DNA Checkpoint and Repair Factors Are Nuclear Sensors for Intracellular Organelle Stresses-Inflammations and Cancers Can Have High Genomic Risks.

Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF) and DNA damage repair factors (DDRF) play a vital role in maintaining genomic integrity. However, how DDCFs and DDRFs are modulated under physiological and pathological conditions are not fully known. We took an experimental database analysis to determine the expression of 26 DNA D

Design and Experiments on Droplet Charging Device for High-Range Electrostatic Sprayer

Non

Mechanical Analysis of 3D Composite Materials by Hybrid Boundary Node Method

In this paper, an improved multi-domain model based on the hybrid boundary node method (Hybrid BNM) is proposed for mechanical analysis of 3D composites. The Hybrid BNM is a boundary type meshless method which based on the modified variational principle and the Moving Least Squares (MLS) approximation. The improved multi-domain model can reduce the total degrees of freedom (DOFs) compared with the conventional multi-domain solver. It is very suitable for the inclusion-based composites, especially for the composites when the inclusions are solid and totally embedded in the matrix domain. Numerical examples are presented to verify the improved multi-domain model and the results have shown the accuracy and efficiency of the improved model

Exceeding probability analysis for rail of high-speed railway under seismic excitations

Purpose – The smoothness of the high-speed railway (HSR) on the bridge may exceed the allowable standard when an earthquake causes vibrations for HSR bridges, which may threaten the safety of running trains. Indeed, few studies have evaluated the exceeding probability of rail displacement exceeding the allowable standard. The purposes of this article are to provide a method for investigating the exceeding probability of the rail displacement of HSRs under seismic excitation and to calculate the exceeding probability. Design/methodology/approach – In order to investigate the exceeding probability of the rail displacement under different seismic excitations, the workflow of analyzing the smoothness of the rail based on incremental dynamic analysis (IDA) is proposed, and the intensity measure and limit state for the exceeding probability analysis of HSRs are defined. Then a finite element model (FEM) of an assumed HSR track-bridge system is constructed, which comprises a five-span simply-supported girder bridge supporting a finite length CRTS II ballastless track. Under different seismic excitations, the seismic displacement response of the rail is calculated; the character of the rail displacement is analyzed; and the exceeding probability of the rail vertical displacement exceeding the allowable standard (2mm) is investigated. Findings – The results show that: (1) The bridge-abutment joint position may form a step-like under seismic excitation, threatening the running safety of high-speed trains under seismic excitations, and the rail displacements at mid-span positions are bigger than that at other positions on the bridge. (2) The exceeding probability of rail displacement is up to about 44% when PGA = 0.01g, which is the level-five risk probability and can be described as 'very likely to happen'. (3) The exceeding probability of the rail at the mid-span positions is bigger than that above other positions of the bridge, and the mid-span positions of the track-bridge system above the bridge may be the most hazardous area for the running safety of trains under seismic excitation when high-speed trains run on bridges. Originality/value – The work extends the seismic hazardous analysis of HSRs and would lead to a better understanding of the exceeding probability for the rail of HSRs under seismic excitations and better references for the alert of the HSR operation

Multi-omics insights into beagle dog fed with a sucking-rewarded automatic feeding device

BackgroundFacilitating the development of the sucking function in early stages of preterm infants holds substantial potential for influencing their long-term outcomes. To this end, our team has devised a sucking-rewarded automatic feeding device specifically tailored for preterm infants. The present study is designed to investigate the impacts of this innovative device, utilizing a multi-omics profiling approach, on beagle dogs as a surrogate model.MethodsThis study involved seven-day-old male newborn beagle puppies, carefully selected and matched in terms of body weights. The participants were stratified into two groups: the experimental group (AFG, sucking-rewarded feeding group) and the control group (PFG). After a 14-day intervention period, fecal and blood samples were systematically collected from each dog. The collected samples were then subjected to distinct profiling analyses, encompassing the assessment of gut microbial composition, plasma metabolic profiles, and proteomic expression profiles.ResultsThe gut microbial data showed a significant difference between the AFG and PFG groups based on Bray-Curtis dissimilarity (P = 0.048), and the relative abundance of Lactobacillus was significantly more abundant in the AFG group compared to the PFG group. The significantly different metabolites between the two groups were enriched in functional metabolic pathways related to amino acids, fatty acid metabolism, and the nervous system. Notably, neurotransmitter L-glutamic acid was significantly up-regulated in the AFG group. Moreover, the significantly different proteins between the two groups were enriched in GO terms related to oxygen transport, oxygen binding, iron ion binding, hemoglobin complex, and heme binding. Among them, proteins A0A8C0MTD2, P60524, P60529 were significantly up-regulated in the AFG group. Notably, Lactobacillus, L-glutamic acid, A0A8C0MTD2, P60524, and P60529 were correlated with each other through correlation analysis, these molecules play important roles in the neural function and neurodevelopment.ConclusionOur investigation elucidated discernible modifications in gut microbial composition, plasma metabolic profiles, and proteomic expression patterns in beagle dogs subjected to the sucking-rewarded automatic feeding device

A triton X-100 assisted PMAxx-qPCR assay for rapid assessment of infectious African swine fever virus

IntroductionAfrican Swine Fever (ASF) is a highly infectious disease of pigs, caused by African swine fever virus (ASFV). The lack of vaccines and drugs makes strict disinfection practices to be one of the main measurements to curb the transmission of ASF. Therefore, it is important to assess if all viruses are inactivated after disinfection or after long time exposure in their natural conditions. Currently, the infectivity of ASFV is determined by virus isolation and culture in a biosafety level 3 (BSL-3) laboratory. However, BSL-3 laboratories are not readily available, need skilled expertise and may be time consuming.MethodsIn this study, a Triton X-100 assisted PMAxx-qPCR method was developed for rapid assessment of infectious ASFV in samples. PMAxx, an improved version of propidium monoazide (PMA), can covalently cross-link with naked ASFV-DNA or DNA inside inactivated ASFV virions under assistance of 0.1% (v/v) TritonX-100, but not with ASFV-DNA inside live virions. Formation of PMAxx-DNA conjugates prevents PCR amplification, leaving only infectious virions to be detected. Under optimum conditions, the limit of detection of the PMAxx-qPCR assay was 2.32log10HAD50/mL of infectious ASFV. Testing different samples showed that the PMAxx-qPCR assay was effective to evaluate intact ASFV virions after treatment by heat or chemical disinfectants and in simulated samples such as swine tissue homogenate, swine saliva swabs, and environmental swabs. However, whole-blood and saliva need to be diluted before testing because they may inhibit the PCR reaction or the cross-linking of PMAxx with DNA.ConclusionThe Triton X-100 assisted PMAxx-qPCR assay took less than 3 h from sample to result, offering an easier and faster way for assessing infectious ASFV in samples from places like pig farms and pork markets

Effectiveness of β-blockers in improving 28-day mortality in septic shock: insights from subgroup analysis and retrospective observational study

BackgroundIn recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment.MethodsThis retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups.ResultsA total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment.ConclusionWe found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research

BackgroundGut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases.MethodsThirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates.ResultsThe combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10−3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10−3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10−2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10−2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10−3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity.ConclusionThis study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions