Understanding the potential drivers for respiratory syncytial virus rebound during the COVID-19 pandemic

Non-pharmaceutical interventions (NPIs) were widely introduced to combat the COVID-19 pandemic. These interventions also likely led to substantially reduced activity of respiratory syncytial virus (RSV). From late 2020, some countries observed out-of-season RSV epidemics. Here, we analyzed the role of NPIs, population mobility, climate, and SARS-CoV-2 circulation in RSV rebound through a time-to-event analysis across 18 countries. Full (re)-opening of schools was associated with an increased risk for RSV rebound (HR = 23.29 [95% CI: 1.09–495.84]); every 5°C increase in temperature was associated with a decreased risk (HR = 0.63 [0.40–0.99]). There was an increasing trend in the risk for RSV rebound over time, highlighting the role of increased population susceptibility. No other factors were found statistically significant. Further analysis suggests increasing population susceptibility and full (re)-opening of schools could both override the counter-effect of high temperatures, which explains the out-of-season RSV epidemics during the COVID-19 pandemic

Effect of ecological restoration programs on dust concentrations in the North China Plain: a case study

In recent decades, the Chinese government has made a great effort in initiating large-scale ecological restoration programs (ERPs) to reduce the dust concentrations in China, especially for dust storm episodes. Using the Moderate Resolution Imaging Spectroradiometer (MODIS) land cover product, the ERP-induced land cover changes are quantitatively evaluated in this study. Two obvious vegetation protective barriers arise throughout China from the southwest to the northeast, which are well known as the "Green Great Wall" (GGW). Both the grass GGW and forest GGW are located between the dust source region (DSR) and the densely populated North China Plain (NCP). To assess the effect of ERPs on dust concentrations, a regional transport/dust model (WRF-DUST, Weather Research and Forecast model with dust) is applied to investigate the evolution of dust plumes during a strong dust storm episode from 2 to 8 March 2016. The WRF-DUST model generally performs reasonably well in reproducing the temporal variations and spatial distributions of near-surface [PMC] (mass concentration of particulate matter with aerodynamic diameter between 2.5 and 10 mu m) during the dust storm event. Sensitivity experiments have indicated that the ERP-induced GGWs help to reduce the dust concentration in the NCP, especially in BTH (Beijing, Tianjin, and Hebei). When the dust storm is transported from the upwind DSR to the downwind NCP, the [PMC] reduction ranges from -5 to -15% in the NCP, with a maximum reduction of -12.4% (-19.2 mu gm(3)) in BTH and -7.6% (-10.1 mu g m(3)) in the NCP. We find the dust plumes move up to the upper atmosphere and are transported from the upwind DSR to the downwind NCP, accompanied by dust decrease. During the episode, the forest GGW is nonsignificant in dust concentration control because it is of benefit for dry deposition and not for emission. Conversely, the grass GGW is beneficial in controlling dust erosion and is the dominant reason for [PMC] decrease in the NCP. Because the air pollution is severe in eastern China, especially in the NCP, and the contribution of dust episodes is significant, the reduction of dust concentrations will have important effects on severe air pollution. This study illustrates the considerable contribution of ERPs to the control of air pollution in China, especially in springtime

High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy

Resistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell's radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.Peer reviewe

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment

Inflammatory Bowel Disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Though the pathogenesis of IBD remains unclear, diet is increasingly recognized as a pivotal factor influencing its onset and progression. Fatty acids, essential components of dietary lipids, play diverse roles in IBD, ranging from anti-inflammatory and immune-regulatory functions to gut-microbiota modulation and barrier maintenance. Short-chain fatty acids (SCFAs), products of indigestible dietary fiber fermentation by gut microbiota, have strong anti-inflammatory properties and are seen as key protective factors against IBD. Among long-chain fatty acids, saturated fatty acids, trans fatty acids, and ω-6 polyunsaturated fatty acids exhibit pro-inflammatory effects, while oleic acid and ω-3 polyunsaturated fatty acids display anti-inflammatory actions. Lipid mediators derived from polyunsaturated fatty acids serve as bioactive molecules, influencing immune cell functions and offering both pro-inflammatory and anti-inflammatory benefits. Recent research has also highlighted the potential of medium- and very long-chain fatty acids in modulating inflammation, mucosal barriers, and gut microbiota in IBD. Given these insights, dietary intervention and supplementation with short-chain fatty acids are emerging as potential therapeutic strategies for IBD. This review elucidates the impact of various fatty acids and lipid mediators on IBD and delves into potential therapeutic avenues stemming from these compounds

Independent Association of Serum Fibroblast Growth Factor 21 Levels With Impaired Liver Enzymes in Hyperthyroid Patients

Fibroblast growth factor 21 (FGF21) is identified as a potential biomarker for liver diseases. However, information is limited regarding serum FGF21 and impaired liver function in hyperthyroidism. We aim to determine the potential association of serum FGF21 levels with impaired liver enzymes in hyperthyroid patients. In this case-control study, 105 normal subjects and 122 overt hyperthyroid patients were included. Among them, 41 hyperthyroid patients who obtained euthyroid status after thionamide treatment received second visit. Serum FGF21 levels were determined using the ELISA method. Compared to the normal subjects, patients with hyperthyroidism had significantly elevated serum liver enzymes, including alanine transaminase (ALT) (p < 0.001), aspartate aminotransferase (AST) (p < 0.001) levels, as well as FGF21 levels (p < 0.001). Further analysis showed serum FGF21 (p < 0.05), as well as thyroid hormone (TH) free T3 (p < 0.05), free T4 (p < 0.05) levels were higher in hyperthyroid patients with impaired liver enzymes than in those with normal liver enzymes. After reversal of hyperthyroid state, elevated serum FGF21 levels in hyperthyroid patients declined significantly (p < 0.001), with a concomitant decrease in serum ALT (p < 0.001), AST (p < 0.001) levels. Correlation analysis showed close correlation between FGF21 and ALT (p < 0.002), AST (p < 0.012), free T3 (p < 0.001), free T4 (p < 0.001). Further logistic regression analysis revealed FGF21 is significantly associated with elevated ALT [Odds Ratio, OR 1.79, (95% confidence interval, CI), (1.30–2.47), P < 0.001], AST [1.59 (1.07–2.34), p < 0.020]. After adjustment of potential confounders, the association between FGF21 and elevated ALT remained significant [1.42 (1.01–1.99), p < 0.043]. In conclusion, serum FGF21 is independently associated with impaired liver enzymes in hyperthyroid patients

N6-Methyladenosine and Viral Infection

N6-methyladenosine (m6A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m6A. Multiple m6A-modified viral RNAs have been observed. The epitranscriptome of m6A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m6A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m6A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m6A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m6A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m6A in distinct viral infection. Given the increasingly important roles of m6A in diverse viruses, m6A represents a novel potential target for antiviral therapy

Deletion of Exon 20 of the Familial Dysautonomia Gene Ikbkap in Mice Causes Developmental Delay, Cardiovascular Defects, and Early Embryonic Lethality

Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP - the protein encoded by Ikbkap - remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data