133 research outputs found
Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis
Tissue fibrosis compromises organ function and occurs as a potential
long-term outcome in response to acute tissue injuries. Currently, lack of
mechanistic understanding prevents effective prevention and treatment of the
progression from acute injury to fibrosis. Here, we combined quantitative
experimental studies with a mouse kidney injury model and a computational
approach to determine how the physiological consequences are determined by the
severity of ischemia injury, and to identify how to manipulate Wnt signaling to
accelerate repair of ischemic tissue damage while minimizing fibrosis. The
study reveals that Wnt-mediated memory of prior injury contributes to fibrosis
progression, and ischemic preconditioning reduces the risk of death but
increases the risk of fibrosis. Furthermore, we validated the prediction that
sequential combination therapy of initial treatment with a Wnt agonist followed
by treatment with a Wnt antagonist can reduce both the risk of death and
fibrosis in response to acute injuries
Dismantling the Black Box: Understanding Consumers\u27 Motivations for the Usage of Live Streaming Shopping Platform
Capturing consumers’ motivations for using the live streaming shopping platform (LSSP) can help guide the optimization of the platform and enhance shopping experience of consumers while watching live videos. Previous studies on user motivation typically explored technical and psychological antecedents of usage by considering the platform holistically. However, this black-box like treatment to the platform blurs the finer-grained details of consumer usage. This study takes a micro-level approach, disassembling the LSSP into 13 representative design features, and refines nine user motivations based on the uses and gratifications theory. Through collecting 237 questionnaires and employing regression analysis, we reveal the nuanced relationship between platform design features and consumer motivations. Our findings show that different design features are driven by distinct motivations, diverging from overall LSSP usage motivations. This research broadens the scope of LSSP studies, improves platform functionality, and offers practical insights for service providers
Transcriptome Phase Distribution Analysis Reveals Diurnal Regulated Biological Processes and Key Pathways in Rice Flag Leaves and Seedling Leaves
Plant diurnal oscillation is a 24-hour period based variation. The correlation between diurnal genes and biological pathways was widely revealed by microarray analysis in different species. Rice (Oryza sativa) is the major food staple for about half of the world's population. The rice flag leaf is essential in providing photosynthates to the grain filling. However, there is still no comprehensive view about the diurnal transcriptome for rice leaves. In this study, we applied rice microarray to monitor the rhythmically expressed genes in rice seedling and flag leaves. We developed a new computational analysis approach and identified 6,266 (10.96%) diurnal probe sets in seedling leaves, 13,773 (24.08%) diurnal probe sets in flag leaves. About 65% of overall transcription factors were identified as flag leaf preferred. In seedling leaves, the peak of phase distribution was from 2:00am to 4:00am, whereas in flag leaves, the peak was from 8:00pm to 2:00am. The diurnal phase distribution analysis of gene ontology (GO) and cis-element enrichment indicated that, some important processes were waken by the light, such as photosynthesis and abiotic stimulus, while some genes related to the nuclear and ribosome involved processes were active mostly during the switch time of light to dark. The starch and sucrose metabolism pathway genes also showed diurnal phase. We conducted comparison analysis between Arabidopsis and rice leaf transcriptome throughout the diurnal cycle. In summary, our analysis approach is feasible for relatively unbiased identification of diurnal transcripts, efficiently detecting some special periodic patterns with non-sinusoidal periodic patterns. Compared to the rice flag leaves, the gene transcription levels of seedling leaves were relatively limited to the diurnal rhythm. Our comprehensive microarray analysis of seedling and flag leaves of rice provided an overview of the rice diurnal transcriptome and indicated some diurnal regulated biological processes and key functional pathways in rice
Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms
BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles
Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.This work is part of the ‘‘SpatioTemporal Omics Consortium’’ (STOC) paper package. A list of STOC members is available at: http://sto-consortium.org. We would
like to thank the MOTIC China Group, Rongqin Ke (Huaqiao University, Xiamen,
China), Jiazuan Ni (Shenzhen University, Shenzhen, China), Wei Huang (Center
for Excellence in Brain Science and Intelligence Technology, Chinese Academy
of Sciences, Shanghai, China), and Jonathan S. Weissman (Whitehead Institute,
Boston, USA) for their help. This work was supported by the grant of Top Ten
Foundamental Research Institutes of Shenzhen, the Shenzhen Key Laboratory
of Single-Cell Omics (ZDSYS20190902093613831), and the Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011); Longqi Liu
was supported by the National Natural Science Foundation of China
(31900466) and Miguel A. Esteban’s laboratory at the Guangzhou Institutes of
Biomedicine and Health by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), National Natural Science Foundation of China (92068106), and the Guangdong Basic and Applied Basic Research
Foundation (2021B1515120075).S
Real-time Monitoring for the Next Core-Collapse Supernova in JUNO
Core-collapse supernova (CCSN) is one of the most energetic astrophysical
events in the Universe. The early and prompt detection of neutrinos before
(pre-SN) and during the SN burst is a unique opportunity to realize the
multi-messenger observation of the CCSN events. In this work, we describe the
monitoring concept and present the sensitivity of the system to the pre-SN and
SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is
a 20 kton liquid scintillator detector under construction in South China. The
real-time monitoring system is designed with both the prompt monitors on the
electronic board and online monitors at the data acquisition stage, in order to
ensure both the alert speed and alert coverage of progenitor stars. By assuming
a false alert rate of 1 per year, this monitoring system can be sensitive to
the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos
up to about 370 (360) kpc for a progenitor mass of 30 for the case
of normal (inverted) mass ordering. The pointing ability of the CCSN is
evaluated by using the accumulated event anisotropy of the inverse beta decay
interactions from pre-SN or SN neutrinos, which, along with the early alert,
can play important roles for the followup multi-messenger observations of the
next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure
Household, community, sub-national and country-level predictors of primary cooking fuel switching in nine countries from the PURE study
Introduction. Switchingfrom polluting (e.g. wood, crop waste, coal)to clean (e.g. gas, electricity) cooking
fuels can reduce household air pollution exposures and climate-forcing emissions.While studies have
evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role
of different multilevel factors in household fuel switching, outside of interventions and across diverse
community settings, is not well understood. Methods.We examined longitudinal survey data from
24 172 households in 177 rural communities across nine countries within the Prospective Urban and
Rural Epidemiology study.We assessed household-level primary cooking fuel switching during a
median of 10 years offollow up (∼2005–2015).We used hierarchical logistic regression models to
examine the relative importance of household, community, sub-national and national-level factors
contributing to primary fuel switching. Results. One-half of study households(12 369)reported
changing their primary cookingfuels between baseline andfollow up surveys. Of these, 61% (7582)
switchedfrom polluting (wood, dung, agricultural waste, charcoal, coal, kerosene)to clean (gas,
electricity)fuels, 26% (3109)switched between different polluting fuels, 10% (1164)switched from clean
to polluting fuels and 3% (522)switched between different clean fuels
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