Colorectal cancer (CRC) is a gastrointestinal malignancy originating from either the colon or the rectum. A growing number of researches prove that the unfolded protein response (UPR) is closely ...related to the occurrence and progression of colorectal cancer. The UPR has three canonical endoplasmic reticulum (ER) transmembrane protein sensors: inositol requiring kinase 1 (IRE1), pancreatic ER eIF2α kinase (PERK), and activating transcription factor 6 (ATF6). Each of the three pathways is closely associated with CRC development. The three pathways are relatively independent as well as interrelated. Under ER stress, the activated UPR boosts the protein folding capacity to maximize cell adaptation and survival, whereas sustained or excessive ER triggers cell apoptosis conversely. The UPR involves different stages of CRC pathogenesis, promotes or hinders the progression of CRC, and will pave the way for novel therapeutic and diagnostic approaches. Meanwhile, the correlation between different signal branches in UPR and the switch between the adaptation and apoptosis pathways still need to be further investigated in the future.
Display omitted
Emerging studies have investigated potential cardiovascular and respiratory health impacts from the use of personal-level intervention equipment against air pollution exposure. The ...objective of this systematic review is to assess the efficacy of personal-level air pollution intervention on mitigating adverse health effects from air pollution exposure by using portable air cleaner or wearing respirator.
In this systematic review, we searched PubMed and Web of Science for published literatures up to May 31, 2020, focusing on personal-level air pollution intervention studies. Among these studies, we investigated the impacts on cardio-respiratory responses to the use of these interventions. The intervention of review interest was the use of personal-level equipment against air pollution, including using portable air cleaner indoors or wearing respirator outdoors. The outcome of review interest was impacts on cardio-respiratory health endpoints following interventions, including level changes in blood pressure, heart rate variability (HRV), lung function, and biomarkers of inflammation and oxidative stress. Weighted mean differences or percent changes were pooled in meta-analyses for these health endpoints. The heterogeneity across studies was assessed using the Cochran's Q-statistic test, and the individual study quality was assessed using the Cochrane risk of bias tool version 2 (RoB 2). We further applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to evaluate the certainty of evidence.
From systematic literature search and screening, we identified 29 related eligible intervention studies, including 21 studies on indoor portable air cleaner use and 8 studies on respirator use. For portable air cleaner intervention, we observed suggestive evidence of beneficial changes on cardio-respiratory health endpoints. Collectively in these studies, we found significantly beneficial changes of 2.01% decreases (95% CI: 0.50%, 3.52%) in systolic blood pressure, as well as non-significantly beneficial changes of 3.04% increases (95% CI: -2.65%, 8.74%) in reactive hyperemia index and 0.24% increases (95% CI: −0.82%, 1.31%) in forced expiratory volume in 1 s. We also observed non-significant reductions in levels of inflammation and oxidative stress biomarkers, including C-reactive protein, interleukin-6, fibrinogen, fractional exhaled nitric oxide and malondialdehyde. For respirator intervention, we observed some beneficial changes on cardiovascular health endpoints, such as significant increases in HRV parameters SDNN (2.20%, 95% CI: 0.54%, 3.86%), as well as non-significant decreases in blood pressure SBP (0.63 mmHg, 95% CI: −0.39, 1.66); however, no sufficient data were available for meta-analyses on lung function and biomarkers. RoB 2 assessments suggested that most intervention studies were with a moderate to high overall risk of bias. The certainty of evidence for intervention outcome pairs was graded very low for either portable air cleaner or respirator intervention. The common reasons to downgrade study evidence included loss to follow-up, lack of blinding, lack of washout period, small sample size, and high heterogeneity across studies.
The uses of indoor portable air cleaner and respirator could contribute to some beneficial changes on cardiovascular health, but with much limited evidence on respiratory health. Low certainty of the overall study evidence shed light on future research for larger sample size trials with more rigorous study design.
Accurate species identification and abundance estimation are critical for the interpretation of whole metagenome sequencing (WMS) data. Yet, existing metagenomic profilers suffer from false-positive ...identifications, which can account for more than 90% of total identified species. Here, by leveraging species-specific Type IIB restriction endonuclease digestion sites as reference instead of universal markers or whole microbial genomes, we present a metagenomic profiler, MAP2B (MetAgenomic Profiler based on type IIB restriction sites), to resolve those issues. We first illustrate the pitfalls of using relative abundance as the only feature in determining false positives. We then propose a feature set to distinguish false positives from true positives, and using simulated metagenomes from CAMI2, we establish a false-positive recognition model. By benchmarking the performance in metagenomic profiling using a simulation dataset with varying sequencing depth and species richness, we illustrate the superior performance of MAP2B over existing metagenomic profilers in species identification. We further test the performance of MAP2B using real WMS data from an ATCC mock community, confirming its superior precision against sequencing depth. Finally, by leveraging WMS data from an IBD cohort, we demonstrate the taxonomic features generated by MAP2B can better discriminate IBD and predict metabolomic profiles.
The gut microbiota plays a pivotal role in upholding intestinal health, fostering intestinal development, fortifying organisms against pathogen intrusion, regulating nutrient absorption, and managing ...the body’s lipid metabolism. However, the influence of different cultivation modes on the growth indices and intestinal microbes of Salmo trutta fario remains underexplored. In this study, we employed high-throughput sequencing and bioinformatics techniques to scrutinize the intestinal microbiota in three farming modes: traditional pond aquaculture (TPA), recirculating aquaculture (RA), and flow-through aquaculture (FTA). We aimed to assess the impact of different farming methods on the water environment and Salmo trutta fario’s growth performance. Our findings revealed that the final weight and weight gain rate in the FTA model surpassed those in the other two. Substantial disparities were observed in the composition, relative abundance, and diversity of Salmo trutta fario gut microbiota under different aquaculture modes. Notably, the dominant genera of Salmo trutta fario gut microbiota varied across farming modes: for instance, in the FTA model, the most prevalent genera were SC-I-84 (7.34%), Subgroup_6 (9.93%), and UTCFX1 (6.71%), while, under RA farming, they were Bacteroidetes_vadinHA17 (10.61%), MBNT15 (7.09%), and Anaeromyxoactor (6.62%). In the TPA model, dominant genera in the gut microbiota included Anaeromyxobacter (8.72%), Bacteroidetes_vadinHA17 (8.30%), and Geobacter (12.54%). From a comparative standpoint, the genus-level composition of the gut microbiota in the RA and TPA models exhibited relative similarity. The gut microbiota in the FTA model showcased the most intricate functional diversity, while TPA farming displayed a more intricate interaction pattern with the gut microbiota. Transparency, pH, dissolved oxygen, conductivity, total dissolved solids, and temperature emerged as pivotal factors influencing Salmo trutta fario gut microbiota under diverse farming conditions. These research findings offer valuable scientific insights for fostering healthy aquaculture practices and disease prevention and control measures for Salmo trutta fario, holding substantial significance for the sustainable development of the cold-water fish industry in the Qinghai–Tibet Plateau.
Pseudorabies virus (PRV), which is extremely infectious and can infect numerous mammals, has a risk of spillover into humans. Virus-host interactions determine viral entry and spreading. Here, we ...showed that neuropilin-1 (NRP1) significantly potentiates PRV infection. Mechanistically, NRP1 promoted PRV attachment and entry, and enhanced cell-to-cell fusion mediated by viral glycoprotein B (gB), gD, gH, and gL. Furthermore, through
coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays, NRP1 was found to physically interact with gB, gD, and gH, and these interactions were C-end Rule (CendR) motif independent, in contrast to currently known viruses. Remarkably, we illustrated that the viral protein gB promotes NRP1 degradation via a lysosome-dependent pathway. We further demonstrate that gB promotes NRP1 degradation in a furin-cleavage-dependent manner. Interestingly, in this study, we generated gB furin cleavage site (FCS)-knockout PRV (Δfurin PRV) and evaluated its pathogenesis;
, we found that Δfurin PRV virulence was significantly attenuated in mice. Together, our findings demonstrated that NRP1 is an important host factor for PRV and that NRP1 may be a potential target for antiviral intervention.
Recent studies have shown accelerated PRV cross-species spillover and that PRV poses a potential threat to humans. PRV infection in humans always manifests as a high fever, tonic-clonic seizures, and encephalitis. Therefore, understanding the interaction between PRV and host factors may contribute to the development of new antiviral strategies against PRV. NRP1 has been demonstrated to be a receptor for several viruses that harbor CendR, including SARS-CoV-2. However, the relationships between NRP1 and PRV are poorly understood. Here, we found that NRP1 significantly potentiated PRV infection by promoting PRV attachment and enhanced cell-to-cell fusion. For the first time, we demonstrated that gB promotes NRP1 degradation via a lysosome-dependent pathway. Last,
, Δfurin PRV virulence was significantly attenuated in mice. Therefore, NRP1 is an important host factor for PRV, and NRP1 may be a potential target for antiviral drug development.
The effects of ultrasonic treatment on grain refinement and hydrogen removal in three kinds of magnesium alloys—Mg-3Ca, Mg-6Zn-1Ca, and AZ80 alloys—were investigated in this study. After ultrasonic ...treatment, the grains of the magnesium alloys were refined to varying degrees. The degassing effect was characterized by measuring the densities and hydrogen content of ingots. The results indicated that the application of ultrasonic treatment in these magnesium alloys was able to remove hydrogen and obviously refine the microstructure. In this experiment, both the measurement of the density of the ingots and the solid-state hydrogen measurement reflected the degree of degassing. The highest degassing efficiencies were 53.8%, 67.5%, and 34.9% for the Mg-3Ca, Mg-6Zn-1Ca, and AZ80 alloys, respectively. The lowest hydrogen content of the AZ80 alloy reached 8.2 cm3/100 g, and the corresponding tensile strengths were 174 Mpa, 79 Mpa, and 6.2%, which represented increases of 41.5%, 38.6%, and 87.9%, respectively. The cavitation effect and acoustic streaming effect with an appropriate ultrasonic treatment duration resulted in grain refinement, degassing, and the uniform dispersion of second phases. This can significantly improve mechanical properties and provide a basis for industrial production.
MicroRNAs (miRNAs) play an essential role in tumor biological processes through interacting with specific gene targets. The involvement of miR-195-5p in cell proliferation, invasion, and migration ...has been demonstrated in several cancer cell lines, while its function in oral squamous cell carcinoma (OSCC) remains unclear. Here we find that miR-195-5p expression is lower in OSCC than in nontumor tissues, while its overexpression in cell lines can lead to the promotion of apoptosis and the reduction of cell growth, migration, and invasion. Moreover, we identify the tripartite motif-containing protein (TRIM14) as a target of miR-195-5p. Therefore, we reason that the tumor suppressor role of miR-195-5p in OSCC is dependent on the interaction with TRIM14.
This paper studies the range equation modeling of a ground moving target for multichannel medium-Earth-orbit (MEO) synthetic aperture radar (SAR) ground moving target indication (GMTI), an issue ...which is challenging to tackle due to the non-linear motion of the radar platform and the Earth rotation. In the paper, the coordinates of the multichannel MEO SAR and the target, as well as the target’s range equation with respect to each channel, are developed. Moreover, an expression of concise form is derived for the target’s quadratic-approximated range equation, which will benefit the design of GMTI methods. Furthermore, theoretical analyses are conducted to reveal the dependency between the accuracy of the quadratic-approximated range equation and the parameters of the radar and the target. Numerical simulations are carried out to investigate the influence of the quadratic approximation of the range equation on the GMTI performance and to figure out the quadratic-approximated range equation’s scope of application.
This longitudinal cohort study investigated the associations of air pollutant exposures, including CO, NO, NO
, NO
, O
, PM
, PM
, and SO
, with long-term kidney function changes in patients with ...chronic kidney disease (CKD). We enrolled 447 CKD patients who took part in a universal hospital pre-ESRD care program during 2011-2015. The daily average air pollutant exposures and temperature were estimated for each patient, with different levels of air pollutant concentrations defined by 5-knot and restricted cubic spline function. Predicted annual estimated glomerular filtration (eGFR) slope values by one mixed model were considered as the study outcome. The average age of the study population was 77.1 ± 12.6 years, and the median annual eGFR decreased by 2.1 ml/min/1.73 m
per year from 30 ml/min/1.73 m
at baseline during a mean follow-up time of 3.4 years. The univariable and multivariable analyses revealed no significant linear and non-linear associations between 5-knot air pollutant concentrations and annual eGFR slope. In addition, the visualized spline effect plots show insignificant variation patterns in annual eGFR slope values with increased air pollutant concentrations. These results encourage more extensive studies to clarify the causal relationships and mechanisms of long-term specific air pollutant exposures and longitudinal kidney function change, especially in CKD populations.
PDF
