Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophages via the UNC5B-Akt/mTOR axis

Upon migrating into the tissues, hematopoietic stem cell (HSC)-derived monocytes differentiate into macrophages, playing a crucial role in determining innate immune responses towards external pathogens and internal stimuli. However, the regulatory mechanisms underlying monocyte-to-macrophage differentiation remain largely unexplored. Here we divulge a previously uncharacterized but essential role for an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), in monocyte-to-macrophage maturation. FLRT2 is almost undetectable in human monocytic cell lines, human peripheral blood mononuclear cells (PBMCs), and mouse primary monocytes but significantly increases in fully differentiated macrophages. Myeloid-specific deletion of FLRT2 (Flrt2ΔMyel) contributes to decreased peritoneal monocyte-to-macrophage generation in mice in vivo, accompanied by impaired macrophage functions. Gain- and loss-of-function studies support the promoting effect of FLRT2 on THP-1 cell and human PBMC differentiation into macrophages. Mechanistically, FLRT2 directly interacts with Unc-5 netrin receptor B (UNC5B) via its extracellular domain (ECD) and activates Akt/mTOR signaling. In vivo administration of mTOR agonist MYH1485 reverses the impaired phenotypes observed in Flrt2ΔMyel mice. Together, these results identify FLRT2 as a novel pivotal endogenous regulator of monocyte differentiation into macrophages. Targeting the FLRT2/UNC5B-Akt/mTOR axis may provide potential therapeutic strategies directly relevant to human diseases associated with aberrant monocyte/macrophage differentiation

Oregano essential oil modulates colonic homeostasis and intestinal barrier function in fattening bulls

Oregano essential oil (OEO) primarily contains phenolic compounds and can serve as a dietary supplement for fattening bulls. However, the precise molecular mechanism underlying this phenomenon remains largely elusive. Therefore, this study investigated the impact of adding OEO to diet on the integrity of the intestinal barrier, composition of the colonic microbiome, and production of microbial metabolites in fattening bulls. Our goal was to provide insights into the utilization of plant essential oil products in promoting gastrointestinal health and welfare in animals. We employed amplicon sequencing and metabolome sequencing techniques to investigate how dietary supplementation with OEO impacted the intestinal barrier function in bulls. The inclusion of OEO in the diet resulted in several notable effects on the colon of fattening bulls. These effects included an increase in the muscle thickness of the colon, goblet cell number, short-chain fatty acid concentrations, digestive enzyme activity, relative mRNA expression of intestinal barrier-related genes, and relative expression of the anti-inflammatory factor IL-10. Additionally, α-amylase activity and the relative mRNA expression of proinflammatory cytokines decreased. Moreover, dietary OEO supplementation increased the abundance of intestinal Bacteroides, Coprobacillus, Lachnospiraceae_UCG_001, and Faecalitalea. Metabolomic analysis indicated that OEO primarily increased the levels of 5-aminovaleric acid, 3-methoxysalicylic acid, and creatinine. In contrast, the levels of maltose, lactulose, lactose, and D-trehalose decreased. Correlation analysis showed that altered colonic microbes and metabolites affected intestinal barrier function. Taken together, these results demonstrate that OEO facilitates internal intestinal environmental homeostasis by promoting the growth of beneficial bacteria while inhibiting harmful ones

H2S gas sensing performance and mechanisms using CuO-Al2O3 composite films based on both surface acoustic wave and chemiresistor techniques

Surface acoustic wave and chemiresistor based gas sensors integrated with a sensing layer of sol-gel CuO-Al2O3 composite film were fabricated and their performance and mechanisms for H2S sensing were characterized and compared. In the composite film, CuO nanoparticles provide active sites for adsorption and reaction of H2S molecules while Al2O3 nanoparticles help to form a uniform and mesoporous film structure, both of which enhance the sensitivity of the sensors by providing numerous active CuO surfaces. Through the comparative studies, the SAW based H2S sensor operated at room temperature showed a lower detection limit, higher sensitivity, better linearity and good selectivity to H2S gas with its concentration ranging from 5 ppb to 100 ppm, compared with those of the chemiresistor sensor, which are mainly attributed to the effective mass sensing properties of the SAW sensor, because a minor change in the mass of the film caused by adsorbed H2S molecules would lead to a significant and monotonous change of the resonant frequency of the SAW devices

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Spatiotemporal Distribution and Influencing Factors of the Net Primary Productivity in the Datai Mine in Western Beijing

In the context of those countries around the world that are actively promoting sustainable development of the environment, China has formulated a new “double carbon” strategic goal to assume corresponding responsibilities. Vegetation carbon sequestration plays a key role in enhancing the carbon sink capacity toward reaching the carbon peak and carbon neutrality. In order to quantitatively study vegetation carbon sequestration, in this article, we used the net primary productivity (NPP) as an indicator to measure it. In this research, the Datai Coal Mine in western Beijing was used as the study area, and the spatiotemporal distribution characteristics and the influencing factors of carbon sequestration through vegetation were analyzed. Based on the meteorological data, remote sensing images, and the land use data of the mining area, the improved Carnegie–Ames–Stanford Approach (CASA) was used to calculate the net primary productivity (NPP) of vegetation in the Datai mining area from 2013 to 2021, to analyze its temporal and spatial distribution in relation to meteorological factors. The results showed that in the past 9 years, the NPP in the Datai mining area generally increased from 546 gC/m2 to 601 gC/m2. The NPP in the Mentougou District generally decreased and had a significant relationship with precipitation, temperature, and solar radiation. The Mentougou District’s NPP change had a significant positive correlation with the precipitation change (R2 = 0.8). The Mentougou District’s NPP change had no significant relationship with temperature (R2 = 0.98) and solar radiation fluctuations (R2 = 0.75). In conclusion, the vegetation NPP in the Datai Mine regularly changed throughout the year, and its annual vegetation NPP was about twice that of the Mentougou District, which probably due to the low-intensity mining of the Datai Mine. Thus, there is no significant impact on the vegetation carbon in this area

Cooperative Transmission Mechanism Based on Revenue Learning for Vehicular Networks

With the rapid development of science and technology and the improvement of people’s living standards, vehicles have gradually become the main means of travel. The increase in vehicles has also brought about an increasing incidence of car accidents. In order to reduce traffic accidents, many researchers have proposed the use of vehicular networks to quickly transmit information. As long as these vehicles can receive information from other vehicles or buildings nearby in a timely manner, they can avoid accidents. In vehicular networks, the traditional double connection technique, through interference coordination scheduling strategy based on graph theory, can ensure the fairness of vehicles and obtain suitable neighborhood interference resistance with limited computing resources. However, when a base station transmits data to the vehicular user, the nearby base station and the vehicular network user may be in a state of suspended communication. Thus, the resource utilization of the above double connection vehicular network is not sufficient, resulting in a waste of resources. To solve this issue, this paper presents a study based on earnings learning with a vehicular network multi-point collaborative transmission mechanism, in which the vehicular network users communicate with the surrounding collaborative transmission. We use the Q-learning algorithm in the reinforcement learning process to enable vehicular network users to learn from each other and make cooperative decisions in different environments. In reinforcement learning, the agent makes a decision and changes the state of the environment. Then, the environment feeds back the benefit to the agent through the related algorithm so that the agent gradually learns the optimal decision. Simulation results demonstrate the superiority of our proposed approach with the revenue machine learning model compared with the benchmark schemes

Nicotine Elevated Intracellular Ca 2+

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca2+ concentration ([Ca2+]i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca2+]i in airway smooth muscle cells (ASMCs). Methods: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. Results: RT-PCR analysis showed that α2-7, β2, and β3-nAChR subunits are expressed in rat ASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca2+]i in cultured rat ASMCs. Acute application of nicotine evoked a rapid increase in [Ca2+]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 µM nicotine for 48 hours. Nicotine-induced Ca2+ response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca2+ responses induced by nicotine. Conclusion: These observations suggest that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling