Aquaporin 1, a potential therapeutic target for migraine with aura

The pathophysiology of migraine remains largely unknown. However, evidence regarding the molecules participating in the pathophysiology of migraine has been accumulating. Water channel proteins, known as aquaporins (AQPs), notably AQP-1 and AQP-4, appears to be involved in the pathophysiology of several neurological diseases. This review outlines newly emerging evidence indicating that AQP-1 plays an important role in pain signal transduction and migraine and could therefore serve as a potential therapeutic target for these diseases

Brevibacillin 2V, a Novel Antimicrobial Lipopeptide With an Exceptionally Low Hemolytic Activity

Bacterial non-ribosomally produced peptides (NRPs) form a rich source of antibiotics, including more than 20 of these antibiotics that are used in the clinic, such as penicillin G, colistin, vancomycin, and chloramphenicol. Here we report the identification, purification, and characterization of a novel NRP, i.e., brevibacillin 2V (lipo-tridecapeptide), from Brevibacillus laterosporus DSM 25. Brevibacillin 2V has a strong antimicrobial activity against Gram-positive bacterial pathogens (minimum inhibitory concentration = 2 mg/L), including difficult-to-treat antibiotic-resistant Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus. Notably, brevibacillin 2V has a much lower hemolytic activity (HC(50) > 128 mg/L) and cytotoxicity (CC(50) = 45.49 ± 0.24 mg/L) to eukaryotic cells than previously reported NRPs of the lipo-tridecapeptide family, including other brevibacillins, which makes it a promising candidate for antibiotic development. In addition, our results demonstrate that brevibacillins display a synergistic action with established antibiotics against Gram-negative bacterial pathogens. Probably due to the presence of non-canonical amino acids and D-amino acids, brevibacillin 2V showed good stability in human plasma. Thus, we identified and characterized a novel and promising antimicrobial candidate (brevibacillin 2V) with low hemolytic activity and cytotoxicity, which can be used either on its own or as a template for further total synthesis and modification

Brevibacillin 2V Exerts Its Bactericidal Activity via Binding to Lipid II and Permeabilizing Cellular Membranes

Lipo-tridecapeptides, a class of bacterial non-ribosomally produced peptides, show strong antimicrobial activity against Gram-positive pathogens, including antibiotic-resistant Staphylococcus aureus and Enterococcus spp. However, many of these lipo-tridecapeptides have shown high hemolytic activity and cytotoxicity, which has limited their potential to be developed into antibiotics. Recently, we reported a novel antimicrobial lipo-tridecapeptide, brevibacillin 2V, which showed no hemolytic activity against human red blood cells at a high concentration of 128 mg/L, opposite to other brevibacillins and lipo-tridecapeptides. In addition, brevibacillin 2V showed much lower cytotoxicity than the other members of the brevibacillin family. In this study, we set out to elucidate the antimicrobial mode of action of brevibacillin 2V. The results show that brevibacillin 2V acts as bactericidal antimicrobial agent against S. aureus (MRSA). Further studies show that brevibacillin 2V exerts its bactericidal activity by binding to the bacterial cell wall synthesis precursor Lipid II and permeabilizing the bacterial membrane. Combined solid-state NMR, circular dichroism, and isothermal titration calorimetry assays indicate that brevibacillin 2V binds to the GlcNAc-MurNAc moiety and/or the pentapeptide of Lipid II. This study provides an insight into the antimicrobial mode of action of brevibacillin 2V. As brevibacillin 2V is a novel and promising antibiotic candidate with low hemolytic activity and cytotoxicity, the here-elucidated mode of action will help further studies to develop it as an alternative antimicrobial agent

Analysis of high-speed angular ball bearing lubrication based on bi-directional fluid-solid coupling

The lubrication of angular contact ball bearings under high-speed motion conditions is particularly important to the working performance of rolling bearings. Combining the contact characteristics of fluid domain and solid domain, a lubrication calculation model for angular contact ball bearings is established based on the RNG k-ε method. The pressure and velocity characteristics of the bearing basin under the conditions of rotational speed, number of balls and lubricant parameters are analyzed, and the lubrication conditions and dynamics of the angular contact ball bearings under different working conditions are obtained. The results show that the lubricant film pressure will rise with increasing speed and viscosity of the lubricant. The number of balls affects the pressure and velocity distribution of the flow field inside the bearing but has a small effect on the values of the characteristic parameters of the bearing flow field. The established CFD model provides a new approach to study the effect of fluid flow on bearing performance in angular contact ball bearings

Response of microbial communities in the tobacco phyllosphere under the stress of validamycin

Validamycin, is classified as an environmentally friendly fungicide. It has high efficacy with little associated pollution risk, and it has been used in China on tobacco for many years especially during leaf spot season. To understand changes in microbial communities and functional aspects of the tobacco phyllosphere after exposure to validamycin, the chemical was sprayed on tobacco leaves during brown spot epidemic periods caused by Alternaria alternata, and asymptomatic and symptomatic leaves of tobacco were sampled at different times (0 day before, 5, 10, and 15 days after application). The fungal and bacterial population diversity and structure were revealed using Illumina NovaSeq PE250 high-throughput sequencing technology, and Biolog-ECO technology which analyzes the metabolic differences between samples by using different carbon sources as the sole energy source. The results showed that the microbial community structure of both asymptomatic and symptomatic tobacco leaves changed after the application of valproate, with the microbial community structure of the asymptomatic tobacco leaves being more strongly affected than that of the symptomatic leaves, and the diversity of bacteria being greater than that of fungi. Phyllosphere fungal diversity in asymptomatic leaves increased significantly after application, and bacterial abundance and diversity in both asymptomatic and symptomatic leaves first increased and then decreased. Validamycin treatment effectively reduced the relative abundance of Alternaria, Cladosporium, Kosakonia, and Sphingomonas in leaves showing symptoms of tobacco brown spot, while the relative abundance of Thanatephorus, Pseudomonas, and Massilia increased significantly after application. Furthermore, the ability to metabolize a variety of carbon sources was significantly reduced in both types of leaves after validamycin application, and both types had a weaker ability to metabolize α-Ketobutyric Acid after application. This study reveals phyllosphere micro-ecological changes in symptomatic and asymptomatic tobacco leaves during different periods after validamycin application and the effects on the metabolic capacity of phyllosphere microorganisms. It can provide some basis for exploring the effect of validamycin on the control of tobacco brown spot

Roles of bacterial extracellular vesicles in systemic diseases

Accumulating evidence suggests that in various systems, not all bidirectional microbiota–host interactions involve direct cell contact. Bacterial extracellular vesicles (BEVs) may be key participants in this interkingdom crosstalk. BEVs mediate microbiota functions by delivering effector molecules that modulate host signaling pathways, thereby facilitating host–microbe interactions. BEV production during infections by both pathogens and probiotics has been observed in various host tissues. Therefore, these vesicles released by microbiota may have the ability to drive or inhibit disease pathogenesis in different systems within the host. Here, we review the current knowledge of BEVs and particularly emphasize their interactions with the host and the pathogenesis of systemic diseases

Regional differences of physical fitness and overweight and obesity prevalence among college students before and after COVID-19 pandemic since the “double first-class” initiative in China

IntroductionPhysical fitness has been widely recognized as a powerful marker of health in children and adolescents, and it negatively affected by the COVID-19 pandemic. The construction of world-class universities and first-class disciplines, known as the “Double First-Class” Initiative (DFC), is a major commitment made by the Chinese government to adapt to changes in the educational environment, both domestically and internationally, in order to promote the development and practice of international higher education. The aim of the study was to look deep into the regional differences of physical fitness and overweight and obesity prevalence among college students before and after the COVID-19 pandemic since the DFC.MethodsThe original physical fitness parameters of students from 10 DFC universities and colleges in Central South China were downloaded from the official website of Chinese National Student Physical Fitness Database (CNSPFD) and then divided into 3 groups based on the pandemic periods: pre-pandemic (2019), the first year after pandemic outbreak (2020), and the second year after pandemic outbreak (2021). All the data were stored in Excel 2010, analyzed by SPSS 17.0, and plotted with ArcGIS 10.4.ResultsThe total “fail” percentage (from 9.19% in 2019 to 12.94% in 2021) and the prevalence of overweight and obesity in boys (from 22.53 to 29.25% in 2021) exhibited a continuous increase year by year, and among all the physical fitness indicators the score of strength in boys and endurance quality in all individuals were the lowest in overweight and obesity groups. Students with ‘fail’ rate developed from northern and northeastern province to southern areas from 2019 to 2021. For grade 2019th, overweight and obesity students who also failed the test had covered nationwide and the most affected areas including northeast, east, as well as central north in senior year. The distribution of overall fitness assessments in Hubei province was in accordance with the national data, and the overall scoring growths in both class of 2021st and 2022nd were measured with a negative increase (p < 0.01).ConclusionThe government and related functional departments should take into consideration the student regional sources, especially in western and northeast regions of China, and school polices and physical education (PE) teachers should pay more attention to put training efforts on endurance for all adolescents and strength for boys and the group of overweight and obesity who also failed in the standard test, when designing specific interventions to promote physical health and counteract the negative effects of COVID-19 pandemic in college students

Genetic Engineering of the Biosynthesis of Glycine Betaine Modulates Phosphate Homeostasis by Regulating Phosphate Acquisition in Tomato

Glycine betaine (GB), as a putative compatible substance, protects plants against the damaging effects of abiotic stresses. Phosphorus deficiency is one type of abiotic stress that is detrimental to plant growth. Maintenance of phosphate (Pi) homeostasis is crucial. This study demonstrates GB-regulated phosphate homeostasis in the tomato (Solanum lycopersicum cv. ‘Moneymaker’) transformed with the choline oxidase gene codA from Arthrobacter globiformis. The codA-transgenic lines displayed more resistance to low-phosphate stress. The data revealed that the wild-type plants were stunted and consistently retained less Pi than transgenic lines, especially when grown under low-phosphate conditions. This difference in Pi retention was attributable to the enhanced Pi uptake ability in the transgenic lines. The transgenic plants translocated more Pi into the plant cell due to the enhanced enzymatic activity of plasma membrane H+-ATPase and increased Pi/H+ co-transport, which improved Pi uptake. The differential expression of ‘PHO regulon’ genes further maintained intracellular Pi homeostasis. Furthermore, GB maintained a higher photosynthesis rate, thus increasing the production and translocation of sucrose via phloem loading to enhance plant response to low-phosphate stress. We conclude that GB mediates Pi uptake and translocation by regulating physiological and biochemical processes that promote adaptation to environmental changes in Pi availability. These processes eventually lead to better growth and development of the codA-transgenic lines. This finding will help to further elucidate the signaling mechanism of how GB perceives and transmits low-phosphate signals to alleviate Pi nutritional stress

On-Chip Super-Resolution Imaging with Fluorescent Polymer Films

Wide field of view (FOV), label-free super-resolution imaging is demonstrated using a specially designed waveguide chip that can illuminate a sample with multi-colour evanescent waves travelling along different directions. The method is enabled by a polymer fluorescent film which emits over a broad wavelength range. Its polygonal geometry ensures coverage over all illumination directions, enabling high fidelity image reconstruction whilst minimizing distortion and image blurring. By frequency shifting and iterative stitching of different spatial frequencies in Fourier space, the reconstruction of two dimensional samples is achieved without distortion over wide FOVs. The fabrication process is facile and compatible with conventional semiconductor-fabrication methods. The super-resolution chip (SRC) can thus be produced with high yield, offer opportunities for potential conjunction of super-resolution techniques integrated optical circuits or for the development of single-use diagnostic kits