar al glucagón (GLP) 1 y GLP 2, y el del rendimiento de los ácidos grasos de cadena corta. Algunas medidas basadas en la flora intestinal, como el ejercicio, los alimentos, las dietas especiales, los medicamentos y los probióticos, se utilizarán para tratar e incluso prevenir la DMT2. Conclusión: se necesitan estudios de alta calidad para comprender mejor los efectos clínicos de la flora intestinal en los pacientes con DMT2.

An Improved Timed Elastic Band (TEB) Algorithm of Autonomous Ground Vehicle (AGV) in Complex Environment.

In recent decades, the Timed Elastic Band (TEB) algorithm is widely used for the AGV local path panning because of its convenient and efficiency. However, it may make a local detour when encountering a curve turn and cause excessive energy consumption. To solve this problem, this paper proposed an improved TEB algorithm to make the AGV walk along the wall when turning, which shortens the planning time and saves energy. Experiments were implemented in the Rviz visualization tool platform of the robot operating system (ROS). Simulated experiment results reflect that an amount of 5% reduction in the planning time has been achieved and the velocity curve implies that the operation was relatively smooth. Practical experiment results demonstrate the effectiveness and feasibility of the proposed method that the robots can avoid obstacles smoothly in the unknown static and dynamic obstacle environment.

A Hypoxia Signature for Predicting Prognosis and Tumor Immune Microenvironment in Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with dismal prognosis. Hypoxia is one of characteristics of cancer leading to tumor progression. For ACC, however, no reliable prognostic signature on the basis of hypoxia genes has been built. Our study aimed to develop a hypoxia-associated gene signature in ACC. Data of ACC patients were obtained from TCGA and GEO databases. The genes included in hypoxia risk signature were identified using the Cox regression analysis as well as LASSO regression analysis. GSEA was applied to discover the enriched gene sets. To detect a possible connection between the gene signature and immune cells, the CIBERSORT technique was applied. In ACC, the hypoxia signature including three genes (CCNA2, COL5A1, and EFNA3) was built to predict prognosis and reflect the immune microenvironment. Patients with high-risk scores tended to have a poor prognosis. According to the multivariate regression analysis, the hypoxia signature could be served as an independent indicator in ACC patients. GSEA demonstrated that gene sets linked to cancer proliferation and cell cycle were differentially enriched in high-risk classes. Additionally, we found that PDL1 and CTLA4 expression were significantly lower in the high-risk group than in the low-risk group, and resting NK cells displayed a significant increase in the high-risk group. In summary, the hypoxia risk signature created in our study might predict prognosis and evaluate the tumor immune microenvironment for ACC.

Assessment of the Quality Management System for Clinical Nutrition in Jiangsu: Survey Study.

BACKGROUND: An electronic system that automatically collects medical information can realize timely monitoring of patient health and improve the effectiveness and accuracy of medical treatment. To our knowledge, the application of artificial intelligence (AI) in medical service quality assessment has been minimally evaluated, especially for clinical nutrition departments in China. From the perspective of medical ethics, patient safety comes before any other factors within health science, and this responsibility belongs to the quality management system (QMS) within medical institutions. OBJECTIVE: This study aims to evaluate the QMS for clinical nutrition in Jiangsu, monitor its performance in quality assessment and human resource management from a nutrition aspect, and investigate the application and development of AI in medical quality control. METHODS: The participants for this study were the staff of 70 clinical nutrition departments of the tertiary hospitals in Jiangsu Province, China. These departments are all members of the Quality Management System of Clinical Nutrition in Jiangsu (QMSNJ). An online survey was conducted on all 341 employees within all clinical nutrition departments based on the staff information from the surveyed medical institutions. The questionnaire contains five sections, and the data analysis and AI evaluation were focused on human resource information. RESULTS: A total of 330 questionnaires were collected, with a response rate of 96.77% (330/341). A QMS for clinical nutrition was built for clinical nutrition departments in Jiangsu and achieved its target of human resource improvements, especially among dietitians. The growing number of participating departments (an increase of 42.8% from 2018 to 2020) and the significant growth of dietitians (t93.4=-0.42; P=.02) both show the advancements of the QMSNJ. CONCLUSIONS: As the first innovation of an online platform for quality management in Jiangsu, the Jiangsu Province Clinical Nutrition Management Platform was successfully implemented as a QMS for this study. This multidimensional electronic system can help the QMSNJ and clinical nutrition departments achieve quality assessment from various aspects so as to realize the continuous improvement of clinical nutrition. The use of an online platform and AI technology for quality assessment is worth recommending and promoting in the future.

Identification of a Ferroptosis-Related Signature Associated with Prognosis and Immune Infiltration in Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignant tumor with poor prognosis. Ferroptosis, a new form of cell death, differs from other forms of cell death and plays a vital role in tumor progress. Our study aimed to establish a ferroptosis-related signature with prognostic value in ACC. RNA-seq data and corresponding clinical characteristics for ACC were downloaded from TCGA and GEO databases. Genes included in ferroptosis risk signature were assessed by univariable and multivariable Cox regression analysis as well as lasso regression analysis. The prognostic value of the ferroptosis risk signature was assessed using K-M and ROC curves. Furthermore, we performed GSEA to discover the enriched gene sets in high-risk group. Additionally, TIMER website was applied to detect a possible connection between the signature and immune cells infiltration. ssGSEA was performed to evaluate scores of immune cells and immune-related pathways in two groups. A ferroptosis signature comprised of six genes (SLC7A11, TP53, HELLS, ACSL4, PCBP2, and HMGB1) was constructed to predict prognosis and reflect the immune infiltration in ACC. Patients in high-risk group were inclined to have worse prognosis. The ferroptosis model performed well in predicting prognosis and could be served as an independent indicator in ACC. GSEA revealed that gene sets correlated with biological processes including cell cycle, DNA replication, base excision repair, and P53 signaling pathway were highly enriched in high-risk group. In addition, we discovered that the expressional levels of hub genes were linked to six immune cells' infiltration in ACC tumor. ssGSEA revealed that contents of most immune cells significantly decreased in the high-risk group. In conclusion, the novel ferroptosis risk signature could be useful in predicting prognosis and reflecting immune infiltration in ACC. It also brings us new insights into the possible value of targeting ferroptosis during the therapy of ACC.

A new multi-scale backbone network for object detection based on asymmetric convolutions.

Real-time object detection on mobile platforms is a crucial but challenging computer vision task. However, it is widely recognized that although the lightweight object detectors have a high detection speed, the detection accuracy is relatively low. In order to improve detecting accuracy, it is beneficial to extract complete multi-scale image features in visual cognitive tasks. Asymmetric convolutions have a useful quality, that is, they have different aspect ratios, which can be used to exact image features of objects, especially objects with multi-scale characteristics. In this paper, we exploit three different asymmetric convolutions in parallel and propose a new multi-scale asymmetric convolution unit, namely MAC block to enhance multi-scale representation ability of CNNs. In addition, MAC block can adaptively merge the features with different scales by allocating learnable weighted parameters to three different asymmetric convolution branches. The proposed MAC blocks can be inserted into the state-of-the-art backbone such as ResNet-50 to form a new multi-scale backbone network of object detectors. To evaluate the performance of MAC block, we conduct experiments on CIFAR-100, PASCAL VOC 2007, PASCAL VOC 2012 and MS COCO 2014 datasets. Experimental results show that the detection precision can be greatly improved while a fast detection speed is guaranteed as well.

Deep Learning-Based Imbalanced Classification With Fuzzy Support Vector Machine.

Imbalanced classification is widespread in the fields of medical diagnosis, biomedicine, smart city and Internet of Things. The imbalance of data distribution makes traditional classification methods more biased towards majority classes and ignores the importance of minority class. It makes the traditional classification methods ineffective in imbalanced classification. In this paper, a novel imbalance classification method based on deep learning and fuzzy support vector machine is proposed and named as DFSVM. DFSVM first uses a deep neural network to obtain an embedding representation of the data. This deep neural network is trained by using triplet loss to enhance similarities within classes and differences between classes. To alleviate the effects of imbalanced data distribution, oversampling is performed in the embedding space of the data. In this paper, we use an oversampling method based on feature and center distance, which can obtain more diverse new samples and prevent overfitting. To enhance the impact of minority class, we use a fuzzy support vector machine (FSVM) based on cost-sensitive learning as the final classifier. FSVM assigns a higher misclassification cost to minority class samples to improve the classification quality. Experiments were performed on multiple biological datasets and real-world datasets. The experimental results show that DFSVM has achieved promising classification performance.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition).

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Duodenal-Jejunal Exclusion Surgery Improves Type 2 Diabetes in a Rat Model Through Regulation of Early Glucose Metabolism.

OBJECTIVES: Metabolic surgery has been proven to be widely effective for the control of glucose and weight in patients with type 2 diabetes and obesity. However, the effects of bariatric surgery on nonobesity type 2 diabetes and its metabolism are still unclear. This study aimed to measure the effects of duodenal-jejunal exclusion on glycometabolism in nonobese rats with type 2 diabetes and to investigate its mechanisms. METHODS: Goto-Kakizaki rats and Sprague-Dawley rats were divided into duodenal-jejunal exclusion operation groups and sham operation groups, respectively. The glucose-relative parameters were measured before and after operation. Eight weeks postoperation, the levels of the key regulators of intestinal gluconeogenesis and the crucial proteins of hepatic insulin signalling were evaluated. RESULTS: Postoperatively, the concentrations of blood glucose declined, and the insulin sensitivity increased significantly in rats with diabetes. However, there was no obvious reduction in weight. Eight weeks postoperatively, the mRNA levels of glucose-6-phosphatase and phosphoenolpyruvate pyruvate kinase in the jejunum and the levels of insulin receptor substrate-2 and glucose transporter-2 in the liver were significantly increased compared with the rats that had undergone the sham operation. CONCLUSIONS: Duodenal-jejunal exclusion surgery is an effective procedure for improving glucose metabolism independent of weight loss in nonobese rats with diabetes. The molecular mechanisms might be associated with a series of processes, including intestinal gluconeogenesis and the hepatic insulin signaling pathway.

Adiposity is not beneficial to bone mineral density in 0-5 year old Chinese children: The Jiangsu bone health study.

OBJECTIVE: Data on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD. SUBJECTS AND METHODS: This was a large population-based multicenter study in which the representative children aged 0-5 years were recruited from 13 Children's Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson's correlation and further tested using partial correlation in the additive model. RESULTS: A total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r=0.711, P<0.001; r=0.727, P<0.001; r=-0.318, P<0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2kg, but started to gain slowlyand even decreased when the weight was over 21.2kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P<0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (ß=-47.45, 95%CI=-85.07, -9.83, P=0.013). CONCLUSIONS: Adiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.

A Predictive Model to Distinguish Papillary Thyroid Carcinomas from Benign Thyroid Nodules Using Ultrasonographic Features: A Single-Center, Retrospective Analysis.

BACKGROUND We developed a model based on ultrasound (US) features of thyroid nodules and cervical lymph nodes to distinguish papillary thyroid carcinomas (PTC) from benign thyroid nodules. MATERIAL AND METHODS We retrospectively collected data on preoperative ultrasonographic characteristics and postoperative histological data from 1119 patients who underwent thyroidectomy in our center from January 2017 to January 2018. Variables of age, sex, and US features of thyroid nodule and lymph nodes features were analyzed. A logistic regression model was established for PTC prediction. RESULTS Logistic regression analysis confirmed that age under 45 years (OR=2.22, p=0.00), hypoechogenicity (OR=3.70, p=0.00), irregular shape (OR=2.13, p=0.004), ill-defined margin (OR=2.26, p=0.08), spiculate margin (OR=3.30, p=0.00), indefinite border (OR=2.45, p=0.00), capsular invasion (OR=7.76, p=0.006), taller-than-wide shape (OR=2.94, p=0.00), solid structure (OR=2.46, p=0.001), microcalcifications (OR=3.92, p=0.00), coexistence of microcalcifications and macrocalcifications (OR=5.84, p=0.006), and central vascularity (OR=2.10, p=0.001) were independently associated with increased risks for PTC, as well as lymph nodes metastasis features (absence of an echogenic hilum [OR=3.74, p=0.027] and increased vascularization [OR=3.55, p=0.086]). The area under the curve (AUC) for the risk score diagnosis system was 0.916. CONCLUSIONS This predictive model is a reliable, simple, and cost-effective diagnostic tool for PTC.

Real-Time Docking Ring Detection Based on the Geometrical Shape for an On-Orbit Spacecraft.

Docking ring is a circular hatch of spacecraft that allows servicing spacecraft to dock in various space missions. The detection of the ring is greatly beneficial to automatic capture, rendezvous and docking. Based on its geometrical shape, we propose a real-time docking ring detection method for on-orbit spacecraft. Firstly, we extract arcs from the edge mask and classify them into four classes according to edge direction and convexity. By developing the arc selection strategy, we select a combination of arcs possibly belonging to the same ellipse, and then estimate its parameters via the least squares fitting technique. Candidate ellipses are validated according to the fitness of the estimation with the actual edge pixels. The experiments show that our method is superior to the state-of-the-art methods, and can be used in real time application. The method can also be extended to other applications.

The Diagnostic Performance of Afirma Gene Expression Classifier for the Indeterminate Thyroid Nodules: A Meta-Analysis.

BACKGROUND: Approximately 15 to 30% of thyroid nodules evaluated by fine-needle aspiration (FNA) were classified as indeterminate; the accurate diagnostic molecular tests of these nodules remain a challenge. We aimed to evaluate the diagnostic performance of Afirma gene expression classifier (GEC) for the indeterminate thyroid nodules (ITNs). METHODS: Studies published from January 2005 to December 2018 were systematically reviewed. The gold reference standard relied on the histopathologic results diagnosis from thyroidectomy surgical specimens. MetaDisc software was used to investigate the pooled sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves. RESULTS: A total of 18 studies involving 5290 patients with 3290 cases of ITNs were included. Collected data revealed that the pooled sensitivity of GEC was 95.5% (95% CI 93.3%-97.0%, p < 0.001), the specificity was 22.1% (95% CI 19.4%-24.9%, p < 0.001), the NPV was 88.2% (95% CI 0.833-0.921, p < 0.001), the PPV was 44.3% (95% CI 0.416-0.471, p < 0.001), and the DOR was 5.25 (95% CI 3.42-8.04, p= 0.855). CONCLUSION: The GEC has quite high sensitivity of 95.5% but low specificity of 22.1%. The high sensitivity makes it probable to rule out malignant nodules. Thus, over half of nodules with GEC-suspicious results still require further validation like molecular markers, diagnostic surgery, or long follow-up, which limits its use in future clinical practice.

The Adverse Effects of Thyrotropin Absence on Pancreatic ß Cell Function in Mice.

Thyrotropin (TSH) is a modulator of glucose metabolism by binding to its receptor on pancreatic cells. We used thyrotropin receptor (TSHR) knockout mice (Tshr -/-) as a model of TSH deletion to study its function in pancreatic ß cells. Tshr -/- mice had a similar body weight at birth compared with Tshr +/+ mice, but grew at a significantly slower rate until adulthood with adequate thyroxine supplementation. TSH deletion led to lower fasting and postprandial blood glucose, insulin secretion impairment, and atrophy of islets in adult mice. Transcription factors and markers of pancreatic ß cell maturation, Pdx1, Nkx6.1, Glut2, and insulin, together with cell proliferation marker Ki67 showed no differences at the mRNA level between the two groups. However, the Bax/Bcl-2 ratio was remarkably elevated in Tshr -/- mice at both mRNA and protein levels. We hypothesized that pancreatic cell apoptosis, rather than abnormal cell proliferation and maturation, is associated with pancreatic dysfunction and glucose intolerance in the absence of TSH modulation.

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

E2F8, a direct target of miR-144, promotes papillary thyroid cancer progression via regulating cell cycle.

BACKGROUND: Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. METHODS: E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144. RESULTS: E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression. CONCLUSIONS: Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy. TRIAL REGISTRATION: No applicable.