Drug interaction is a leading cause of adverse drug events and a major obstacle for current clinical practice. Pharmacovigilance data mining, pharmacokinetic modeling, and text mining are computation and informatic tools on integrating drug interaction knowledge and generating drug interaction hypothesis. We provide a comprehensive overview of these translational biomedical informatics methodologies with related databases. We hope this review illustrates the complementary nature of these informatic approaches and facilitates the translational drug interaction research.

Background: The negative effects of sedentary behavior (SB) on public health have been extensively documented. A large number of studies have demonstrated that high prevalence of SB is a critical factor of all-cause mortality. Globally, the frequency of SB research has continued to rise, but little is known about SB in the Chinese population. Therefore, this review was conducted to scope the research situation and to fill the gaps related to the effects of SB in the Chinese population. Methods: Using a scoping review based on York methodology, a comprehensive search of published journal articles and grey literature was carried out through 12 databases. The literature research was conducted by two authors in July 2019, and included journal articles that targeted on the Chinese population were published between 1999 and 2019. The two authors screened the records independently and included those research topics related to SB in the Chinese population. Results: The number of included studies increased from 1 to 29 per year during the analyzed period, during which, a remarkable climb happened from 8 in 2013 to 19 in July 2019. Out of the 1303 screened studies, a total of 162 studies (81 English and 81 Chinese journal articles) met the inclusion criteria in this review. Most of the included studies (66.0%) reported the overall estimated prevalence of SB, in which, 43.2% of studies reported the average time of SB, and 40.0% of studies reported the cutoff point of SB. Besides this, 54.9% and 23.5% of studies focused on the outcomes and correlates/determinants of SB, and the proportions of studies based on testing the validation of measurement tools and on interventions were 3.7% and 4.9%, respectively. Nearly all of the reviewed articles used data from cross-sectional studies (75.9%) and longitudinal studies (13.6%), while intervention trials are less developed. The majority of the studies (64.8%) used self-reported surveys, and only 3.7% studies used device-based measurement tools. Furthermore, 35.8% of the included studies were focused on children and adolescents, while only a few studies investigated infants/toddlers and older adults. Both female and male were examined in most studies, and non-clinical populations were investigated in the context of SB in a relatively large number of studies. Conclusions: The number of research articles on SB in the Chinese population published per year has increased year by year, indicating a growing interest in this research area. More studies using population subgroup samples are needed, particularly among infants/toddlers, older adults, and clinical populations. To provide stronger evidence of the determinants and outcomes of SB, longitudinal studies using device-based measures of SB are required.

Zinc-air batteries (ZABs) have several advantages, including high energy density, cheap price and stable performances with good application prospects in the field of power batteries. The charging and discharging reactions for the air cathode of ZABs are the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), respectively, which play an important role in the whole performance of ZAB. Due to the cost and limited reserves of highly active precious metal catalysts, it is crucial to design alternative efficient and stable dual-functional non-precious metal catalysts. In the present review, we present a systematic summary of the recent progress in the use of transition metal-based electrocatalysts as alternatives to precious metals for the positive poles of ZAB air. Combined with state-of-the-art in situ characterization technologies, a deep understanding of the catalytic mechanism of OER/ORR provided unique insights into the precise design of excellent synthetic non-precious metal catalysts from the perspective of atomic structure. This review further shows that the hybrid electric battery is a new strategy to improve the efficiency of the hybrid electric battery, which could be available to alleviate the problem of resource shortage. Finally, the challenges and research trends for the future development of ZABs were clearly proposed.

The application of an ultra-wideband (UWB) positioning system in a Global Positioning System (GPS) denial environment such as an underground coal mine, mainly focuses on position information and rarely involves information such as direction attitude. Position accuracy is often affected by multipath, non-visible ranges, base station layout, and more. We proposed an IMU-assisted UWB-based positioning system for the provision of positioning and orientation services to coal miners in underground mines. The Error-State Kalman Filter (ESKF) is used to filter the errors in the measured data from the IMU-assisted UWB positioning system to obtain the best estimate of the error for the current situation and correct for inaccuracies due to approximations. The base station layout of the IMU-assisted UWB positioning system was also simulated. The reasonable setting of the reference base station location can suppress multi-access interference and improve positioning accuracy to a certain extent. Numerous simulation experiments have been conducted in GPS denial environments, such as underground coal mines. The experimental results show the effectiveness of the method for determining the position, direction, and attitude of the coal miner under the mine, which provides a better reference value for positioning and orientation in a GPS rejection environment such as under the mine.

Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like the inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. This article aims to review the documents in this field and summarize the research hotspots as well as developing processes. Gut microbiota and immune microenvironment-related documents from 1976 to 2022 were obtained from the Web of Science Core Collection database. Bibliometrics was used to assess the core authors and journals, most contributive countries and affiliations together with hotspots in this field and keyword co-occurrence analysis. Data were visualized to help comprehension. Nine hundred and twelve documents about gut microbiota and immune microenvironment were retrieved, and the annual publications increased gradually. The most productive author, country, and affiliation were "Zitvogel L," USA and "UNIV TEXAS MD ANDERSON CANC CTR," respectively. FRONTIERS IN IMMUNOLOGY, CANCERS, and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE were the periodicals with most publications. Keyword co-occurrence analysis identified three clusters, including gut microbiota, inflammation, and IBD. Combined with the visualized analysis of documents and keyword co-occurrence as well as literature reading, we recognized three key topics of gut microbiota: cancer and therapy; immunity, inflammation and IBD; acute injuries and metabolic diseases. This article revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.IMPORTANCEGut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. While the application of bibliometrics in the field of gut microbiota and immune microenvironment still remains blank, which focused more on the regulation of the gut microbiota on the immune microenvironment of different kinds of diseases. Here, we intended to review and summarize the presented documents in gut microbiota and immune microenvironment field by bibliometrics. And we revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.

Diffusion-weighted magnetic resonance imaging (DWI) is a mature scanning technique. With high sensitivity in detecting cerebral infractions, it has become an essential part of the clinical evaluation of acute stroke. However, with the update in medical ideals and treatment, clinicians are now focusing on distinguishing between reversible and irreversible brain tissue damage rather than detecting ischaemic lesions alone.

In February 2020, an inpatient in Peking University People's Hospital (PKUPH), China, was confirmed positive for the novel coronavirus. In this case, 143 hemodialysis patients were labeled as close contacts and required to be placed under the hospital-based group medical quarantine (HB-GMQ) for 2 weeks by the authorities. After the case was reported, false or misleading information about the case flourished on social media platforms, which led to infodemic. Under this context, PKUPH adopted patient-centered humanistic care to implement the HB-GMQ, through the synergy of administrative, healthcare, logistical, and other measures under the model of patient-centered care of the Massachusetts Medical Society (MMS). As a result, all the patients tided over the HB-GMQ with no COVID-19 infection and no unanticipated adverse events, and all met the criteria for lifting the HB-GMQ. According to the questionnaires taken during the HB-GMQ, a high level of satisfaction was found among the quarantined and no symptomatic increase of anxiety and depression in the patients before and during the HB-GMQ, by comparing the Zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS) conducted in December 2019 and on the 12th day of the HB-GMQ. This article is to brief on PKUPH's experience in implementing patient-centered humanistic care tailored to hemodialysis patients under the HB-GMQ, and to validate the hypothesis that patient-centered humanistic care is effective and helpful to help them tide over the HB-GMQ, so as to shed light on how to implement the HB-GMQ and cope with the HB-GMQ-induced problems in other hospitals.

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8-week swimming model in wild-type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise-responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3XΔMφ), hepatocyte-specific DDX3X knockout (DDX3XΔhep), and wild-type control (DDX3Xfl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3Xfl/fl littermates, DDX3XΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3XΔhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3Xfl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Endophilin, which participates in membrane vesiculation during receptor-mediated endocytosis, is a ∼40 kDa SH3 domain-containing protein that binds to the proline/arginine-rich domain of dynamin, a ∼100 kDa GTPase that is essential for endocytic membrane scission. It has been suggested that endophilin is monomeric in the cytoplasm and dimerizes only after it binds to membranes (or perhaps to dimers or tetramers of dynamin). To clarify this issue, we studied the oligomeric state of endophilin both in vitro using analytical ultracentrifugation and fluorescence anisotropy, and in living cells using two-photon fluorescence fluctuation spectroscopy. We analyzed the fluctuation data using the Q-analysis method, which allowed us to determine the intrinsic brightness of the labeled protein complexes and hence its aggregation state in the cytoplasmic regions of the cell. Although a relatively high K(d) (∼5-15 μM) was observed in vitro, the cell measurements indicate that endophilin is dimeric in the cytoplasm, even at submicromolar concentrations. We also demonstrate that endophilin significantly enhances the assembly of dynamin, and that this enhancement is proportional to the fraction of dimeric endophilin that is present. Moreover, there is correlation between the concentrations of endophilin that promote dynamin self-assembly and those that stimulate dynamin GTPase activity. These findings support the view that endophilin-dynamin interactions play an important role in endocytosis.

Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation. PSAA photoisomerization at the GluN1 clamshell hinge is sufficient to control glycine sensitivity and activation efficacy. Strikingly, in the pore domain, flipping of a M3 residue within a conserved transmembrane cavity impacts both gating and permeation properties. Our study demonstrates the first detection of molecular rearrangements in real-time due to the reversible light-switching of single amino acid side-chains, adding a dynamic dimension to protein site-directed mutagenesis. This novel approach to interrogate neuronal protein function has general applicability in the fast expanding field of optopharmacology.

d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system. However, central mechanisms underlying these effects of d-allulose remain unknown. We recently reported that d-allulose activates the anorexigenic neurons in the hypothalamic arcuate nucleus (ARC), the neurons that respond to glucagon-like peptide-1 and that express proopiomelanocortin. However, its action on the orexigenic neurons remains unknown. This study investigated the effects of d-allulose on the ARC neurons implicated in hunger, by measuring cytosolic Ca2+ concentration ([Ca2+]i) in single neurons. d-allulose depressed the increases in [Ca2+]i induced by ghrelin and by low glucose in ARC neurons and inhibited spontaneous oscillatory [Ca2+]i increases in neuropeptide Y (NPY) neurons. d-allulose inhibited 10 of 35 (28%) ghrelin-responsive, 18 of 60 (30%) glucose-sensitive and 3 of 8 (37.5%) NPY neurons in ARC. Intracerebroventricular injection of d-allulose inhibited food intake at 20:00 and 22:00, the early dark phase when hunger is promoted. These results indicate that d-allulose suppresses hunger-associated feeding and inhibits hunger-promoting neurons in ARC. These central actions of d-allulose represent the potential of d-allulose to inhibit the hyperphagia with excessive appetite, thereby counteracting obesity and diabetes.

Within cells, the spatial compartmentalization of thousands of distinct proteins serves a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) can elucidate protein spatial relationships to global ultrastructure, but has suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional cryogenic SR and focused ion beam-milled block-face EM across entire vitreously frozen cells. The approach preserves ultrastructure while enabling independent SR and EM workflow optimization. We discovered unexpected protein-ultrastructure relationships in mammalian cells including intranuclear vesicles containing endoplasmic reticulum-associated proteins, web-like adhesions between cultured neurons, and chromatin domains subclassified on the basis of transcriptional activity. Our findings illustrate the value of a comprehensive multimodal view of ultrastructural variability across whole cells.

Glutathione peroxidase-1 (GPx1) is a pivotal intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. This study aims to identify a microRNA (miRNA) that targets GPx1 to maintain redox homeostasis. Dual luciferase assays combined with mutational analysis and immunoblotting were used to validate the bioinformatically predicted miRNAs. We sought to select miRNAs that were responsive to oxidative stress induced by hydrogen peroxide (H2O2) in the H9c2 rat cardiomyocyte cell line. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-181a in H2O2-treated H9c2 cells was markedly upregulated. The downregulation of miR-181a significantly inhibited H2O2-induced cellular apoptosis, ROS production, the increase in malondialdehyde (MDA) levels, the disruption of mitochondrial structure, and the activation of key signaling proteins in the mitochondrial apoptotic pathway. Our results suggest that miR-181a plays an important role in regulating the mitochondrial apoptotic pathway in cardiomyocytes challenged with oxidative stress. MiR-181a may represent a potential therapeutic target for the treatment of oxidative stress-associated cardiovascular diseases.

Background: The prognostic role of programmed cell death-ligand 1 (PD-L1) in bladder cancer has been investigated in previous studies, but the results remain inconclusive. Therefore, we carried out a meta-analysis to evaluate the prognostic significance of PD-L1 in patients with bladder cancer. Methods: The electronic databases PubMed, Embase, Web of Science, and Cochrane Library were searched. The association between PD-L1 expression and survival outcomes and clinicopathological factors was analyzed by hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 11 studies containing 1,697 patients were included in the meta-analysis. High PD-L1 expression was associated with poor overall survival (OS) (HR = 1.83, 95% CI = 1.24-2.71, p = 0.002). There was nonsignificant association between PD-L1 and recurrence-free survival (RFS) (HR = 1.43, 95% CI = 0.89-2.29, p = 0.134), cancer-specific survival (CSS) (HR = 1.51, 95% CI = 0.80-2.87, p = 0.203), or disease-free survival (DFS) (HR = 1.53, 95% CI = 0.88-2.65, p = 0.13). Furthermore, high PD-L1 was significantly correlated with higher tumor stage (OR = 3.9, 95% CI = 2.71-5.61, p < 0.001) and distant metastasis (OR = 2.5, 95% CI = 1.22-5.1, p = 0.012), while PD-L1 overexpression was not correlated with sex, tumor grade, lymph node status, and multifocality. Conclusions: The meta-analysis suggested that PD-L1 overexpression could predict worse survival outcomes in bladder cancer. High PD-L1 expression may act as a potential prognostic marker for patients with bladder cancer.

Methods: Alzheimer's disease and Frontotemporal dementia are the first and third most common forms of dementia. Due to their similar clinical symptoms, they are easily misdiagnosed as each other even with sophisticated clinical guidelines. For disease-specific intervention and treatment, it is essential to develop a computer-aided system to improve the accuracy of their differential diagnosis. Recent advances in deep learning have delivered some of the best performance for medical image recognition tasks. However, its application to the differential diagnosis of AD and FTD pathology has not been explored. Approach: In this study, we proposed a novel deep learning based framework to distinguish between brain images of normal aging individuals and subjects with AD and FTD. Specifically, we combined the multi-scale and multi-type MRI-base image features with Generative Adversarial Network data augmentation technique to improve the differential diagnosis accuracy. Results: Each of the multi-scale, multitype, and data augmentation methods improved the ability for differential diagnosis for both AD and FTD. A 10-fold cross validation experiment performed on a large sample of 1,954 images using the proposed framework achieved a high overall accuracy of 88.28%. Conclusions: The salient contributions of this study are three-fold: (1) our experiments demonstrate that the combination of multiple structural features extracted at different scales with our proposed deep neural network yields superior performance than individual features; (2) we show that the use of Generative Adversarial Network for data augmentation could further improve the discriminant ability of the network regarding challenging tasks such as differentiating dementia sub-types; (3) and finally, we show that ensemble classifier strategy could make the network more robust and stable.

To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients.

We report on the ongoing project "PREDICT-ADFTD: Multimodal Imaging Prediction of AD/FTD and Differential Diagnosis" describing completed and future work supported by this grant. This project is a multi-site, multi-study collaboration effort with research spanning seven sites across the US and Canada. The overall goal of the project is to study neurodegeneration within Alzheimer's Disease, Frontotemporal Dementia, and related neurodegenerative disorders, using a variety of brain imaging and computational techniques to develop methods for the early and accurate prediction of disease and its course. The overarching goal of the project is to develop the earliest and most accurate biomarker that can differentiate clinical diagnoses to inform clinical trials and patient care. In its third year, this project has already completed several projects to achieve this goal, focusing on (1) structural MRI (2) machine learning and (3) FDG-PET and multimodal imaging. Studies utilizing structural MRI have identified key features of underlying pathology by studying hippocampal deformation that is unique to clinical diagnosis and also post-mortem confirmed neuropathology. Several machine learning experiments have shown high classification accuracy in the prediction of disease based on Convolutional Neural Networks utilizing MRI images as input. In addition, we have also achieved high accuracy in predicting conversion to DAT up to five years in the future. Further, we evaluated multimodal models that combine structural and FDG-PET imaging, in order to compare the predictive power of multimodal to unimodal models. Studies utilizing FDG-PET have shown significant predictive ability in the prediction and progression of disease.

No abstract available

The processing of emotional facial expressions is important for social functioning and is influenced by environmental factors, including early environmental experiences. Low socio-economic status (SES) is associated with greater exposure to uncontrollable stressors, including violence, as well as deprivation, defined as a lack or decreased complexity of expected environmental input. The current study examined amygdala and fusiform gyrus response to facial expressions in 207 early adolescents (mean age = 13.93 years, 63.3% female). Participants viewed faces displaying varying intensities of angry and happy faces during functional MRI. SES was assessed using the income-to-needs ratio (INR) and a measure of subjective social status. Cumulative exposure to violence was also assessed. When considered in isolation, only violence exposure was associated with heightened amygdala response to angry faces. When considered jointly, violence exposure and lower INR were both associated with increased amygdala response to angry faces and interacted, such that lower INR was associated with increased amygdala reactivity to anger only in those youth reporting no exposure to violence. This pattern of findings raises the possibility that greater amygdala reactivity to threat cues in children raised in low-SES conditions may arise from different factors associated with an economically-deprived environment.