REACTIN: Regulatory Activity Inference of Transcription Factors Underlying Human Diseases with Application to Breast Cancer

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients

Research Issues, Challenges, and Opportunities of Wireless Power Transfer-Aided Full-Duplex Relay Systems

We present a comprehensive review for wireless power transfer (WPT)-aided full-duplex (FD) relay systems. Two critical challenges in implementing WPT-aided FD relay systems are presented, that is, pseudo FD realization and high power consumption. Existing time-splitting or power-splitting structure based-WPT-aided FD relay systems can only realize FD operation in one of the time slots or only forward part of the received signal to the destination, belonging to pseudo FD realization. Besides, self-interference is treated as noise and self-interference cancellation (SIC) operation incurs high power consumption at the FD relay node. To this end, a promising solution is outlined to address the two challenges, which realizes consecutive FD realization at all times and forwards all the desired signal to the destination for decoding. Also, active SIC, that is, analog/digital cancellation, is not required by the proposed solution, which effectively reduces the circuit complexity and releases high power consumption at the FD relay node. Specific classifications and performance metrics of WPT-aided FD relay systems are summarized. Some future research is also envisaged for WPT-aided FD systems

Rodent hole detection in a typical steppe ecosystem using UAS and deep learning

IntroductionRodent outbreak is the main biological disaster in grassland ecosystems. Traditional rodent damage monitoring approaches mainly depend on costly field surveys, e.g., rodent trapping or hole counting. Integrating an unmanned aircraft system (UAS) image acquisition platform and deep learning (DL) provides a great opportunity to realize efficient large-scale rodent damage monitoring and early-stage diagnosis. As the major rodent species in Inner Mongolia, Brandt’s voles (BV) (Lasiopodomys brandtii) have markedly small holes, which are difficult to identify regarding various seasonal noises in this typical steppe ecosystem.MethodsIn this study, we proposed a novel UAS-DL-based framework for BV hole detection in two representative seasons. We also established the first bi-seasonal UAS image datasets for rodent hole detection. Three two-stage (Faster R-CNN, R-FCN, and Cascade R-CNN) and three one-stage (SSD, RetinaNet, and YOLOv4) object detection DL models were investigated from three perspectives: accuracy, running speed, and generalizability.ResultsExperimental results revealed that: 1) Faster R-CNN and YOLOv4 are the most accurate models; 2) SSD and YOLOv4 are the fastest; 3) Faster R-CNN and YOLOv4 have the most consistent performance across two different seasons.DiscussionThe integration of UAS and DL techniques was demonstrated to utilize automatic, accurate, and efficient BV hole detection in a typical steppe ecosystem. The proposed method has a great potential for large-scale multi-seasonal rodent damage monitoring

Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions

Background/Aims Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCA-mediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis

Danhong Injection Reversed Cardiac Abnormality in Brain–Heart Syndrome via Local and Remote β-Adrenergic Receptor Signaling

Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain–heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain–heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms. We investigated the role of DHI in the setting of brain–heart syndrome and determined the mechanism by which it regulates this process. We induced Ischemia/Reperfusion in Wistar rats and administered intravenous dose of DHI twice daily for 14 days. We assessed the neurological state, infarct volume, CT scan, arterial blood pressure, heart rhythm, and the hemodynamics. We harvested the brain and heart tissues for immunohistochemistry and western blot analyses. Our data show that DHI exerts potent anti-stroke effects (infarct volume reduction: ∗∗p < 0.01 and ∗∗∗p < 0.001 vs. vehicle. Neurological deficit correction: ∗p < 0.05 and ∗∗∗p < 0.001 vs. vehicle), and effectively reversed the abnormal arterial pressure (∗p < 0.05 vs. vehicle) and heart rhythm (∗∗p < 0.01 vs. vehicle). The phenotype of this brain–heart syndrome is strikingly similar to those of MI model. Quantitative assessment of hemodynamic in cardiac functionality revealed a positive uniformity in the PV-loop after administration with DHI and valsartan in the latter. Immunohistochemistry and western blot results showed the inhibitory effect of DHI on the β-adrenergic pathway as well as protein kinase C epsilon (PKCε) (∗∗p < 0.01 vs. model). Our data showed the underlying mechanisms of the brain–heart interaction and offer the first evidence that DHI targets the adrenergic pathway to modulate cardiac function in the setting of brain–heart syndrome. This study has made a novel discovery for proper application of the multi-target DHI and could serve as a therapeutic option in the setting of brain–heart syndrome

Well-dispersed Pd–Sn nanocatalyst anchored on TiO 2 nanosheets with enhanced activity and durability for ethanol electarooxidation

Abstract(#br)Novel Pd 1 -Sn x /TiO 2 nanosheets catalyst with higher activity and durability for ethanol oxidation (EOR) was obtained by NaBH 4 co-reduction method in direct ethanol fuel cells (DEFCs). The electrochemical performance tested under alkaline conditions illustrates that the prepared Pd 1 –Sn 0.6 /TiO 2 NSs catalyst presents outstanding activity (3381 mA mg Pd − 1 ) and excellent CO anti-poisoning ability for EOR. Meanwhile, the residual current density of Pd 1 –Sn 0.6 /TiO 2 NSs nanocatalyst (1207 mA mg Pd − 1 ) is 8.5 times of the Pd/C (JM) catalyst (142 mA mg Pd − 1 ) after the durability test of 5000 s for EOR. Additionally, the Pd 1 -Sn x /TiO 2 nanosheets show prominent electrocatalytic activity in EOR comparison with Pd/TiO 2 nanosheets and Pd–Sn nanocatalysts. Thus, Pd and Sn doped in TiO 2 nanosheets not only display excellent electrocatalytic, but also reduce the cost of Pd, which have some reference value for DEFCs

Ион-парная ВЭЖХ производных пиримидина и пурина

ПИРИМИДИНЫГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ ОДНОКОЛЬЦЕВЫЕПУРИНЫГЕТЕРОЦИКЛИЧЕСКИЕ СОЕДИНЕНИЯ ДВУХКОЛЬЦЕВЫЕХРОМАТОГРАФИЯ ЖИДКОСТНАЯ ВЫСОКОГО ДАВЛЕНИЯХРОМАТОГРАФИЯ ИОНООБМЕННАЯДНКРНКПРОТИВООПУХОЛЕВЫЕ СРЕДСТВАПРОТИВОВИРУСНЫЕ СРЕДСТВ

Musca domestica Cecropin (Mdc) Alleviates Salmonella typhimurium-Induced Colonic Mucosal Barrier Impairment: Associating With Inflammatory and Oxidative Stress Response, Tight Junction as Well as Intestinal Flora

Salmonella typhimurium, a Gram-negative food-borne pathogen, induces impairment in intestinal mucosal barrier function frequently. The injury is related to many factors such as inflammation, oxidative stress, tight junctions and flora changes in the host intestine. Musca domestica cecropin (Mdc), a novel antimicrobial peptide containing 40 amino acids, has potential antibacterial, anti-inflammatory, and immunological functions. It remains unclear exactly whether and how Mdc reduces colonic mucosal barrier damage caused by S. typhimurium. Twenty four 6-week-old male mice were divided into four groups: normal group, control group (S. typhimurium-challenged), Mdc group, and ceftriaxone sodium group (Cs group). HE staining and transmission electron microscopy (TEM) were performed to observe the morphology of the colon tissues. Bacterial load of S. typhimurium in colon, liver and spleen were determined by bacterial plate counting. Inflammatory factors were detected by enzyme linked immunosorbent assay (ELISA). Oxidative stress levels in the colon tissues were also analyzed. Immunofluorescence analysis, RT-PCR, and Western blot were carried out to examine the levels of tight junction and inflammatory proteins. The intestinal microbiota composition was assessed via 16s rDNA sequencing. We successfully built and evaluated an S. typhimurium-infection model in mice. Morphology and microcosmic change of the colon tissues confirmed the protective qualities of Mdc. Mdc could inhibit colonic inflammation and oxidative stress. Tight junctions were improved significantly after Mdc administration. Interestingly, Mdc ameliorated intestinal flora imbalance, which may be related to the improvement of tight junction. Our results shed a new light on protective effects and mechanism of the antimicrobial peptide Mdc on colonic mucosal barrier damage caused by S. typhimurium infection. Mdc is expected to be an important candidate for S. typhimurium infection treatment