Spatial-linked alignment tool (SLAT) for aligning heterogenous slices.

Spatially resolved omics technologies reveal the spatial organization of cells in various biological systems. Here we propose SLAT (Spatially-Linked Alignment Tool), a graph-based algorithm for efficient and effective alignment of spatial slices. Adopting a graph adversarial matching strategy, SLAT is the first algorithm capable of aligning heterogenous spatial data across distinct technologies and modalities.

Moderate Alcohol Use Is Associated with Reduced Cardiovascular Risk in Middle-Aged Men Independent of Health, Behavior, Psychosocial, and Earlier Life Factors.

We examined whether the often-reported protective association of alcohol with cardiovascular disease (CVD) risk could arise from confounding. Our sample comprised 908 men (56−67 years), free of prevalent CVD. Participants were categorized into 6 groups: never drinkers, former drinkers, and very light (1−4 drinks in past 14 days), light (5−14 drinks), moderate (15−28 drinks), and at-risk (>28 drinks) drinkers.

Machine Learning Applied to Omics Datasets Predicts Mortality in Patients with Alcoholic Hepatitis.

Alcoholic hepatitis is a major health care burden in the United States due to significant morbidity and mortality. Early identification of patients with alcoholic hepatitis at greatest risk of death is extremely important for proper treatments and interventions to be instituted. In this study, we used gradient boosting, random forest, support vector machine and logistic regression analysis of laboratory parameters, fecal bacterial microbiota, fecal mycobiota, fecal virome, serum metabolome and serum lipidome to predict mortality in patients with alcoholic hepatitis.

Identifying complex motifs in massive omics data with a variable-convolutional layer in deep neural network.

Motif identification is among the most common and essential computational tasks for bioinformatics and genomics. Here we proposed a novel convolutional layer for deep neural network, named variable convolutional (vConv) layer, for effective motif identification in high-throughput omics data by learning kernel length from data adaptively. Empirical evaluations on DNA-protein binding and DNase footprinting cases well demonstrated that vConv-based networks have superior performance to their convolutional counterparts regardless of model complexity.

Expectation pooling: an effective and interpretable pooling method for predicting DNA-protein binding.

Motivation: Convolutional neural networks (CNNs) have outperformed conventional methods in modeling the sequence specificity of DNA-protein binding. While previous studies have built a connection between CNNs and probabilistic models, simple models of CNNs cannot achieve sufficient accuracy on this problem. Recently, some methods of neural networks have increased performance using complex neural networks whose results cannot be directly interpreted.

Causal effects of informal care and health on falls and other accidents among the elderly population in China.

Purpose: This article analyzes the causal effects of informal care, mental health, and physical health on falls and other accidents (e.g., traffic accidents) among elderly people.

Simian genogroup I picobirnaviruses: prevalence, genetic diversity, and zoonotic potential.

We previously reported the first detection of simian picobirnaviruses (PBVs) by polyacrylamide gel electrophoresis in fecal specimens of two monkeys with diarrhea in China. We now report the detection of genogroup I PBVs in 48% (44/92) of the fecal specimens by reverse transcriptase PCR (RT-PCR) and amplicon sequencing using primers specific for the RNA-dependent RNA polymerase (RDRP) gene. Molecular characterization of these 44 strains demonstrated both sequence conservation and diversity among simian PBVs and among simian, porcine, and human PBVs.

Characterization of the spike protein of human coronavirus NL63 in receptor binding and pseudotype virus entry.

The spike (S) protein of human coronavirus NL63 (HCoV-NL63) mediates both cell attachment by binding to its receptor hACE2 and membrane fusion during virus entry. We have previously identified the receptor-binding domain (RBD) and residues important for RBD-hACE2 association. Here, we further characterized the S protein by investigating the roles of the cytoplasmic tail and 19 residues located in the RBD in protein accumulation, receptor binding, and pseudotype virus entry.

[Construction of lentiviral mediated CyPA siRNA and its functions in non-small cell lung cancer].

Objective: To construct a lentiviral-vector-mediated CyPA small interference RNA (siRNA) and study its function in non-small cell lung cancer.

Methods: First, four target sequences were selected according to CyPA mRNA sequence, the complementary DNA contained both sense and antisense oligonucleotides were designed, synthesized and cloned into the pGCL-GFP vector, which contained U6 promoter and green fluorescent protein (GFP). The resulting lentiviral vector containing CyPA shRNA was named Lv-shCyPA, and it was confirmed by PCR and sequencing.

Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques.

Angiotensin converting enzyme 2 (ACE2) is the receptor that severe acute respiratory syndrome coronavirus (SARS-CoV) utilizes for target cell entry and, therefore, plays an important role in SARS pathogenesis. Since Chinese rhesus (rh) macaques do not usually develop SARS after SARS-CoV infection, it has been suggested that rh-ACE2 probably does not support viral entry efficiently. To determine the role of rh-ACE2 in early lung pathogenesis in vivo, we studied eleven Chinese rhesus monkeys experimentally infected with a pathogenic SARS-CoV(PUMC01) strain.

Detection of viral agents in fecal specimens of monkeys with diarrhea.

Background: Diarrheal disease is a major cause of morbidity and mortality in humans and animals, including non human primates. While the diagnostics for gastrointestinal bacterial and parasitic pathogens and their etiological role in disease are well established, little is known about the epidemiology, prevalence and role of viral agents in diarrheal illness among monkeys.

Methods: We collected fecal specimens from monkeys with diarrhea that were housed in two primate colonies, the Institute of Laboratory Animal Sciences, Beijing, China and the Yerkes National Primate Research Center, Georgia, USA.

[Preventive and therapeutic effects of recombinant IFN-alpha2b nasal spray on SARS-CoV infection in Macaca mulata].

Objective: To study the preventive and therapeutic effects of recombinant IFN-alpha2b for nasal spray on SARS-CoV infection in Macaca mulata (rhesus monkey).

Methods: Ten rhesus monkeys were divided into two groups, 5 in interferon group, and 5 in control group. Before and after SARS-CoV attack, the virus was detected in samples such as pharyngeal swab in all the two groups by Real-time PCR (RT-PCR) and virus isolation was performed.

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation.

Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region.

Immunization with a killed or inactivated viral vaccine provides significant protection in animals against challenge with certain corresponding pathogenic coronaviruses (CoVs). However, the promise of this approach in humans is hampered by serious concerns over the risk of leaking live severe acute respiratory syndrome (SARS) viruses. In this study, we generated a SARS vaccine candidate by using the live-attenuated modified vaccinia virus Ankara (MVA) as a vector.

[Potent neutralization antibody elicited in mice by SARS-associated coronavirus spike protein S1 domain].

Objective: To study the antigenicity of SARS associated coronavirus (CoV) spike S1 (12-672Aa) domain.

Methods: BALB/c mice were immunized with a plasmid bearing codon-optimized SARS-CoV (Tor2 strain) S1 domain and then boosted with purified S1 protein; the SARS-CoV specific IgG antibody was tested by ELISA and neutralization antibody was determined by in vitro microneutralization assay.

Results: S1 domain of SARS-CoV spike, which has been demonstrated harboring the receptor binding domain, successfully elicited SARS-CoV specific IgG antibody in mouse after combined immunization with DNA and purified S1 protein; the antibody elicited solely by S1 could potently neutralize SARS-CoV (HKU-39849) in vitro, 50% of 1 000 TCID50 SARS-CoV challenged cells were protected from viral infection by a 1:1499.