ABSTRACT Background Sustained pulmonary inflammation contributes significantly to lung carcinogenesis. Macrophages play a pivotal role in perpetuating inflammatory responses, undergoing a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis upon activation. The interplay between metabolic reprogramming and macrophage polarization remains poorly defined. The objective of this study is to examines the anti‐inflammatory mechanism of lipoic acid (LA), focusing on its ability to modulate immunometabolism in activated macrophages. Methods We utilized lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages and a murine acute lung injury (ALI) model to evaluate the anti‐inflammatory effects of LA. Inflammatory cytokine expression was assessed by qPCR, ELISA, and Western blot. Metabolic profiling was performed using Seahorse XF technology to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), evaluating glycolytic and oxidative metabolic functions. Results This study systematically elucidates the molecular mechanism by which LA modulates macrophage inflammatory responses through targeting the HIF1α/glycolysis axis. The main findings are as follows: (1) In LPS‐induced RAW264.7 macrophages, LA treatment significantly inhibited the expression of M1 macrophage markers (iNOS, CD86) and the secretion of proinflammatory cytokines (IL‐1β, IL‐6, etc.). (2) LA effectively reduced the expression of GSDMD, the key executor of pyroptosis, demonstrating its inhibitory effect on macrophage pyroptosis. (3) Metabolic analysis revealed that LA reversed LPS‐induced metabolic reprogramming by decreasing the ECAR and increasing the OCR, thereby suppressing glycolysis. (4) Mechanistic studies showed that siRNA‐mediated knockdown of HIF1α replicated both the anti‐inflammatory and metabolic regulatory effects of LA, confirming HIF1α as the key target in this pathway. (5) In an ALI mouse model, LA treatment significantly reduced HIF1α expression in lung tissues and effectively alleviated inflammatory responses, further validating the proposed mechanism. Conclusion LA exerts potent anti‐inflammatory effects by targeting HIF1α‐mediated metabolic reprogramming in macrophages. Our results highlight the therapeutic potential of targeting immunometabolic pathways in inflammatory lung diseases, providing new insights into the mechanism by which LA ameliorates pulmonary inflammation.
Movement monitoring with wearable technologies is becoming increasingly popular in different fields of application (clinical, sports, entertainment). Particularly, textile-based wearables for movement monitoring are attractive as they follow the body movement, are comfortable to use, and can provide continuous tracking capabilities. Ideally, these wearable devices should be flexible (as opposed to current technologies with rigid electronics on the garments) and transmit data wirelessly to avoid hindering the natural movement with connections. Although fully textile wireless and passive wearable systems — whereby the textile sensing part does not have any rigid components and the data is wirelessly transmitted to an external reader — have been developed, the capability of these technologies is currently limited to a single sensor. In this work, we present a system based on a resonating inductor-capacitor (LC) circuits that can measure multiple sensors to broaden the range of use by tracking more than a single joint. Importantly, the presented system employs multiple capacitive strain sensors but retains the use of a single inductor for data transmission, limiting the complexity of realization and the number of connections. After characterization on the bench for careful design of the circuit components, we demonstrated the capability of the system to be used for human movement monitoring and activity classification by integrating two sensors in sport leggings and performing different static and dynamic activities. The tests with sensorized leggings were performed by a single participant. Among a set of chosen classification algorithms, the best performance (F1-score) was 0.98 for the static activities and 0.96 for dynamic activities. When including three independent sessions (donning and doffing the sensorised leggings) accuracy and F1-score dropped to 0.86 and 0.87 respectively. Overall, the presented system has the potential to be adopted as unobtrusive and comfortable smart clothing for real time movement monitoring.
Accurate, high-throughput estimation of Above-Ground Biomass (AGB), a key predictor of yield, is a critical goal in rapeseed breeding. However, this is constrained by two key challenges: (1) traditional measurement is destructive and laborious, and (2) modern deep learning approaches require vast, costly labeled datasets. To address these issues, we present a data-efficient deep learning framework using smartphone-captured top-down RGB images for AGB estimation (Fresh Weight, FW, and Dry Weight, DW). Our approach utilizes a two-stage strategy where a Vision Transformer (ViT) backbone is first pre-trained on a large, aggregated dataset of diverse, non-rapeseed public plant datasets using the DINOv2 self-supervised learning (SSL) method. Subsequently, this pre-trained model is fine-tuned on a small, custom-labeled rapeseed dataset (N = 833) using a Multi-Task Learning (MTL) framework to simultaneously regress both FW and DW. This MTL approach acts as a powerful regularizer, forcing the model to learn robust features related to the 3D plant structure and density. Through rigorous 5-fold cross-validation, our proposed model achieved strong predictive performance for both Fresh Weight (Coefficient of Determination, R<sup>2</sup> = 0.842) and Dry Weight (R<sup>2</sup> = 0.829). The model significantly outperformed a range of baselines, including models trained from scratch and those pre-trained on the generic ImageNet dataset. Ablation studies confirmed the critical and synergistic contributions of both domain-specific SSL (vs. ImageNet) and the MTL framework (vs. single-task training). This study demonstrates that an SSL+MTL framework can effectively learn to infer complex 3D plant attributes from 2D images, providing a robust and scalable tool for non-destructive phenotyping to accelerate the rapeseed breeding cycle.
Abstract Background Enterococcus faecium and E. lactis are phylogenetically closely related lactic acid bacteria that are ubiquitous in nature and are known to be beneficial or pathogenic. Despite their considerable industrial and clinical importance, comprehensive studies on their evolutionary relationships and genomic, metabolic, and pathogenic traits are still lacking. Therefore, we conducted comparative pangenome analyses using all available dereplicated genomes of these species. Results E. faecium was divided into two subclades: subclade I, comprising strains derived from humans, animals, and food, and the more recent phylogenetic subclade II, consisting exclusively of human-derived strains. In contrast, E. lactis strains, isolated from diverse sources including foods, humans, animals, and the environment, did not display distinct clustering based on their isolation sources. Despite having similar metabolic features, noticeable genomic differences were observed between E. faecium subclades I and II, as well as E. lactis. Notably, E. faecium subclade II strains exhibited significantly larger genome sizes and higher gene counts compared to both E. faecium subclade I and E. lactis strains. Furthermore, they carried a higher abundance of antibiotic resistance, virulence, bacteriocin, and mobile element genes. Phylogenetic analysis of antibiotic resistance and virulence genes suggests that E. faecium subclade II strains likely acquired these genes through horizontal gene transfer, facilitating their effective adaptation in response to antibiotic use in humans. Conclusions Our study offers valuable insights into the adaptive evolution of E. faecium strains, enabling their survival as pathogens in the human environment through horizontal gene acquisitions.
Abstract After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.
Abstract Phagocytosis, a vital defense mechanism, involves the recognition and elimination of foreign substances by cells. Phagocytes, such as neutrophils and macrophages, rapidly respond to invaders; macrophages are especially important in later stages of the immune response. They detect “find me” signals to locate apoptotic cells and migrate toward them. Apoptotic cells then send “eat me” signals that are recognized by phagocytes via specific receptors. “Find me” and “eat me” signals can be strategically harnessed to modulate antitumor immunity in support of cancer therapy. These signals, such as calreticulin and phosphatidylserine, mediate potent pro‐phagocytic effects, thereby promoting the engulfment of dying cells or their remnants by macrophages, neutrophils, and dendritic cells and inducing tumor cell death. This review summarizes the phagocytic “find me” and “eat me” signals, including their concepts, signaling mechanisms, involved ligands, and functions. Furthermore, we delineate the relationships between “find me” and “eat me” signaling molecules and tumors, especially the roles of these molecules in tumor initiation, progression, diagnosis, and patient prognosis. The interplay of these signals with tumor biology is elucidated, and specific approaches to modulate “find me” and “eat me” signals and enhance antitumor immunity are explored. Additionally, novel therapeutic strategies that combine “find me” and “eat me” signals to better bridge innate and adaptive immunity in the treatment of cancer patients are discussed.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Abstract Background Subacute ruminal acidosis (SARA) is a common metabolic disorder of high yielding dairy cows, and it is associated with dysbiosis of the rumen and gut microbiome and host inflammation. This study evaluated the impact of two postbiotics from Saccharomyces cerevisiae fermentation products (SCFP) on rumen liquid associated microbiota of lactating dairy cows subjected to repeated grain-based SARA challenges. A total of 32 rumen cannulated cows were randomly assigned to 4 treatments from 4 weeks before until 12 weeks after parturition. Treatment groups included a Control diet or diets supplemented with postbiotics (SCFPa, 14 g/d Original XPC; SCFPb-1X, 19 g/d NutriTek; SCFPb-2X, 38 g/d NutriTek, Diamond V, Cedar Rapids, IA, USA). Grain-based SARA challenges were conducted during week 5 (SARA1) and week 8 (SARA2) after parturition by replacing 20% DM of the base total mixed ration (TMR) with pellets containing 50% ground barley and 50% ground wheat. Total DNA from rumen liquid samples was subjected to V3–V4 16S rRNA gene amplicon sequencing. Characteristics of rumen microbiota were compared among treatments and SARA stages. Results Both SARA challenges reduced the diversity and richness of rumen liquid microbiota, altered the overall composition (β-diversity), and its predicted functionality including carbohydrates and amino acids metabolic pathways. The SARA challenges also reduced the number of significant associations among different taxa, number of hub taxa and their composition in the microbial co-occurrence networks. Supplementation with SCFP postbiotics, in particular SCFPb-2X, enhanced the robustness of the rumen microbiota. The SCFP supplemented cows had less fluctuation in relative abundances of community members when exposed to SARA challenges. The SCFP supplementation promoted the populations of lactate utilizing and fibrolytic bacteria, including members of Ruminococcaceae and Lachnospiraceae, and also increased the numbers of hub taxa during non-SARA and SARA stages. Supplementation with SCFPb-2X prevented the fluctuations in the abundances of hub taxa that were positively correlated with the acetate concentration, and α- and β-diversity metrics in rumen liquid digesta. Conclusions Induction of SARA challenges reduced microbiota richness and diversity and caused fluctuations in major bacterial phyla in rumen liquid microbiota in lactating dairy cows. Supplementation of SCFP postbiotics could attenuate adverse effects of SARA on rumen liquid microbiota.
Gustavo Hiroshi Sera, Tumoru Sera, Valdir Mariucci Junior
et al.
IPR Pérola is a Coffea arabica cultivar developed from a cross between IAPAR 59 and Mundo Novo IAC 376-4. It features a dwarf-medium size, high yield, excellent cup quality, a medium-early ripening cycle, and large beans. Additionally, it boasts high resistance to coffee leaf rust.
A. Vetráková, R. Kalianková Chovanová, R. Rechtoríková
et al.
Bacillus subtilis spores are considered to be efficient and useful vehicles for the surface display and delivery of heterologous proteins. In this study, we prepared recombinant spores with the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein displayed on their surface in fusion with the CotZ or CotY spore coat proteins as a possible tool for the development of an oral vaccine against the SARS-CoV-2 virus. The RBD was attached to the N-terminus or C-terminus of the coat proteins. We also directly adsorbed non-recombinantly produced RBD to the spore surface. SDS-PAGE, western blot and fluorescence microscopy were used to analyze RBD surface expression on purified spores. Results obtained from both display systems, recombinant and non-recombinant, demonstrated that RBD was present on the spore surfaces.
Agnieszka Tajner-Czopek, Elżbieta Rytel, Agnieszka Kita
et al.
Potatoes with different flesh colours contain health-promoting compounds, i.e., hydroxycinnamic acids, which vary in content and stability during thermal processing. The aim of this study was to determine the effect of the technological stages of the production of French fries obtained from potatoes with different flesh colours on the content of selected hydroxycinnamic acids, as well as the stability of these acids, their percentage in sum of acids, total phenolic content and antioxidant activity (ABTS, DPPH) in semi-products and ready-to-eat products. During the production of French fries, samples of unpeeled, peeled, cut, blanched, pre-dried and fried potatoes were collected. After peeling, coloured potatoes, especially purple ones, had more hydroxycinnamic (5-CQA, 4-CQA, 3-CQA and CA) acids remaining in the flesh than in the flesh of the light-yellow variety. The greatest losses of the determined hydroxycinnamic acids, regardless of the given potato’s variety, were caused by the stage of pre-drying (about 91%) and frying (about 97%). The French fries obtained from the potatoes with coloured flesh, especially those with purple flesh, had the highest amount of stable 5-CQA and 4-CQA acids as well as 3-CQA acid, already absent in light-yellow French fries. The least stable acid was CA acid, which was not found in any of the ready snacks.
Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles. Methods This study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC–MS/MS analysis. Results A total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway, and response to lead ion were significantly enriched at week 2 and 4. Another four processes were only enriched at week 8, namely response to oxidative stress, positive regulation of cell proliferation, thyroid hormone generation, and positive regulation of apoptotic process. The PPI network indicated that these differential proteins were biologically connected in CS-exposed rats. Of the 79 differential proteins in CS-exposed rats, 56 had human orthologs. Seven proteins that had changed at week 2 and 4 when there were no changes of pulmonary function and pathological morphology were verified as potential biomarkers for early screening of CS-induced COPD by proteomic analysis. Another six proteins that changed at week 8 when obvious airflow obstruction was detected were verified as potential biomarkers for prognostic assessment of CS-induced COPD. Conclusions These results reveal that the urinary proteome could sensitively reflect pathological changes in CS-exposed rats, and provide valuable clues for exploring COPD biomarkers.
BackgroundThis study investigated the effects of Baohe pill decoction on the diversity and community composition of lactase-producing bacteria in the intestinal contents of mice with diarrhea induced by high-fat and high-protein diet, which provided an experimental basis for the study on the therapeutic mechanism of Baohe pill decoction.Materials and methodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP), DisGeNET, UniProt, National Center for Biotechnology Information (NCBI), and GeneCards databases were used to collect the potential targets with active ingredients of Baohe pill decoction, diarrhea, and lactase, and then construct correlation networks. Fifteen Kunming mice were randomly divided into the control group (CN), natural recovery group (NR), and Baohe pill decoction treatment group (BHP), with five mice in each group. After constructing a mouse diarrhea model by HFHPD induction, BHP was gavaged with Baohe pill decoction, and the other groups were gavaged with distilled water of equal. The intestinal contents were collected from ileal to jejunal and analyzed using metagenomic sequencing to characterize the intestinal content of lactase-producing bacteria in mice.ResultsThe core active ingredients related to diarrhea in Baohe pill decoction were quercetin, luteolin, kaempferol, forsythin, and wogonin. And there was no intersection between the potential targets with the active ingredient of Baohe pill, lactase, and diarrhea. After the intervention of Baohe pill decoction, the Observed species, Chao1 index, and Operational Taxonomic Units (OTU) number increased in BHP (P > 0.05), while the Pielous evenness and Shannon index decreased (P > 0.05). In Beta diversity, the community structure of the NR was significantly different from CN and BHP (P < 0.05), and the community structure of the CN was not significant difference from BHP (P > 0.05). Compared to NR, the relative abundance of Bifidobacterium and Amycolatopsis increased, while the relative abundance of Lachnoclostridium, Sinorhizobium, Cedecea, and Escherichia decreased in BHP, but none of the significant differences (P > 0.05).ConclusionThe therapeutic effect of Baohe pill decoction on diarrhea induced by HFHPD does not appear to involve the body’s lactase gene targets directly, but is associated with the change of the construction of lactase-producing bacterial communities.
Kunio Fujiwara, Yutaro Yamamoto, Tetsuya Saita
et al.
Abstract Among any drugs, no comparative pharmacological study on how prodrug and its active metabolite behave in animal bodies is available. Immunohistochemistry (IHCs) using newly prepared two monoclonal antibodies, AOS‐96 and AOC‐160, monospecific for oseltamivir (OS) and its metabolite oseltamivir carboxylate (OC) were developed, simultaneously detecting the uptake or excretion of OS and OC in the intestine, liver, and kidney of rats to which OS was orally administered. In the intestine, IHC for OS revealed OS highly distributed to the absorptive epithelia with heavily stained cytoplasmic small granules (CSGs). IHC for OC showed that OC also distributed highly in the epithelia, but without CSGs, suggesting that OS was partly converted to OC in the cells. In the liver, OS distributed in the hepatocytes and on their bile capillaries, as well as on the lumina from the bile capillaries to the interlobular bile ducts. OC distributed in the whole cell of the hepatocytes, but without CSGs nor on any lumina through the interlobular bile ducts. In the kidney, a few levels of OS distributed in the cytoplasm of almost all the renal tubule cells, but they contained numerous CSGs. In contrast, OC distributed highly in the proximal tubules, but very slightly in the lower renal tubules of the nephrons. Thus, it was concluded that the two drugs behave in completely different ways in rat bodies. This paper also discusses a possibility of the correlation of OS or OC levels in tissue cells with their known transporters.
Ibrahim Hassan, Wan Norhamidah Wan Ibrahim, Ferdaus Mohamat Yusuf
et al.
Background. Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed. Methods. The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC). Results. The result shows activities with high significant differences at P<0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method. Conclusion. The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.