Highly Reversible Zn-Air Batteries Enabled by Tuned Valence Electron and Steric Hindrance on Atomic Fe-N4-C Sites.

The bifunctional oxygen electrocatalyst is the Achilles' heel of achieving robust reversible Zn-air batteries (ZABs). Herein, durable bifunctional oxygen electrocatalysis in alkaline media is realized on atomic Fe-N4-C sites reinforced by NixCo3-xO4 (NixCo3-xO4@Fe1/NC). Compared with that of pristine Fe1/NC, the stability of the oxygen evolution reaction (OER) is increased 10 times and the oxygen reduction reaction (ORR) performance is also improved. The steric hindrance alters the valence electron at the Fe-N4-C sites, resulting in a shorter Fe-N bond and enhanced stability of the Fe-N4-C sites. The corresponding solid-state ZABs exhibit an ultralong lifespan (>460 h at 5 mA cm-2) and high rate performance (from 2 to 50 mA cm-2). Furthermore, the structural evolution of NixCo3-xO4@Fe1/NC before and after the OER and ORR as well as charge-discharge cycling is explored. This work develops an efficient strategy for improving bifunctional oxygen electrocatalysis and possibly other processes.

Gasless Single-Incision Endoscopic Surgery via Subclavicular Approach for Lateral Neck Dissection in Patients with Papillary Thyroid Cancer.

BACKGROUND: The technical difficulties and trauma of remote access methods in endoscopic surgery (ES) for lateral neck dissection (LND) can be daunting for most patients with papillary thyroid cancer (PTC) and surgeons. The purpose of study was to introduce gasless single-incision ES via a subclavicular approach (ESSA) and to explore its safety and efficacy for LND. METHODS: Between January 2022 and February 2023, we retrospectively reviewed 17 patients with PTC who underwent ESSA for LND. In addition, 22 patients who received video-assisted ES (VAES) and 48 patients who underwent open surgery (OP) for LND during the same period were included. Clinicopathological characteristics, complications, and efficacy of the lymph node yield (LNY) were compared between the ESSA and the other two groups (VAES and OP). RESULTS: The LNY from central and lateral neck dissection by ESSA was comparable to that by VAES (9.2 ± 8.1 vs. 9.5 ± 4.2, P = 0.986, and 33.5 ± 11.6 vs. 30.6 ± 9.2, P = 0.382, respectively) and OP (9.2 ± 8.1 vs. 11.0 ± 5.4, P = 0.420, and 33.5 ± 11.6 vs. 31.5 ± 7.9, P = 0.383, respectively). Swallowing impairment scores at 1 and 3 months were significantly lower after ESSA than those after VAES (1.8 ± 1.0 vs. 3.0 ± 1.2, P = 0.003, and 0.9 ± 0.8 vs. 1.7 ± 0.8, P = 0.006, respectively). The cosmetic satisfaction rate 1 month after surgery was significantly higher in the ESSA group than that in the VAES group (100 vs. 31.8%, P < 0.001). CONCLUSIONS: ESSA is a safe and minimally invasive procedure that provides a scarless cervical appearance and has good efficacy for LND. Therefore, ESSA may be a feasible choice for selected patients with N1b PTC with cervical cosmetic needs.

US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Tanshinone IIA alleviates bleomycin-induced pulmonary fibrosis by inhibiting Zbtb16.

Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro. Meanwhile, the protein content of TGF-ß1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-ß1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-ß/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.

Anomaly Detection of Permanent Magnet Synchronous Motor Based on Improved DWT-CNN Multi-Current Fusion.

The Permanent Magnet Synchronous Motor (PMSM) is the power source maintaining the stable and efficient operation of various pieces of equipment; hence, its reliability is crucial to the safety of public equipment. Convolutional Neural Network (CNN) models face challenges in extracting features from PMSM current data. A new Discrete Wavelet Transform Convolutional Neural Networks (DW-CNN) feature with fusion weight updating Long Short-Term Memory (LSTM) anomaly detection is proposed in this paper. This approach combines Discrete Wavelet Transform (DWT) with high and low-frequency separation processing and LSTM. The anomaly detection method adopts DWT and CNN by separating high and low-frequency processing. Moreover, this method combines the hybrid attention mechanism to extract the multi-current signal features and detects anomalies based on weight updating the LSTM network. Experiments on the motor bearing real fault dataset and the PMSM stator fault dataset prove the method's strong capability in fusing current features and detecting anomalies.

Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease.

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N6-methyladenosine (m6A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m6A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy.

Artificial intelligence-based prediction of cervical lymph node metastasis in papillary thyroid cancer with CT.

OBJECTIVES: To develop an artificial intelligence (AI) system for predicting cervical lymph node metastasis (CLNM) preoperatively in patients with papillary thyroid cancer (PTC) based on CT images. METHODS: This multicenter retrospective study included the preoperative CT of PTC patients who were divided into the development, internal, and external test sets. The region of interest of the primary tumor was outlined manually on the CT images by a radiologist who has eight years of experience. With the use of the CT images and lesions masks, the deep learning (DL) signature was developed by the DenseNet combined with convolutional block attention module. One-way analysis of variance and least absolute shrinkage and selection operator were used to select features, and a support vector machine was used to construct the radiomics signature. Random forest was used to combine the DL, radiomics, and clinical signature to perform the final prediction. The receiver operating characteristic curve, sensitivity, specificity, and accuracy were used by two radiologists (R1 and R2) to evaluate and compare the AI system. RESULTS: For the internal and external test set, the AI system achieved excellent performance with AUCs of 0.84 and 0.81, higher than the DL (p = .03, .82), radiomics (p < .001, .04), and clinical model (p < .001, .006). With the aid of the AI system, the specificities of radiologists were improved by 9% and 15% for R1 and 13% and 9% for R2, respectively. CONCLUSIONS: The AI system can help predict CLNM in patients with PTC, and the radiologists' performance improved with AI assistance. CLINICAL RELEVANCE STATEMENT: This study developed an AI system for preoperative prediction of CLNM in PTC patients based on CT images, and the radiologists' performance improved with AI assistance, which could improve the effectiveness of individual clinical decision-making. KEY POINTS: • This multicenter retrospective study showed that the preoperative CT image-based AI system has the potential for predicting the CLNM of PTC. • The AI system was superior to the radiomics and clinical model in predicting the CLNM of PTC. • The radiologists' diagnostic performance improved when they received the AI system assistance.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

Advances in coastal ocean boundary layer detection technology and equipment in China.

Accurate and comprehensive knowledge of the atmospheric environment and its evolution within the coastal ocean boundary layer are necessary for understanding the sources, chemical mechanisms, and transport processes of air pollution in land, sea, and atmosphere. We present an overview of coastal ocean boundary layer detection technology and equipment in China and summarize the progress and main achievements in recent years. China has developed a series of coastal ocean boundary layer detection technologies, including Light Detection and Ranging (LIDAR), turbulent exchange analyzer, air-sea flux analyzer, stereoscopic remote sensing of air pollutants, and oceanic aerosol detection equipment to address the technical bottleneck caused by harsh environmental conditions in coastal ocean regions. Advances in these technologies and equipment have provided scientific assistance for addressing air pollution issues and understanding land-sea-atmosphere interactions over coastal ocean regions in China. In the future, routine atmospheric observations should cover the coastal ocean boundary layer of China.

Ligustrazine Attenuates Liver Fibrosis by Targeting miR-145 Mediated Transforming Growth Factor-ß/Smad Signaling in an Animal Model of Biliary Atresia.

To investigate therapeutic target for ligustrazine during liver fibrosis in an ethanol-induced biliary atresia rat model and transforming growth factor-ß (TGF-ß) induced hepatic stellate cell activation cell model, and the underlying mechanism, a total of 30 rats were randomly assigned into five groups (n = 6 per group): control, sham, ethanol-induced biliary atresia model, model plus pirfenidone, and model plus ligustrazine groups. The liver changes were assessed using H&E and Masson staining and transmission electron microscopy. Expression of miR-145 and mRNA and protein levels of TGF-ß/smads pathway-related proteins were detected. HSC-T6 cells were infected with LV-miR or rLV-miR-145 in the presence or absence of SMAD3 inhibitor SIS3 and treated with 2.5 ng/ml TGF-ß1 and then with ligustrazine. Collected cells were subjected to detect the expression of miR-145 and mRNA and protein expression levels of TGF-ß/smads pathway-related proteins. Ligustrazine rescued liver fibrogenesis and pathology for ethanol-caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Further experiments showed that ligustrazine inhibited intrinsic and phosphorylated Smad2/3 protein expression and modification. Similar results were obtained in cells. In addition, ligustrazine altered miR-145 expression in both animal and cell models. Lentivirus mediated miR-145 overexpression and knockdown recombinant virus showed that miR-145 enhanced the TGF-ß/Smad pathway, which led to hepatic stellate cell activation, and ligustrazine blocked this activation. This work validated that ligustrazine-regulated miR-145 mediated TGF-ß/Smad signaling to inhibit the progression of liver fibrosis in a biliary atresia rat model and provided a new therapeutic strategy for liver fibrosis. SIGNIFICANCE STATEMENT: With an ethanol-induced biliary atresia rat model, ligustrazine was found to rescue liver fibrogenesis and pathology for ethanol caused bile duct injury, revealed by decreased α-smooth muscle actin and collagen I expression and liver tissue and cell morphology integrity. Furthermore, we found ligustrazine upregulated miR-145 expression and inhibited TGF-ß/SMAD signaling pathway both in vivo and in vitro. In addition, overexpression and knockdown of miR-145 confirmed that miR-145 is involved in the ligustrazine inhibition of liver fibrosis through the TGF-ß/SMAD signaling pathway.

Estimation of turbulence parameters in the atmospheric boundary layer of the Bohai Sea, China, by coherent Doppler lidar and mesoscale model.

Obtaining turbulence parameters in the marine atmospheric boundary layer (MABL) is limited by the observation environment and cost. Therefore, estimating based on the weather forecast model or combining the model output with limited observations is a more flexible choice. We conducted cruise observation experiments in the Bohai Sea, China, from May 17 to June 4, 2021. On the basis of the wind profile observed by the coherent Doppler lidar and the temperature, as well as pressure profiles output by the Weather Research and Forecasting (WRF) model, we implemented the Tatarskii turbulence model to estimate the refractive index structure constant C n2 in the atmospheric boundary layer of the Bohai Sea under clear sky. The temporal and spatial variations of turbulence in the Bohai Sea atmospheric boundary layer are studied by combining the vertical velocity variance σ w2, skewness Ske and kurtosis Kur. The performance of simulated C n2 and meteorological parameters in the WRF in the atmospheric boundary layer at the Bohai Sea is evaluated through the experimental measurements of UAV-borne (unmanned aerial vehicle) radiosonde and lidar. Finally, we give the model of the C n2 variation with height in the atmospheric boundary layer at the Bohai Sea. The results show that WRF can better simulate C n2 in most cases. The bias between the measured and simulated C n2 is within one order of magnitude, and the root mean square error ( RMSE ) is within two orders of magnitude. Due to the potential uncertainty of the WRF, the RMSE between the measured and simulated wind speed is 4 ms-1 to 6 ms-1, which is almost two times of the result in previous studies on the underlying land surface. The overall changes of C n2 and σ w2 are similar when the turbulence is well mixed and developed, which shows the consistency in both of optical and dynamics turbulence. But this consistency is not absolute. The temperature difference between the sea surface and the atmosphere leads to the widespread existence of an inversion layer from the sea surface to hundreds of meters in the Bohai Sea. The suppression of the inversion layer weakens the near sea surface turbulence. There is an enhancement of turbulence intensity below the inversion layer and a decrease from the upper inversion layer to top of the boundary layer among the entire boundary layer, also, the position of the inflection point is determined by the height of top of the inversion layer. The main results of this study are the reference significance for further understanding the development and change characteristics of turbulence in the MABL.

A high performance nanocomposite based bioanode for biofuel cell and biosensor application.

Herein, to improve the current density and sensitivity for biofuel cell and glucose sensing application, a bioanode based on redox polymer (PEI-Fc) binding polydopamine (PDA) coated MWCNTs (PEI-Fc/PDA/MWCNTs) nanocomposite and glucose oxidase (GOD) was fabricated. PDA/MWCNTs nanocomposite was prepared by spontaneous self-polymerization of dopamine on MWCNTs surface and the PEI-Fc/PDA/MWCNTs nanocomposite was prepared by a simple self-assembly method. The PEI-Fc/PDA/MWCNTs nanocomposite and the resulting bioanode were fully characterized. A maximum current density of 0.73 mA cm-2 at the resulting bioanode was obtained by linear sweep voltammetry (LSV) at the scan rate of 50 mV s-1 with 20 mM glucose concentration. Moreover, a linear range up to 4 mM, a high sensitivity of 57.2 µA mM-1 cm-2, a fast response time reaching 95% of the steady current (2 s) and a low limit of detection (0.024 mM) were achieved. The amperometric method demonstrated both the sensitivity and the stability of the bioanode for glucose-sensing was improved by the employed PDA layer. Finally, the biosensor was used for glucose detection in human serum samples showing good recoveries. This study proposed an excellent functional material prepared by a facile self-assembled method for applying in biofuel cells and second-generation biosensors.

Improving PM2.5 Forecasts in China Using an Initial Error Transport Model.

Efforts of using data assimilation to improve PM2.5 forecasts have been hindered by the limited number of species and incomplete vertical coverage in the observations. The common practice of initializing a chemical transport model (CTM) with assimilated initial conditions (ICs) may lead to model imbalances, which could confine the impacts of assimilated ICs within a day. To address this challenge, we introduce an initial error transport model (IETM) approach to improving PM2.5 forecasts. The model describes the transport of initial errors by advection, diffusion, and decay processes and calculates the impacts of assimilated ICs separately from the CTM. The CTM forecasts with unassimilated ICs are then corrected by the IETM output. We implement our method to improve PM2.5 forecasts over central and eastern China. The reduced root-mean-square errors for 1-, 2-, 3-, and 4-day forecasts during January 2018 were 51.2, 27.0, 16.4, and 9.4 µg m-3, respectively, which are 3.2, 6.9, 8.6, and 10.4 times those by the CTM forecasts with assimilated ICs. More pronounced improvements are found for highly reactive PM2.5 components. These and similar results for July 2017 suggest that our method can enhance and extend the impacts of the assimilated data without being affected by the imbalance issue.

Comparison of transoral endoscopic thyroidectomy vestibular approach, total endoscopic thyroidectomy via areola approach, and conventional open thyroidectomy: a retrospective analysis of safety, trauma, and feasibility of central neck dissection in the treatment of papillary thyroid carcinoma.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) and total endoscopic thyroidectomy via areola approach (ETA) are commonly used endoscopic thyroidectomy approaches. This study compares the effectiveness of these approaches with conventional open thyroidectomy (COT) in terms of safety, associated trauma, and feasibility of central neck dissection in the treatment of papillary thyroid carcinoma (PTC). METHODS: This retrospective study included patients who underwent TOETVA (n = 100), ETA (n = 119), and COT (n = 289). All patients had a pathological diagnosis of PTC and underwent unilateral lobectomy and central neck dissection. We analyzed operative time, postoperative drainage volume, postoperative C-reactive protein (CRP), preoperative and postoperative white blood cell (WBC) count and parathyroid hormone (PTH) levels, parathyroid damage, hoarseness, total number of central lymph nodes, and number of metastatic central lymph nodes. RESULTS: The clinical characteristics across the three groups were similar except for patient sex and age. There was a higher proportion of young women in the TOETVA and ETA groups than in the COT group. There were significant differences between the three groups regarding operative time (P = 0.000), postoperative drainage volume (P = 0.000), postoperative CRP (P = 0.000), ∆WBC (P = 0.000), and length of postoperative hospital stay (P = 0.021); in the TOETVA and ETA groups, operative time (P = 0.445), postoperative drainage volume (P = 0.677), and length of postoperative hospital stay (P = 0.145) were not significantly different. The percentage of cases with parathyroid gland damage (P = 0.459) and hoarseness (P > 0.05) was similar in all groups. All three procedures were efficient in performing a central lymph node dissection. CONCLUSIONS: Although considered more traumatic, TOETVA and ETA are both safe treatment options for PTC. They can both achieve similar therapeutic effects of central neck dissection in the treatment of PTC when compared with open surgery.

Enhancing ontology-driven diagnostic reasoning with a symptom-dependency-aware Naïve Bayes classifier.

BACKGROUND: Ontology has attracted substantial attention from both academia and industry. Handling uncertainty reasoning is important in researching ontology. For example, when a patient is suffering from cirrhosis, the appearance of abdominal vein varices is four times more likely than the presence of bitter taste. Such medical knowledge is crucial for decision-making in various medical applications but is missing from existing medical ontologies. In this paper, we aim to discover medical knowledge probabilities from electronic medical record (EMR) texts to enrich ontologies. First, we build an ontology by identifying meaningful entity mentions from EMRs. Then, we propose a symptom-dependency-aware naïve Bayes classifier (SDNB) that is based on the assumption that there is a level of dependency among symptoms. To ensure the accuracy of the diagnostic classification, we incorporate the probability of a disease into the ontology via innovative approaches. RESULTS: We conduct a series of experiments to evaluate whether the proposed method can discover meaningful and accurate probabilities for medical knowledge. Based on over 30,000 deidentified medical records, we explore 336 abdominal diseases and 81 related symptoms. Among these 336 gastrointestinal diseases, the probabilities of 31 diseases are obtained via our method. These 31 probabilities of diseases and 189 conditional probabilities between diseases and the symptoms are added into the generated ontology. CONCLUSION: In this paper, we propose a medical knowledge probability discovery method that is based on the analysis and extraction of EMR text data for enriching a medical ontology with probability information. The experimental results demonstrate that the proposed method can effectively identify accurate medical knowledge probability information from EMR data. In addition, the proposed method can efficiently and accurately calculate the probability of a patient suffering from a specified disease, thereby demonstrating the advantage of combining an ontology and a symptom-dependency-aware naïve Bayes classifier.

Detecting multiple variants associated with disease based on sequencing data of case-parent trios.

With the advance of next-generation sequencing technology, the rare variants join the common ones in explaining more proportions of heritability. The coexistence of variants of common with rare, causal with neutral and deleterious with protective is a norm and should be appropriately addressed. Some existing methods suffer from low power when one or more forms of coexistence present, impeding their applications in practice. In this paper, for case-parent trios, pseudocontrols are constructed using the nontransmitted alleles of the parents. The Kullback-Leibler divergence is utilized to measure the difference between the distributions of variants in a genetic region for the affected children and pseudocontrols, and two nonparametric test statistics KLTT and cKLTT are proposed. Extensive simulations show that they are robust to the opposite directions of the causal variants and the amount of neutral variants, and have superiority over the existing methods when both rare and common variants are involved. Furthermore, their efficiency is demonstrated in the application to the data from Framingham Heart Study.

Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression.

BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

Pin1 is related with clinical stage of papillary thyroid carcinoma.

BACKGROUND: The context and aim of this article was to investigate whether the expression level of Pin1 was in association with the clinical stage of papillary thyroid carcinomas. METHODS: Seventy-two patients who had been treated at the Affiliated Hospital of Qingdao University - Yantai YuHuangDing Hospital during January 2013 to December 2014 were rolled in. The expression levels of Pin1 using immunohistochemistry were tested and were divided into four groups according to the different clinical stages and final scores based on multiplying intensity and percentage value of IHC results. Data was analyzed with SPSS 20.0, and P value <0.05 had been chosen as significant. RESULTS: Considered from analysis result, the Pin1 expression status statistically significantly correlated with the PTC clinical stages (χ(2) = 8.128, P = 0.043); as the clinical stage proceeded, the intensity of Pin1 in PTC cells had been increased. But we did not find any relationships between immunohistochemical staining results and other clinicopathological characteristics. CONCLUSIONS: The PTC cells' intensity of Pin1 was in association with the clinical stage. The role played by Pin1 in PTC has been studied, and we need to further investigate the application of Pin1 in the treatment of PTC.

The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats.

The objective of this work was to investigate the effect of orally administered silibinin on the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 1.0 mg/kg ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine and N-desmethylivabradine were estimated by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated using the DAS 2.0 software. The pharmacokinetic parameters of t1/2, Cmax, AUC(0-t) and AUC(0-∞) of ivabradine in the combination group were significantly higher than those in the control group (p < 0.01). However, silibinin has no effect on the pharmacokinetics of N-desmethylivabradine. This study demonstrates that silibinin increase plasma concentration of ivabradine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing ivabradine to patients already taking silibinin.