Polymorphisms of STAT-6, STAT-4 and IFN-γ genes and the risk of asthma in Chinese population

SummaryBackgroundAsthma is a complex disease resulting from multiple gene–gene and gene–environment interactions. Study on gene–gene interactions could provide insight into the pathophysiologic mechanisms of the disease.ObjectivesWe investigated the single nucleotide polymorphisms and interactions among three different loci in three candidate genes (STAT-6 G2964A, STAT-4 T90089C and IFN-γ T874A) in 95 Chinese asthmatic subjects and 95 matched controls to determine the possible associations with asthma.MethodsGenotyping of the gene polymorphisms was performed by means of PCR-SSCP analysis. Genotype–phenotype associations were examined in dominant and recessive genetic models using logistic regression. The method of multifactor dimensionality reduction was used to analyze gene–gene interactions.ResultsNo statistically significant difference was found in the distribution of the STAT-6 G2964A polymorphisms between asthmatic patients and controls in this case–control study. The STAT-4 T90089C polymorphisms were significantly associated with asthma in the dominant model (p=0.007). As for the IFN-γ T874A, the significant associations were found in both dominant model (p=0.004) and recessive model (p=0.006). A significant gene–gene interaction was found among STAT-6, STAT-4 and IFN-γ on the risk of asthma. In the best 3-locus model, the odds ratio for the high-risk to the low-risk group was 6.9 (95% CI, 3.5–13.7; p<0.0001).ConclusionsOur findings suggest that STAT-4 T90089C and IFN-γ T874A polymorphisms might be the genetic factors for the risk of asthma in the Chinese population. In addition, the significant interactions among STAT-6 G2964A, STAT-4 T90089C and IFN-γ T874A may increase an individual's susceptibility and contribute to the pathogenesis of asthma

Molecular characterization, structural analysis and determination of host range of a novel bacteriophage LSB-1

<p>Abstract</p> <p>Background</p> <p>Bacteriophages (phages) are widespread in the environment and play a crucial role in the evolution of their bacterial hosts and the emergence of new pathogens.</p> <p>Results</p> <p>LSB-1, a reference coliphage strain, was classified as a member of the Podoviridae family with a cystic form (50 ± 5 nm diameter) and short tail (60 ± 5 nm long). The double stranded DNA was about 30 kilobase pairs in length. We identified its host range and determined the gp17 sequences and protein structure using shotgun analysis and bioinformatics technology.</p> <p>Conclusions</p> <p>Coliphage LSB-1 possesses a tailspike protein with endosialidase activity which is probably responsible for its specific enteroinvasive <it>E.coli </it>host range within the laboratory.</p

Impact-based probabilistic modeling of hydro-morphological processes in China (1985–2015)

Hydro-morphological processes (HMP, any natural phenomenon contained within the spectrum defined between debris flows and flash floods) pose a relevant threat to infrastructure, urban and rural settlements and to lives in general. This has been widely observed in recent years and will likely become worse as climate change will influence the spatio-temporal pattern of precipitation events. The modelling of where HMP-driven hazards may occur can help define the appropriate course of actions before and during a crisis, reducing the potential losses that HMPs cause in their wake. However, the probabilistic information on locations prone to experience a given hazard is not sufficient to depict the risk our society may incur. To cover this aspect, modeling the loss information could open up to better territorial management strategies. In this work, we made use of the HMP catalogue of China from 1985 to 2015. Specifically, we implemented the Light Gradient Boosting (LGB) classifier to model the impact level that locations across China have suffered from HMPs over the thirty-year record. We obtained six impact levels as a combination of financial and life losses, whose classes we used as separate target variables for our LGB. In doing so, we estimated spatial probabilities of certain HMP impact, something that has yet to be tested in the natural hazard community, especially over such a large spatial domain. The results we obtained are encouraging, with each of the six impact categories being separately classified with excellent to outstanding performance (the worst case corresponds to a mean AUC = 0.862, whereas the best case corresponds to a mean AUC of 0.915). The good predictive performance our model produced suggest that the cartographic output could be useful to inform authorities of locations prone to human and infrastructural losses of specific magnitudes.</p

Blue-Sky Albedo Reduction and Associated Influencing Factors of Stable Land Cover Types in the Middle-High Latitudes of the Northern Hemisphere during 1982–2015

Land surface albedo (LSA) directly affects the radiation balance and the surface heat budget. LSA is a key variable for local and global climate research. The complexity of LSA variations and the driving factors highlight the importance of continuous spatial and temporal monitoring. Snow, vegetation and soil are the main underlying surface factors affecting LSA dynamics. In this study, we combined Global Land Surface Satellite (GLASS) products and ERA5 reanalysis products to analyze the spatiotemporal variation and drivers of annual mean blue-sky albedo for stable land cover types in the middle-high latitudes of the Northern Hemisphere (30~90°N) from 1982 to 2015. Snow cover (SC) exhibited a decreasing trend in 99.59% of all pixels (23.73% significant), with a rate of −0.0813. Soil moisture (SM) exhibited a decreasing trend in 85.66% of all pixels (22.27% significant), with a rate of −0.0002. The leaf area index (LAI) exhibited a greening trend in 74.38% of all pixels (25.23% significant), with a rate of 0.0014. Blue-sky albedo exhibited a decreasing trend in 98.97% of all pixels (65.12% significant), with a rate of −0.0008 (OLS slope). Approximately 98.16% of all pixels (57.01% significant) exhibited a positive correlation between blue-sky albedo and SC. Approximately 47.78% and 67.38% of all pixels (17.13% and 25.3% significant, respectively) exhibited a negative correlation between blue-sky albedo and SM and LAI, respectively. Approximately 10.31%, 20.81% and 68.88% of the pixel blue-sky albedo reduction was mainly controlled by SC, SM and LAI, respectively. The decrease in blue-sky albedo north of 40°N was mainly caused by the decrease in SC. The decrease in blue-sky albedo south of 40°N was mainly caused by SM reduction and vegetation greening. The decrease in blue-sky albedo in the western Tibetan Plateau was caused by vegetation greening, SM increase and SC reduction. The results have important scientific significance for the study of surface processes and global climate change

Identification of a Novel COL4A4 Variant in Compound-Heterozygous State in a Patient With Alport Syndrome and Histological Findings Similar to Focal Segmental Glomerulosclerosis (FSGS)

Alport syndrome (AS) is a rare and inherited renal disorder with an autosomal recessive mode of inheritance. AS patients usually manifest with hematuria and progressive renal disorder also occasionally accompanied by hearing loss and ophthalmic disease. Germline variants in collagen type IV α-4 (COL4A4) gene lead to autosomal recessive Alport syndrome. In the present study, we investigated a Chinese family with Alport syndrome. The index patient is a 24-year-old Chinese woman who has been suffering from proteinuria. Renal biopsy and renal pathology were performed and found focal segmental glomerulosclerosis (FSGS) like lesion in the index patient. The index patient also presented with binocular edema and blurred vision. However, binocular edema dissipated gradually without any further treatment. Unlikely, the index patient was not diagnosed with hearing impairment. Index patient’s parents are phenotypically normal. Targeted next generation sequencing and Sanger sequencing was performed. A novel heterozygous single nucleotide insertion, c.4760_4761insC and a previously reported likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC in the COL4A4 gene were identified in the index patient. The novel heterozygous single nucleotide insertion (c.4760_4761insC) leads to a frameshift which eventually results in the formations of a truncated COL4A4 protein. In addition, the other heterozygous likely pathogenic variant, c.1323_1340delTGGCTTGCCTGGAGCACC, has been already identified with causing AS an autosomal recessive mode of inheritance. Sanger sequencing confirmed that these two variants were inherited in the index patient from her father and mother, respectively. These two variants were not found in 100 normal control individuals. In conclusion, our present finding emphasizes the significance of high throughput targeted next generation sequencing technology for rapid and cost-effective genetic screening which allows us easy and accurate clinical diagnosis of AS patients

CVT: A Crowdsourcing Video Transcoding Scheme Based on Blockchain Smart Contracts

Streaming media has been largely used by millions of users every day. The number of customers and programs, e.g., TV series, movies, and various shows, are still growing fast. However, the demand for video transcoding for various personal terminal devices results in the shortage of computing resources and the prolongation of processing delay in centralized video transcoding systems. To solve this issue, we propose a blockchain, especially, smart contract based scheme that can achieve decentralized and on-demand crowdsourcing for video transcoding, which remarkably mitigates the transcoding overhead. Specifically, our scheme consists of four key components such as employers, workers, task allocation, and payment. An employer initializes the smart contract, releases the task, and initiates the smart contract. Workers bid for the task, and the successful bidder will obtain the task and execute the task. The task allocation mechanism and the payment mechanism can guarantee the profits of both and encourage both as well. Moreover, the smart contract consists of the bidding contract and the task execution contract. The extensive analysis of our proposed scheme justified the feasibility, security for defending against typical threats, applicability in realistic situations, and portability for most multimedia such as videos and audios

BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases

Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings

Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis

Normal aging is typically characterized by abnormal resting-state functional connectivity (FC), including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals (N = 36, ages 20–25 for the young group; N = 32, ages 60–85 for the senior group) were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms