Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing

Motivation: Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures. Results: The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the superior performance of Dr Insight over several popular drug-repurposing methods to detect known cancer drugs and drug–target interactions. A proof-of-concept trial using the TCGA breast cancer dataset demonstrates the application of Dr Insight for a comprehensive analysis, from redirection of drug therapies, to a systematic construction of disease-specific drug-target networks

Association of Blood Pressure With Stroke Risk, Stratified by Age and Stroke Type, in a Low-Income Population in China: A 27-Year Prospective Cohort Study

Association of stroke risk with new blood pressure criterion 2017 is unknown in China. We assessed the association between blood pressure (BP) values and stroke risk in a low-income population in Tianjin, China. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were categorized into five strata and strokes were recorded as stroke, ischemic stroke, and hemorrhagic stroke. Stroke risk was analyzed according to blood pressure stratum using Cox regression analysis. Overall, 4,017 residents (age, ≥18 years) were included in this prospective cohort study. Over a 27-year follow-up period (total, 86,515.78 person-years), 638 participants experienced first-ever strokes. The stroke risk was higher among individuals with SBPs ≥140 mmHg or DBPs ≥90 mmHg than among those with SBPs < 130 mmHg or DBPs < 80 mmHg (reference group), after adjusting for covariates. However, hemorrhagic stroke risk increased only in participants with SBPs ≥160 mmHg. The stroke risk increased for individuals < 65-years-old having BP values ≥130/80 mmHg and for individuals ≥65-years-old with BP values ≥160/90 mmHg. To reduce the stroke burden in China, target BP goals must be established for adults, with different targets for the middle-aged and the elderly segments of the population. These results are very important for guiding clinical practice and may be generalized to other developing countries experiencing rapid economic development and where transitions in the spectrum of prevalent diseases have occurred

Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells.

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells\u27 biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation

Radial Growth Response of Larix gmelinii to Climate along a Latitudinal Gradient in the Greater Khingan Mountains, Northeastern China

To explore how climatic factors influence tree growth within the context of global climate changes, we used a dendroclimatological analysis to understand the response of Larix gmelinii to climatic variations along a broad latitudinal gradient from 47.27 degrees to 52.66 degrees N in the Greater Khingan Mountains of Northeastern China. The growth-limiting climate factors and a detailed association between radial growth and climate were identified along the gradient using redundancy analysis (RDA) and standard correlation function analysis over the period 1960-2013. The results showed that temperatures during current June to July represented the most important factor affecting tree radial growth in the study area. Across all studied latitudes, Larix gmelinii growth might be decreasing in radial growth due to higher monthly maximum temperature (Tmax) and monthly mean temperatures (Tm) in the current June, especially for the stands at low and middle latitudes. With continued warming, Larix gmelinii radial growth at high latitudes (e.g., Mangui (MG) and Mohe (MH)) might be reduced by warmer temperatures in July. In addition, Larix gmelinii might be decreasing in radial growth from decreasing precipitation. Our results show that there is a decreasing trend in Larix gmelinii radial growth under the observed general increase of temperatures in the Greater Khingan Mountains in recent years.Peer reviewe

Atomic-layered Au clusters on α-MoC as catalysts for the low-temperature water-gas shift reaction

The water-gas shift (WGS) reaction (where carbon monoxide plus water yields dihydrogen and carbon dioxide) is an essential process for hydrogen generation and carbon monoxide removal in various energy-related chemical operations. This equilibrium-limited reaction is favored at a low working temperature. Potential application in fuel cells also requires a WGS catalyst to be highly active, stable, and energy-efficient and to match the working temperature of on-site hydrogen generation and consumption units. We synthesized layered gold (Au) clusters on a molybdenum carbide (α-MoC) substrate to create an interfacial catalyst system for the ultralow-temperature WGS reaction. Water was activated over α-MoC at 303 kelvin, whereas carbon monoxide adsorbed on adjacent Au sites was apt to react with surface hydroxyl groups formed from water splitting, leading to a high WGS activity at low temperatures