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A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.

Background Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. Methods We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. Results Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. Conclusions Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

Positive and negative pressures determine the performance of pneumatic precision metering device for rapeseed. In order to investigate the relationship between positive and negative pressures of nozzles, fluid models of chamber were developed to simulate the airflow, and the k-ε turbulence model was conducted to capture the pressure and velocity of nozzles. Through these efforts linear models were achieved. Meanwhile, the three-factor factorial split-split experiment was designed with negative pressure, positive pressure and the rotating speeds varying from -1 000 to -4 500 Pa, 50 to 250 Pa and 10 to 45 r/min, respectively. The mathematical models were developed through employing the stepwise regression method. The sequence of influential factors on the quality of feed index was positive pressure, negative pressure and rotating speed. To obtain the match regulation of negative and positive pressures with \"good\" performance, the ratio coefficient K of negative and positive pressures was introduced to build mathematical models. Models relating ratio coefficient K with positive pressure were fitted in different rotating speeds. The results showed that the ratio coefficient was matched Γ∈[f^sub 1^(x), f^sub 2^(x)] from the fitting equations with the rotating speed of 10 - 30 r/min; while the rotating speed has greater influence when it was 35 - 40 r/min and the sets Λ∈[g^sub 1^(x), g^sub 2^(x)] were achieved, where x∈[100, 250]. This study could be conducted to adjust the rotating speed of the pneumatic system to optimize the ideal performance of the seeder.

Dry reforming of methane (DRM) is an attractive route to utilize CO 2 as a chemical feedstock with which to convert CH 4 into valuable syngas and simultaneously mitigate both greenhouse gases. Ni-based DRM catalysts are promising due to their high activity and low cost, but suffer from poor stability due to coke formation which has hindered their commercialization. Herein, we report that atomically dispersed Ni single atoms, stabilized by interaction with Ce-doped hydroxyapatite, are highly active and coke-resistant catalytic sites for DRM. Experimental and computational studies reveal that isolated Ni atoms are intrinsically coke-resistant due to their unique ability to only activate the first C-H bond in CH 4 , thus avoiding methane deep decomposition into carbon. This discovery offers new opportunities to develop large-scale DRM processes using earth abundant catalysts. While dry reforming of methane, the reaction of CH 4 and CO 2 to create CO and H 2 , is a promising reaction for industry, coke buildup often deactivates catalysts and limits commercialization. Here, authors report single-atom nickel on Ce-doped hydroxyapatite as a coke-resistant catalyst.

Organic heterostructures (OHSs) integrating the intrinsic heterostructure characters as well as the organic semiconductor properties have attracted intensive attention in material chemistry. However, the precise bottom-up synthesis of OHSs is still challenging owing to the general occurrence of homogeneous-nucleation and the difficult manipulation of noncovalent interactions. Herein, we present the rational synthesis of the longitudinally/horizontally-epitaxial growth of one-dimensional OHSs including triblock and core/shell nanowires with quantitatively-manipulated microstructure via a hierarchical self-assembly method by regulating the noncovalent interactions: hydrogen bond (−15.66 kcal mol −1 ) > halogen bond (−4.90 kcal mol −1 ) > π-π interaction (−0.09 kcal mol −1 ). In the facet-selective epitaxial growth strategy, the lattice-matching and the surface-interface energy balance respectively facilitate the realization of triblock and core/shell heterostructures. This hierarchical self-assembly approach opens up avenues to the fine synthesis of OHSs. We foresee application possibilities in integrated optoelectronics, such as the nanoscale multiple input/out optical logic gate with high-fidelity signal. Organic heterostructures attract attention in material chemistry but the precise bottom-up synthesis is still challenging. Herein the authors present a hierarchical self-assembly approach to synthesize one-dimensional organic heterostructures by regulating the noncovalent interactions.

ObjectiveTo identify the feasibility of using a deep convolutional neural network (DCNN) for the detection and localization of hip fractures on plain frontal pelvic radiographs (PXRs).Summary of background dataHip fracture is a leading worldwide health problem for the elderly. A missed diagnosis of hip fracture on radiography leads to a dismal prognosis. The application of a DCNN to PXRs can potentially improve the accuracy and efficiency of hip fracture diagnosis.MethodsA DCNN was pretrained using 25,505 limb radiographs between January 2012 and December 2017. It was retrained using 3605 PXRs between August 2008 and December 2016. The accuracy, sensitivity, false-negative rate, and area under the receiver operating characteristic curve (AUC) were evaluated on 100 independent PXRs acquired during 2017. The authors also used the visualization algorithm gradient-weighted class activation mapping (Grad-CAM) to confirm the validity of the model.ResultsThe algorithm achieved an accuracy of 91%, a sensitivity of 98%, a false-negative rate of 2%, and an AUC of 0.98 for identifying hip fractures. The visualization algorithm showed an accuracy of 95.9% for lesion identification.ConclusionsA DCNN not only detected hip fractures on PXRs with a low false-negative rate but also had high accuracy for localizing fracture lesions. The DCNN might be an efficient and economical model to help clinicians make a diagnosis without interrupting the current clinical pathway.Key Points• Automated detection of hip fractures on frontal pelvic radiographs may facilitate emergent screening and evaluation efforts for primary physicians.• Good visualization of the fracture site by Grad-CAM enables the rapid integration of this tool into the current medical system.• The feasibility and efficiency of utilizing a deep neural network have been confirmed for the screening of hip fractures.

Protein nanopores offer an inexpensive, label-free method of analysing single oligonucleotides. The sensitivity of the approach is largely determined by the characteristics of the pore-forming protein employed, and typically relies on nanopores that have been chemically modified or incorporate molecular motors. Effective, high-resolution discrimination of oligonucleotides using wild-type biological nanopores remains difficult to achieve. Here, we show that a wild-type aerolysin nanopore can resolve individual short oligonucleotides that are 2 to 10 bases long. The sensing capabilities are attributed to the geometry of aerolysin and the electrostatic interactions between the nanopore and the oligonucleotides. We also show that the wild-type aerolysin nanopores can distinguish individual oligonucleotides from mixtures and can monitor the stepwise cleavage of oligonucleotides by exonuclease I. A wild-type aerolysin nanopore can resolve individual short oligonucleotides that are 2 to 10 bases long, and can monitor the stepwise cleavage of oligonucleotides by exonuclease I.

Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease. Synopsis Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis. COL has been identified as a novel efferocytosis enhancer that ameliorates mouse colitis. COL binds to and biasedly activates FPR2, leading to enhanced efferocytosis in macrophages. FPR2 emerges as a promising therapeutic target for the treatment of inflammatory diseases through modulating LC3‐associated efferocytosis in macrophages. Graphical Abstract Enhancement of efferocytosis has been regarded as an emerging strategy for inflammatory diseases, while pharmacological approaches to modulate efferocytosis are poorly defined. Our study identified a natural compound, columbamine (COL), that can activate LC3‐associated efferocytosis and attenuate DSS‐induced colitis by biasedly targeting FPR2 on macrophages. This study provides a novel therapeutic strategy for inflammatory diseases, including colitis, via enhancing FPR2‐mediated efferocytosis.

Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing new therapeutic strategies. Oncolytic viruses have emerged as a promising option. Oncolytic viruses selectively replicate within tumor cells, destroying them and stimulating the immune system for an enhanced anticancer response. Among Oncolytic viruses investigated for recurrent gliomas, oncolytic herpes simplex virus and oncolytic adenovirus show notable potential. Genetic modifications play a crucial role in optimizing their therapeutic efficacy. Different generations of replicative conditioned oncolytic human adenovirus and oncolytic HSV have been developed, incorporating specific modifications to enhance tumor selectivity, replication efficiency, and immune activation. This review article summarizes these genetic modifications, offering insights into the underlying mechanisms of Oncolytic viruses’ therapy. It also aims to identify strategies for further enhancing the therapeutic benefits of Oncolytic viruses. However, it is important to acknowledge that additional research and clinical trials are necessary to establish the safety, efficacy, and optimal utilization of Oncolytic viruses in treating recurrent glioblastoma.

Aerolysin nanopores are being used to discriminate between oligonucleotides of different length, composition and concentration. This protocol describes the procedures for aerolysin nanopore formation in lipid bilayers, quality checks and data analysis. Nanopore techniques offer the possibility to study biomolecules at the single-molecule level in a low-cost, label-free and high-throughput manner. By analyzing the level, duration and frequency of ionic current blockades, information regarding the structural conformation, mass, length and concentration of single molecules can be obtained in physiological conditions. Aerolysin monomers assemble into small pores that provide a confined space for effective electrochemical control of a single molecule interacting with the pore, which significantly improves the temporal resolution of this technique. In comparison with other reported protein nanopores, aerolysin maintains its functional stability in a wide range of pH conditions, which allows for the direct discrimination of oligonucleotides between 2 and 10 nt in length and the monitoring of the stepwise cleavage of oligonucleotides by exonuclease I (Exo I) in real time. This protocol describes the process of activating proaerolysin using immobilized trypsin to obtain the aerolysin monomer, the construction of a lipid membrane and the insertion of an individual aerolysin nanopore into this membrane. A step-by-step description is provided of how to perform single-oligonucleotide analyses and how to process the acquired data. The total time required for this protocol is ∼3 d.