Aortic isthmus flow reversal in fetal coarctation of the aorta and the associated factors.

INTRODUCTION: The aim of this study was to investigate the presence of aortic isthmus flow reversal and its associated factors in fetuses with positive and false-positive coarctation of the aorta (CoA) compared with normal controls. MATERIAL AND METHODS: Pregnant women with fetuses suspected of CoA and normal control were enrolled, and these women experienced prenatal ultrasound scan and followed up for 6 months after birth to confirm the presence of CoA. All the ultrasound parameters were analyzed. RESULTS: A total of 134 pregnant women were enrolled, with 43 CoA-positive fetuses and 91 CoA false-positive fetuses, and 334 matched pregnant women were enrolled in the control group. Aortic isthmus flow reversal occurred in 28 (65.1%) fetuses in the CoA-positive group, significantly (p < 0.05) more than in the false-positive (37 or 40.7%) or control group (64 or 19.2%). Aortic isthmus flow reversal was mostly in the full systole (n = 17 or 60.7%) or late systole and early-middle diastole (n = 10 or 35.7%) in the CoA-positive fetuses (n = 27 or 96.4%), significantly (p < 0.001) different from that in the false-positive or control group. The aortic isthmus flow reversal peak systolic velocity (PSV), flow volume, and ratio of reversed flow/forward flow were significantly (p < 0.05) increased in the CoA-positive and false-positive groups than in the control group. The aortic isthmus flow reversal incidence was significantly (p < 0.05) correlated with the middle cerebral artery (MCA) PSV in the total three groups or in the false-positive group but was significantly (p < 0001) negatively correlated with the MCA resistance index (RI) in the CoA-positive group. The incidence of the aortic isthmus flow reversal was significantly (p < 0.05) positively correlated with the umbilical artery (UA) RI in the false-positive group and with the UA RI in the total three groups. Independently associated factors for aortic isthmus flow reversal were isthmic flow volume/CCO (combined cardiac output) in the CoA-positive group. CONCLUSIONS: Reversal of flow in the aortic isthmus is much more common in true-positive cases of CoA as compared to controls, and isthmic flow reversal in the full systolic phase only suggests presence of CoA. The aortic isthmic reversed flow volume accounts for over half of the isthmic forward flow volume in the CoA-positive fetuses than in the normal controls.

Ultrasound parameters of arteries and heart in normal fetuses.

BACKGROUND: Currently, no normal ultrasound data of the fetuses during the 20-40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20-40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. METHODS: Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. RESULTS: 417 normal fetuses were enrolled. A significant (P < 0.05) negative correlation with the gestational age was detected in the peak systolic velocity/peak diastolic velocity (S/D), pulsatility index (PI) and resistance index (RI) of the umbilical artery (UA). A relatively stable relationship with the gestational age was detected in the fetal weight%, S/D, PI and RI of the middle cerebral artery (MCA), peak systolic velocity (PSV) and velocity time integral (VTI) of the intra-abdominal UA, fetal heart to chest ratio, mitral valve (MV)- and tricuspid valve (TV)-E/A peak flow velocity, aortic isthmic Z-score and displacement, distance between the brachiocephalic artery-left common carotid artery (BA-LCCA) and LCCA-left subclavian artery (LSA), Z-score of aorta, ascending aorta (AAO), pulmonary artery (PA), main pulmonary artery (MPA), and descending aorta (DAO). A significant (P < 0.05) positive correlation with the gestational age was detected in the fetal biological data, MCA PSV and VTI, free-UA PSV and VTI and cardio-thoracic ratio, cardiac parameters, ductus arteriosus (DA) and isthmus diameter, aortic parameters, PA and MPA diameter, MPA PSV and VTI, isthmus flow volume and velocity and PA flow volume, DA and BA parameters, and LCCA and LSA parameters (flow volume, PSV, and VTI). CONCLUSION: A certain correlation and distribution trend is detected in the ultrasound parameters of normal fetuses, and the ratios among different parameters remain relative stable. These findings can be used for determination of abnormal growth of the fetuses in prenatal ultrasound scan.

Screening of four lysosome-related genes in sepsis based on RNA sequencing technology.

PURPOSE: Screening of lysosome-related genes in sepsis patients to provide direction for lysosome-targeted therapy. METHODS: Peripheral blood samples were obtained from 22 patients diagnosed with sepsis and 10 normal controls for the purpose of RNA sequencing and subsequent analysis of differential gene expression. Concurrently, lysosome-related genes were acquired from the Gene Ontology database. The intersecting genes between the differential genes and lysosome-related genes were then subjected to PPI, GO and KEGG analyses. Core genes were identified through survival analysis, and their expression trends in different groups were determined using meta-analysis. Single-cell RNA sequencing was used to clarify the cellular localization of core genes. RESULTS: The intersection of 1328 sepsis-differential genes with 878 lysosome-related genes yielded 76 genes. PPI analysis showed that intersecting genes were mainly involved in Cellular process, Response to stimulus, Immune system process, Signal transduction, Lysosome. GO and KEGG analysis showed that intersecting genes were mainly involved in leukocyte mediated immunity, cell activation involved in immune response, lytic vacuole, lysosome. Survival analysis screened four genes positively correlated with sepsis prognosis, namely GNLY, GZMB, PRF1 and RASGRP1. The meta-analysis revealed that the expression levels of these four genes were significantly higher in the normal control group compared to the sepsis group, which aligns with the findings from RNA sequencing data. Furthermore, single-cell RNA sequencing demonstrated that T cells and NK cells exhibited high expression levels of GNLY, GZMB, PRF1, and RASGRP1. CONCLUSION: GNLY, GZMB, PRF1, and RASGRP1, which are lysosome-related genes, are closely linked to the prognosis of sepsis and could potentially serve as novel research targets for sepsis, offering valuable insights for the development of lysosome-targeted therapy. The clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019.

Comparative Analysis of Doppler Ultrasound Combined with Serum PAPP-A in Diagnosis and Pathology of Placenta Accreta.

Objective: To explore the value of Doppler ultrasound combined with the serum pregnancy associated plasma protein A (PAPP-A) in the diagnosis and pathology of placenta accreta. Methods: For the method of retrospective study, the data of 250 pregnant women with cesarean section delivery in our hospital from February 2020 to February 2021 were analyzed, and the prenatal examination of pregnant women was performed by Doppler ultrasound and the serum PAPP-A level was determined by serology detection. They were divided into the placenta accreta group (n=152) and non-placenta accreta group (n=98) according to the pathological results after delivery to compare the imaging data and the serum PAPP-A levels in the two groups. The receiver operating characteristic curve (ROC curve) was drawn with the pathological results as the gold standard. Results: The serum PAPP-A level in the placenta accreta group was overtly lower than that in the non-placenta accreta group (698.65±9.65 vs 910.57±9.65, t = 169.52, P < .001). In the placenta accreta group, there were 126 cases (82.89%) with irregular gyrate liquid dark area formed in the placenta of pregnant women, 78 cases (51.32%) with partial or all disappearance of posterior placenta space, 22 cases (14.74%) with the attenuation or disappearance of myometrium in the placental attachment, and 20 cases (13.16%) with abnormal placental thickening. The sensitivity, specificity, positive predictive value and negative predictive value of the Doppler ultrasound combined with serum diagnosis of PAPP-A were 86.84%, 79.59%, 86.84% and 79.59%, respectively. ROC analysis showed that the area under the curve (AUC) of Doppler ultrasound combined with serum diagnosis of PAPP-A was 0.835, with the asymptotic Sig.b < .001 and an asymptotic 95% confidence interval (CI) of 0.780-0.891. Conclusion: Doppler ultrasound could analyze the pathological manifestations of placenta accreta, and serum PAPP-A could be combined to improve the detection rate of placenta accreta, with a certain clinical application value.

Light and Potassium Improve the Quality of Dendrobium officinale through Optimizing Transcriptomic and Metabolomic Alteration.

BACKGROUND: Dendrobium officinale is a perennial epiphytic herb in Orchidaceae. Cultivated products are the main alternative for clinical application due to the shortage of wild resources. However, the phenotype and quality of D. officinale have changed post-artificial cultivation, and environmental cues such as light, temperature, water, and nutrition supply are the major influencing factors. This study aims to unveil the mechanisms beneath the cultivation-induced variation by analyzing the changes of the metabolome and transcriptome of D. officinale seedlings treated with red- blue LED light and potassium fertilizer. RESULTS: After light- and K-treatment, the D. officinale pseudobulbs turned purple and the anthocyanin content increased significantly. Through wide-target metabolome analysis, compared with pseudobulbs in the control group (P), the proportion of flavonoids in differentially-accumulated metabolites (DAMs) was 22.4% and 33.5% post light- and K-treatment, respectively. The gene modules coupled to flavonoids were obtained through the coexpression analysis of the light- and K-treated D. officinale transcriptome by WGCNA. The KEGG enrichment results of the key modules showed that the DEGs of the D. officinale pseudobulb were enriched in phenylpropane biosynthesis, flavonoid biosynthesis, and jasmonic acid (JA) synthesis post-light- and K-treatment. In addition, anthocyanin accumulation was the main contribution to the purple color of pseudobulbs, and the plant hormone JA induced the accumulation of anthocyanins in D. officinale. CONCLUSIONS: These results suggested that light and potassium affected the accumulation of active compounds in D. officinale, and the gene-flavone network analysis emphasizes the key functional genes and regulatory factors for quality improvement in the cultivation of this medicinal plant.

Direct Electrochemical Selenylation/Cyclization of Alkenes: Access to Functionalized Benzheterocycles.

A catalyst-free, environmentally friendly, and efficient electrochemical selenylation/cyclization of alkenes has been developed with moderate to excellent yields. This selenylated transformation proceeds smoothly and tolerates a wide range of synthetically useful groups to deliver diverse functionalized benzheterocycles, including iminoisobenzofuran, lactones, oxindoles, and quinolinones. Moreover, the present synthetic route could also be readily scaled up to gram quantity with convenient operation in an undivided cell.

A construction waste landfill dataset of two districts in Beijing, China from high resolution satellite images.

Construction waste is unavoidable in the process of urban development, causing serious environmental pollution. Accurate assessment of municipal construction waste generation requires building construction waste identification models using deep learning technology. However, this process requires high-quality public datasets for model training and validation. This study utilizes Google Earth and GF-2 images as the data source to construct a specific dataset of construction waste landfills in the Changping and Daxing districts of Beijing, China. This dataset contains 3,653 samples of the original image areas and provides mask-labeled images in the semantic segmentation domains. Each pixel within a construction waste landfill is classified into 4 categories of the image areas, including background area, vacant landfillable area, engineering facility area, and waste dumping area. The dataset contains 237,115,531 pixels of construction waste and 49,724,513 pixels of engineering facilities. The pixel-level semantic segmentation labels are provided to quantify the construction waste yield, which can serve as the basic data for construction waste extraction and yield estimation both for academic and industrial research.

Exploring Information Exchange between Thesium chinense and Its Host Prunella vulgaris through Joint Transcriptomic and Metabolomic Analysis.

BACKGROUND: Thesium chinense known as the "plant antibiotic" is a facultative root hemi-parasitic herb while Prunella vulgaris can serve as its host. However, the molecular mechanisms underlying the communication between T. chinense and its host remained largely unexplored. The aim of this study was to provide a comprehensive view of transferred metabolites and mobile mRNAs exchanged between T. chinense and P. vulgaris. RESULTS: The wide-target metabolomic and transcriptomic analysis identified 5 transferred metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside, pruvuloside B, 2-ethylpyrazine) and 50 mobile genes between T. chinense and P. vulgaris, as well as haustoria formation related 56 metabolites and 44 genes. There were 4 metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside and pruvuloside B) that are transferred from P. vulgaris to T. chinense, whereas 2-ethylpyrazine was transferred in the opposite direction. Furthermore, we inferred a regulatory network potentially involved in haustoria formation, where three metabolites (N,N'-Dimethylarginine/SDMA, NG,NG-Dimethyl-L-arginine, 2-Acetoxymethyl-anthraquinone) showed significant positive correlations with the majority of haustoria formation-related genes. CONCLUSIONS: These results suggested that there was an extensive exchange of information with P. vulgaris including transferred metabolites and mobile mRNAs, which might facilitate the haustoria formation and parasition of T. chinense.

A deep reinforcement learning-based wireless body area network offloading optimization strategy for healthcare services.

Wireless body area network (WBAN) is widely adopted in healthcare services, providing remote real-time and continuous healthcare monitoring. With the massive increase of detective sensor data, WBAN is largely restricted by limited storage and computation capacity, resulting in severely decreased efficiency and reliability. Mobile edge computing (MEC) technique can be combined with WBAN to resolve this issue. This paper studies the joint optimization problem of computational offloading and resource allocation (JCORA) in MEC for healthcare service scenarios. We formulate JCORA as a Markov decision process and propose a deep deterministic policy gradient-based WBAN offloading strategy (DDPG-WOS) to optimize time delay and energy consumption in interfered transmission channels. This scheme employs MEC to mitigate the computation pressure on a single WBAN and increase the transmission ability. Further, DDPG-WOS optimizes the offloading strategy-making process by considering the channel condition, transmission quality, computation ability and energy consumption. Simulation results verify the effectiveness of the proposed optimization schema in reducing energy consumption and computation latency and increasing the utility of WBAN compared to two competitive solutions.

Cardiac structural and functional remodeling in the fetuses associated with maternal hypothyroidism during pregnancy.

OBJECTIVES: We sought to investigate the effect of maternal hypothyroidism during pregnancy on fetal cardiac structural and functional remodeling using fetal echocardiography. METHODS: A total of 59 pregnant women with history of hypothyroidism were prospectively enrolled as the study group, and 74 normal fetuses as the control group. Fetal echocardiography was performed on each subject. Demographic, clinical, and fetal echocardiographic variables were measured, including left ventricular (LV) and right ventricular (RV) free wall and ventricular septal thickness, fractional shortening (FS), stroke volume (SV), cardiac output (CO), combined cardiac output (CCO), cardiac index (CI), combined cardiac index (CCI), aortic and pulmonary artery velocity, ductus venosus (DV) and pulmonary vein (PV) spectral Doppler, and Tei index. RESULTS: The incidence of echogenic intracardiac foci (EIF) was higher in the study group than that in the control group (18.6% vs. 6.8%, p = .036). The thickness of LV free wall and interventricular septum was reduced, the pulmonary velocities and CCI, RV FS, CO, and CI were lower, the S, D, S/A, and pulsatility index (PI) of DV were higher, and LV Tei index was higher in the study group compared with the control group. There was no significant difference in other variables between the two groups. CONCLUSIONS: There is cardiac remodeling, and systolic, diastolic functional alterations in fetuses with maternal hypothyroidism. Further investigation is warranted to develop strategies to optimize the outcome of these fetuses.

Construction of a Two-Gene Immunogenomic-Related Prognostic Signature in Lung Squamous Cell Carcinoma.

Lung cancer has the highest tumor incidence in China. Lung squamous cell carcinoma (LUSC) is the most common type, accounting for 40-51% of primary lung cancers. LUSC is slow in growth and late in metastasis. Immune-related genes (IRGs) and immune infiltrating cells play a vital role in the clinical outcomes of LUSC. It is important to systematically study its immune gene map to help the prognosis of cancer patients. In this study, we combined the prognostic landscape and expression status of IRGs downloaded from the TCGA and InnatedDB databases and systematically analyzed the prognostic information of LUSC patients to obtain IRGs. After systematically exploring the survival analysis, prognosis-related genes were found, and the PPI network revealed that a total of 11 genes were hub genes. A two-gene prognosis risk model was established by multivariate Cox analysis. Two IRGs were closely correlated with the prognosis of LUSC. Based on these two genes, a new independent prognostic risk model was established, and this model was further verified in the GEO database. Moreover, the risk score of the model was correlated with sex, survival status, and lymphatic metastasis in LUSC patients, and the predictive risk of the prognostic risk model was significantly positively correlated with five kinds of immune cells (CD4 T cells, CD8 T cells, neutrophils, macrophages, and dendritic cells). This study comprehensively analyzed immunogenomics and presented immune-related prognostic biomarkers for LUSC.

Evaluation of the Prognostic Value of Long Noncoding RNAs in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) is the most common type of lung cancer accounting for 40% to 51%. Long noncoding RNAs (lncRNAs) have been reported to play a significant role in the invasion, migration, and proliferation of lung cancer tissue cells. However, systematic identification of lncRNA signatures and evaluation of the prognostic value for LUSC are still an urgent problem. In this work, LUSC RNA-seq data were collected from TCGA database, and the limma R package was used to screen differentially expressed lncRNAs (DElncRNAs). In total, 216 DElncRNAs were identified between the LUSC and normal samples. lncRNAs associated with prognosis were calculated using univariate Cox regression analysis. The overall survival (OS) prognostic model containing 10 lncRNAs and the disease-free survival (DFS) prognostic model consisting of 11 lncRNAs were constructed using a machine learning-based algorithm, systematic LASSO-Cox regression analysis. We found that the survival rate of samples in the high-risk group was lower than that in the low-risk group. Results of ROC curves showed that both the OS and DFS risk score had better prognostic effects than the clinical characteristics, including age, stage, gender, and TNM. Two lncRNAs (LINC00519 and FAM83A-AS1) that were commonly identified as prognostic factors in both models could be further investigated for their clinical significance and therapeutic value. In conclusion, we constructed lncRNA prognostic models with considerable prognostic effect for both OS and DFS of LUSC.

Circular RNA TAF4B Promotes Bladder Cancer Progression by Sponging miR-1298-5p and Regulating TGFA Expression.

BACKGROUND: Bladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown. METHODS: We detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa. RESULTS: In this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells in vivo. CONCLUSION: In summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.

Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

LHPP Inhibits the Proliferation and Metastasis of Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the ten most common cancers in the globe. Despite the diagnosis and treatment of renal cell carcinoma that have made great improvements, the morbidity and mortality rates of renal cell carcinoma remain unchanged remarkably. LHPP is a kind of histidine phosphatases, acting as a tumor suppressor in the progression of various cancers. In this study, we found that LHPP was significantly downregulated in RCC tissues and cell lines. Decreased expression of LHPP was closely correlated with tumor size and postoperative metastasis of RCC patients. In addition, overexpression of LHPP inhibited the proliferation and metastasis of RCC. However, suppression of LHPP promoted the proliferation and metastasis of RCC. In conclusion, our results presented the important role of LHPP in the development and progression of RCC.

Effects of sacubitril/valsartan in patients with heart failure and chronic kidney disease: A meta-analysis.

Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients with heart failure and chronic kidney disease (CKD) with the inhibitor of renal angiotensin system (RAS) are limited. To further demonstrate the benefits of sacubitril/valsartan in patients with both heart failure and CKD, a meta-analysis of randomized controlled trials (RCTs) was conducted. The Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov were searched for RCTs. A total of 3460 individuals with heart failure and CKD were included in this meta-analysis. Sacubitril/valsartan was compared with irbesartan, valsartan and enalapril. It was found that sacubitril/valsartan significantly increased estimated glomerular filtration rate [eGFR, MD = 1.90, 95% CI (0.30, 3.50), P = 0.02]. However, sacubitril/valsartan had no difference in urinary albumin/creatinine ratio [UACR, MD = -0.30, 95% CI (-1.38, 0.78), P = 0.59] compared to the control group. Sacubitril/valsartan showed dramatically decrease in systolic blood pressure [SBP, MD = -4.39, 95% CI (-6.11, -2.68), P < 0.001], diastolic blood pressure [DBP, MD = -2.69, 95% CI (-4.04, -1.35), P < 0.001], and N-terminal prohormone brain natriuretic peptide [NT-proBNP, MD = -45.34, 95% CI (-46.63, -44.06), P < 0.001]. There was no significant difference in the incidence of adverse reactions between sacubitril/valsartan and the control group. Compared with the RAS inhibitor, sacubitril/valsartan significantly increased eGFR and decreased BP and NT-proBNP, which indicates that it might have cardiovascular and renal benefits in patients with heart failure and CKD.

Nuclear-targeted p53 and DOX co-delivery of chitosan derivatives for cancer therapy in vitro and in vivo.

The nucleus is one of the most important cellular organelles. Chitosan-grafted poly-(N-3-carbobenzyloxy-lysine) (CCL) decorated with human immunodeficiency virus-1 transactivator of transcription (TAT) can co-deliver p53 and doxorubicin into the nucleus simultaneously, such that their antitumor functions are exerted. However, TAT-CCL has been shown to have an anti-tumor effect only in vitro; the effect in vivo was unsatisfactory. Here, a unique nucleus-targeted delivery system based on amidized TAT (aTAT)-CCL with aTAT functional on the surface was designed to achieve a highly efficient nucleus-targeting gene and drug delivery system for effective cancer cell elimination in vitro and in vivo. In this delivery system, TAT is amidized to inhibit its nonspecific interactions. Confocal laser scanning microscopy observations revealed that if aTAT-CCL was incubated in pH 5.0 acetate buffer solution for 24 h before use (named aTAT-CCL-HB), more aTAT-CCL-HB entered the nucleus compared with aTAT-CCL or CCL. aTAT-CCL-HB can also achieve high gene transfection and drug delivery efficiencies and low viability in HepG2 cells. However, only aTAT-CCL achieved extensive circulation in the blood compartment and high antitumor activity in vivo. Amidization of TAT in vectors may become a promising strategy for nucleus-targeted delivery systems, especially in in vivo applications.

Downregulated miR-21 mediates matrine-induced apoptosis via the PTEN/Akt signaling pathway in FTC-133 human follicular thyroid cancer cells.

Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC-133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC-133 cells in a dose- and time-dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC-133 cells. The expression level of microRNA (miR)-21 was analyzed by reverse transcription-quantitative PCR (RT-qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)-Akt were detected by RT-qPCR analysis and western blotting, respectively. The expression of miR-21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p-Akt was downregulated in the FTC-133 cells. The effects of miR-21 mimics and miR-21 inhibitor on the expression of miR-21, PTEN and Akt in FTC-133 cells, and the effect of miR-21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC-133 cells via the miR-21/PTEN/Akt signaling pathway.

Complete mitochondrial genome of a kind of snakehead fish Channa siamensis and its phylogenetic consideration.

The snakehead fish, Channa siamensis, belongs to the genus of Channa (perciformes: Channidae) and was first reported by Günther in 1861. Despite it has been described approximately for 15 decades, the genetic information is limited and the taxon status of this kind of fish is still unclear. The primary objective of this study is to get more genomic data and calculate the taxon location of this kind of fish. The next generation sequencing method was used to obtain the whole mitochondrial DNA information, and bioinformatic analysis was performed to investigate the evolutionary status and taxon location of C. siamensis. The circular mitochondrial DNA was 16,570 bp in length, and which showed typical piscine structure and arrangement. The overall nucleotide composition was 29.28% A, 24.72% T, 30.71% C, 15.29% G, with 54.1% AT, respectively. Phylogenetic analyses using concatenated amino acid and nucleotide sequences of the 13 protein-coding genes with two different methods (Maximum likelihood and Bayesian analysis) both highly supported C. siamensis belongs to the genus Channa and shows a close relationship with C. micropeltes. These data will provide more useful information for a better understanding of the mitochondrial genomic diversities and evolution in fish as well as novel genetic markers for studying population genetics and species identification.

A Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of Proposed Biosimilar GB242 and Reference Infliximab in Healthy Subjects.

OBJECTIVE: The objective of this study was to compare the pharmacokinetics (PKs), safety, and immunogenicity of GB242 as a potential biosimilar infliximab with those of reference infliximab in healthy Chinese subjects. METHODS: We conducted a randomized, single-center, double-blind, parallel-controlled phase I study in which 48 healthy subjects were divided equally into a GB242 group and reference infliximab group. Both the test and reference drug were administered as a single intravenous dose of 3 mg/kg. Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios of the GB242 to reference infliximab for maximum concentration (Cmax), area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUCt), and AUC from time zero to infinity (AUC∞) were within the predefined bioequivalence range of 80-125%. RESULTS: The mean serum concentration-time curves were similar between GB242 and reference infliximab. The 90% CIs for the geometric mean ratios of the GB242 to reference infliximab for Cmax, AUCt, and AUC∞ were completely within 80-125% for the PK similarity comparison. The proportion of subjects with treatment-emergent adverse events was similar between the GB242 group and the reference infliximab group. Antidrug antibody profiles were comparable between the two treatments groups. CONCLUSIONS: This study demonstrated high PK similarity between GB242 and its marketed reference infliximab in healthy subjects. Both treatments showed comparable safety and immunogenicity. REGISTRATION NUMBER: ChiCTR-IPR-15007098.