Pea Starch-Lauric Acid Complex Alleviates Dextran Sulfate Sodium-Induced Colitis in C57BL/6J Mice.

The previous documentation has shown the role of resistant starch in promoting intestinal health, while the effect of starch-lipid complex (RS5) on colitis remains unclear. This study aimed to investigate the effect and potential mechanism of RS5 in colitis. We prepared RS5 complexes by combining pea starch with lauric acid. Mice with dextran sulfate sodium-induced colitis were treated with either RS5 (3.25 g/kg) or normal saline (10 mL/kg) for seven days, and the effects of pea starch-lauric acid complex on mice were observed. The RS5 treatment significantly attenuated weight loss, splenomegaly, colon shortening, and pathological damage in mice with colitis. Compare with the DSS group, cytokines levels, such as tumor necrosis factor-α and interleukin-6 in both serum and colon tissue was significantly decreased in RS5 treatment group, while the gene expression of interleukin-10 and the expression of mucin 2, zonula occludens-1, Occludin, and claudin-1 in the colon was significantly upregulated in RS5 treatment group. In addition, RS5 treatment altered the gut microbiota structure of colitis mice by increasing the abundance of Bacteroides and decreasing Turicibacter, Oscillospira, Odoribacter, and Akkermansia. The dietary composition could be exploited to manage colitis by attenuating inflammation, restoring the intestinal barrier, and regulating gut microbiota.

Emission spectral non-Markovianity in qubit-cavity systems in the ultrastrong coupling regime.

We study the emission spectra of the dissipative Rabi and Jaynes-Cummings models in the non-Markovian and ultrastrong coupling regimes. We have derived a polaron-transformed Nakajima-Zwanzig master equation (PTNZE) to calculate the emission spectra, which eliminates the well-known limitations of the Markovian approximation and the standard second-order perturbation. Using the time-dependent variational approach with the multiple Davydov ansatz as a benchmark, the PTNZE is found to yield accurate emission spectra in certain ultrastrong coupling regimes where the standard second-order Nakajima-Zwanzig master equation breaks down. It is shown that the emission spectra of the dissipative Rabi and Jaynes-Cummings models are, in general, asymmetric under various initial conditions. Direct comparisons of spectra for the two models illustrate the essential role of the qubit-cavity counter-rotating term and the spectral features under different qubit-cavity coupling strengths and system initial conditions.

Effect of epigallocatechin gallate on the fermentative and physicochemical properties of fermented milk.

Yogurt, a traditional fermented dairy product, is made with a starter that contains Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. The aim of this study was to investigate the effects of different concentrations of epigallocatechin gallate (EGCG; 0, 0.5, 1.0, 3.0, and 5.0 mg/mL) on the growth, metabolism, and acid production of lactic acid bacteria, as well as the texture, stability, and antioxidant activity of fermented milk (yogurt). The results showed that a low concentration of EGCG had no significant effect on the acid production capacity of the starter or on the water-holding capacity of the yogurt but did increase its viscosity. A high concentration (5.0 mg/mL) of EGCG delayed the acid production rate of the starter and decreased the water-holding capacity, but significantly increased the antioxidant activity of yogurt. The addition of EGCG significantly increased the hardness of yogurt. Therefore, EGCG can improve the texture of fermented milk and enhance its antioxidant activity and stability, thus improving the overall quality of yogurt.

Machine learning based prediction for China's municipal solid waste under the shared socioeconomic pathways.

Reliable forecast of municipal solid waste (MSW) generation is crucial for sustainable and efficient waste management. Big data analysis is a novel method to forecast MSW more accurately. Thus, this study employs five kinds of supervised machine learning approaches including linear regression, polynomial regression, support vector machine, random forest, and extreme gradient boosting (XGBoost) to examine their forecast performances. China's MSW generation from 2020 to 2060 under five shared socioeconomic pathways (SSPs) is further predicted and the mechanisms between MSW generation and socioeconomic features are explored. Results show that population and GDP are two dominant indicators in MSW prediction, and XGBoost model is proved to be effective in MSW forecast. MSW generation of China in 2060 is estimated to be 464-688 megatons under different SSPs scenarios, about four to six times of that in 2000. SSP3 that has the most population, least GDP and the highest climate change challenges is the only scenario showing a potential of MSW peak during the study period. The key for MSW increase is mainly the increase of per capita MSW caused by GDP. Finally, several policy recommendations are raised to reduce the overall MSW generation.

Nanoaperture fabrication in ultra-smooth single-grain gold films with helium ion beam lithography.

We demonstrate a simple three-step gold thin-film sample preparation process to enhance the morphology and lithographic precision using helium ion based direct-writing. The procedure includes metal deposition, heat treatment and template stripping, which produce smooth monocrystalline gold grains with sizes up to 500 nm and an average surface roughness of 0.267 nm. By using a helium ion microscope, we can fabricate structures with feature sizes less than 20 nm in a 100 nm thick gold film with high-quality sidewalls. We demonstrate the efficacy of this technique by producing high-quality double nanohole (DNH) nanoapertures for single nanoparticle trapping in a single grain of 100 nm thick gold. This procedure can be applied to a wide range of antenna geometries and features that need to be fabricated producing optical and or electronic devices.

Optimization of metallic nanoapertures at short-wave infrared wavelengths for self-induced back-action trapping.

This paper presents simulation results for double nanohole and inverted bowtie nanoapertures optimized to resonate in the short-wave infrared regime (1050 nm and 1550 nm). These geometries have shown great promise for trapping nanoparticles with applications in optical engineering, physics, and biology. Using a finite element analysis tool, we found that the outline length for inverted bowtie nanoapertures in a 100 nm thick gold film with a 20 nm gap dimension having an optimized transmission resonance for 1050 nm and 1550 nm optical wavelengths is 106.5 nm and 188.5 nm, respectively. With the same gap size, the radii of the circles for the double nanohole nanoapertures are 72 nm and 128 nm. The near-field enhancements of the two structures are almost the same, while the double nanohole geometries have a 20% larger full width at half-maximum than the inverted bowtie. Next, by studying the effect of changing the inner radii of the inverted bowtie corners, we found that the difference between 2 nm and 6 nm corner radii can blue-shift the optical resonance by up to 45 nm. As a result of not having any inner corners, the double nanohole structure requires less precise fabrication and therefore could potentially have a higher successful yield of nanoapertures during the manufacturing process. Lastly, we will show experimental results that confirm the optical resonance of the nanoapertures at 1550 nm. These results will enable better performance and signal-to-noise ratio in nanoaperture trapping for the short-wave infrared wavelength regime.

Cyclin Y Modulates the Proliferation, Invasion, and Metastasis of Hepatocellular Carcinoma Cells.

BACKGROUND Cyclin Y (CCNY) is a member of the cyclin family of proteins that regulate the cell cycle. The aims of this study were to compare the expression of CCNY in normal liver and human hepatocellular carcinoma (HCC), in normal and HCC cell lines, and in mouse HCC tumor xenografts. MATERIAL AND METHODS Tumor tissues from 55 patients diagnosed with HCC were studied for CCNY expression. Human HCC cell lines, SK-Hep1, HepG2, HEP3B, HuH7 and L02 were studied using the MTT cell proliferation assay, cell apoptosis, transwell and wound healing assays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to measure CCNY expression. Indirect immunofluorescence was used to assess cell apoptosis. In vivo xenograft mouse model was constructed and examined histologically. RESULTS Expression of CCNY in human HCC tumor tissues was significantly increased when compared with adjacent normal liver (all P<0.05). HCC cells grown in vitro showed significantly increased expression of CCNY, cell proliferation, and migration, and a reduced rate of apoptosis, compared with cells with CCNY knockdown (siRNA) (all P<0.05). In the xenograft mouse model, tumor volume and weight in the CCNY overexpression group were significantly increased, compared with CCNY knockdown (siRNA) group (all P<0.05). CONCLUSIONS In tissue samples of human HCC, and human HCC cell lines, increased expression of CCNY was significantly associated with cell proliferation and migration. Further studies are recommended to evaluate the role of CCNY as a potential diagnostic biomarker or target for treatment in human HCC.

All-fiber mode converter based on long-period fiber gratings written in few-mode fiber.

We investigated an all-fiber mode converter based on long-period fiber gratings (LPFGs) written in the few-mode fiber. Mode conversion between the fundamental core mode and different higher-order core modes (LP11, LP21, and LP02 modes) can be realized via a single LPFG with an efficiency of 99% at the resonance wavelength. Moreover, optimized mode conversion between the LP01 and LP21 modes can be realized by cascading two LPFGs with different grating pitches. The maximum conversion efficiency is estimated to be ∼99.5% at 1553 nm. The orbital angular momentum states with different topological charges (±1,±2) are demonstrated experimentally. The all-fiber LPFG mode converters could have promising applications in the mode-division multiplexing optical communications.

Mode converter based on the long-period fiber gratings written in the two-mode fiber.

We demonstrate the fabrication of long-period fiber gratings (LPFGs) written in the two-mode fiber (TMF) by CO2 laser. Both uniform and tilted LPFGs were fabricated to provide the light coupling between LP01 mode and LP11 mode with a coupling efficiency of more than 99%. The writing efficiency and the bandwidth of the LPFG mode converter can be adjusted by changing the tilt angle of the tilted TMF-LPFGs. The torsion sensitivity of conventional and tilted LPFG mode converters were measured to be 0.37 nm/(rad/m) and 0.50 nm/(rad/m), respectively. Two orthogonal vector modes (the HEeven 21and HEodd 21 modes) and corresponding orbital angular momentum state were successfully obtained at the resonance wavelength. The proposed LPFG mode converter could be used as not only a high efficiency wavelength tunable mode converter in the mode division multiplexing system but also a high sensitive torsion sensor in the field of optical sensing.

Comparing Mycobacterium tuberculosis genomes using genome topology networks.

BACKGROUND: Over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. Several findings have revealed that genomic structural variations (SVs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by SVs may extend our knowledge of the relationships between SVs and phenotypes in microbes, especially in pathogenic bacteria. RESULTS: In this work, we introduce a 'Genome Topology Network' (GTN) method based on gene homology and gene locations to analyze genomic SVs and perform phylogenetic analysis. Furthermore, the concept of 'unfixed ortholog' has been proposed, whose members are affected by SVs in genome topology among close species. To improve the precision of 'unfixed ortholog' recognition, a strategy to detect annotation differences and complete gene annotation was applied. To assess the GTN method, a set of thirteen complete M. tuberculosis genomes was analyzed as a case study. GTNs with two different gene homology-assigning methods were built, the Clusters of Orthologous Groups (COG) method and the orthoMCL clustering method, and two phylogenetic trees were constructed accordingly, which may provide additional insights into whole genome-based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most members were related to immunogenicity and drug resistance, such as PPE-repeat proteins (COG5651) and transcriptional regulator TetR gene family members (COG1309). CONCLUSIONS: The GTN method has been implemented in PERL and released on our website. The tool can be downloaded from http://homepage.fudan.edu.cn/zhouyan/gtn/ , and allows re-annotating the 'lost' genes among closely related genomes, analyzing genes affected by SVs, and performing phylogenetic analysis. With this tool, many immunogenic-related and drug resistance-related genes were found to be affected by SVs in M. tuberculosis genomes. We believe that the GTN method will be suitable for the exploration of genomic SVs in connection with biological features of bacterial strains, and that GTN-based phylogenetic analysis will provide additional insights into whole genome-based phylogenetic analysis.

Multi-Objective Self-Adaptive Particle Swarm Optimization for Large-Scale Feature Selection in Classification.

Feature selection (FS) is recognized for its role in enhancing the performance of learning algorithms, especially for high-dimensional datasets. In recent times, FS has been framed as a multi-objective optimization problem, leading to the application of various multi-objective evolutionary algorithms (MOEAs) to address it. However, the solution space expands exponentially with the dataset's dimensionality. Simultaneously, the extensive search space often results in numerous local optimal solutions due to a large proportion of unrelated and redundant features [H. Adeli and H. S. Park, Fully automated design of super-high-rise building structures by a hybrid ai model on a massively parallel machine, AI Mag. 17 (1996) 87-93]. Consequently, existing MOEAs struggle with local optima stagnation, particularly in large-scale multi-objective FS problems (LSMOFSPs). Different LSMOFSPs generally exhibit unique characteristics, yet most existing MOEAs rely on a single candidate solution generation strategy (CSGS), which may be less efficient for diverse LSMOFSPs [H. S. Park and H. Adeli, Distributed neural dynamics algorithms for optimization of large steel structures, J. Struct. Eng. ASCE 123 (1997) 880-888; M. Aldwaik and H. Adeli, Advances in optimization of highrise building structures, Struct. Multidiscip. Optim. 50 (2014) 899-919; E. G. González, J. R. Villar, Q. Tan, J. Sedano and C. Chira, An efficient multi-robot path planning solution using a* and coevolutionary algorithms, Integr. Comput. Aided Eng. 30 (2022) 41-52]. Moreover, selecting an appropriate MOEA and determining its corresponding parameter values for a specified LSMOFSP is time-consuming. To address these challenges, a multi-objective self-adaptive particle swarm optimization (MOSaPSO) algorithm is proposed, combined with a rapid nondominated sorting approach. MOSaPSO employs a self-adaptive mechanism, along with five modified efficient CSGSs, to generate new solutions. Experiments were conducted on ten datasets, and the results demonstrate that the number of features is effectively reduced by MOSaPSO while lowering the classification error rate. Furthermore, superior performance is observed in comparison to its counterparts on both the training and test sets, with advantages becoming increasingly evident as the dimensionality increases.

miR-92a-3p regulates ethanol-induced apoptosis in H9c2 cardiomyocytes.

The role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes remains unclear. In this study, we explored the role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes and identified its target genes and signaling pathways. H9c2 cells were cultured with or without 100 mM ethanol for 24 h. The differential expression of miR-92a-3p was verified in H9c2 cells through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To manipulate the expression of miR-92a-3p, both a mimic and an inhibitor were transfected into H9c2 cells. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and apoptosis-related antibodies were used for apoptosis detection through flow cytometry and Western blotting, respectively. Target genes were verified through RT-qPCR, Western blotting, and double luciferase reporter gene assays. miR-92a-3p was significantly overexpressed in ethanol-stimulated H9c2 cardiomyocytes (P < 0.001). After ethanol stimulation, H9c2 myocardial cells exhibited increased apoptosis. The apoptosis rate was higher in the miR-92a-3p mimic group than in the control group. However, the apoptosis rate was lower in the miR-92a-3p inhibitor group than in the control group, indicating that miR-92a-3p promotes the ethanol-induced apoptosis of H9c2 myocardial cells. RT-qPCR and Western blotting revealed that the miR-92a-3p mimic and inhibitor significantly regulated the mRNA and protein expression levels of mitogen- and stress-activated protein kinase 2 and cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2), suggesting that miR-92a-3p promotes the apoptosis of H9c2 cardiomyocytes by inhibiting the MSK2/CREB/Bcl-2 pathway. Therefore, the apoptosis of H9c2 cardiomyocytes increases after ethanol stimulation, and miR-92a-3p can directly target MSK2 and CREB3L2, thereby promoting the ethanol-induced apoptosis of H9c2 myocardial cells.

Alcoholic Liver Disease in China: A Disease Influenced by Complex Social Factors That Should Not Be Neglected.

Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.

Low-level Nd:YAG laser inhibiting inflammation and oxidative stress in human gingival fibroblasts via AMPK/SIRT3 axis.

OBJECTIVE: Photobiomodulation is extensively employed in the management of chronic inflammatory diseases such as periodontitis because of its anti-inflammatory and antioxidant effects. This study used low-level Nd:YAG laser to investigate the mechanism of photobiomodulation as well as the role of adenosine monophosphate-activated protein kinase (AMPK) and Sirtuins (SIRT) 3 in it, providing new clues for the treatment of periodontitis. METHODS: Human gingival fibroblasts (HGFs) were extracted from gingiva and stimulated with LPS. The suitable parameters of Nd:YAG laser were chosen for subsequent experiments by detecting cell viability. We assessed the level of inflammation and oxidative stress as well as AMPK and SIRT3. The mechanism for AMPK targeting SIRT3 modulating the anti-inflammatory and antioxidant effects of photobiomodulation was explored by the AMPK inhibitor (Compound C) test, cell transfection, western blot, and immunofluorescence. RESULTS: HGFs were isolated and identified, followed by the identification of optimal Nd:YAG laser parameters (60 mJ, 15 Hz, 10s) for subsequent experimentation. With this laser, inflammatory factors (IL-6, TNF-α, COX2, and iNOS) decreased as well as the phosphorylation and nuclear translocation of NFκB-P65. SOD2 was up-regulated but reactive oxygen species (ROS) was down-regulated. The laser treatment exhibited enhancements in AMPK phosphorylation and SIRT3 expression. The above effects could all be reversed by Compound C. Silencing AMPK or SIRT3 by siRNA, the down-regulation of COX2, iNOS, and ROS by laser was inhibited. SIRT3 was down-regulated when the AMPK was silenced. CONCLUSION: Low-level Nd:YAG laser activated AMPK-SIRT3 signaling pathway, facilitating the anti-inflammatory and antioxidative activity.

Depletion of PHF14, a novel histone-binding protein gene, causes neonatal lethality in mice due to respiratory failure.

The plant homeodomain (PHD) finger is identified in many chromatin-binding proteins, and functions as a 'reader' that recognizes specific epigenetic marks on histone tails, bridging transcription factors and their associated complexes to chromatin, and regulating gene expression. PHD finger-containing proteins perform many biological functions and are involved in many human diseases including cancer. PHF14 is predicted to code for a protein with multiple PHD fingers. However, its function is unidentified. The aim of this study is to characterize PHF14 and investigate its biological significance by employing multiple approaches including mouse gene-targeting knockout, and molecular cloning and characterization. Three transcripts of PHF14 in human cell lines were identified by reverse transcriptase polymerase chain reaction. Two isoforms of PHF14 (PHF14α and PHF14ß) were cloned in this study. It was found that PHF14 was ubiquitously expressed in mouse tissues and human cell lines. PHF14α, the major isoform of PHF14, was localized in the nucleus and also bound to chromatin during cell division. Interestingly, co-immunoprecipitation results suggested that PHF14α bound to histones via its PHD fingers. Strikingly, gene-targeting knockout of PHF14 in mice resulted in a neonatal lethality due to respiratory failure. Pathological analysis revealed severe disorders of tissue and cell structures in multiple organs, particularly in the lungs. These results indicated that PHF14 might be an epigenetic regulator and play an important role in the development of multiple organs in mouse.

Ni3S2/MxSy-NiCo LDH (M = Cu, Fe, V, Ce, Bi) heterostructure nanosheet arrays on Ni foam as high-efficiency electrocatalyst for electrocatalytic overall water splitting and urea splitting.

Here, we synthesized a series of Ni3S2/MxSy-NiCo LDH materials (M = Cu, Fe, V, Ce, and Bi) by a two-step hydrothermal method for the first time, which display excellent oxygen evolution reaction (OER) and urea oxidation reaction (UOR) properties. M (M = Cu, Fe, V, Ce, and Bi) ions were firstly doped into NiCo LDH to change the original electronic structure and enhance the activity of the LDH. Then, Ni3S2 and MxSy were introduced by sulfurization of the Ni support and doping cations, and the combination of Ni3S2, MxSy and NiCo-LDH improved the electron transfer rate and activity of the original material. With Ni3S2/Bi2S3-NiCo LDH/NF as anode and Ni3S2/CuS-NiCo LDH as cathode, an electrolytic cell can reach 10 mA cm-2 at 1.622 V with outstanding durability for overall water splitting. In addition, with Ni3S2/Bi2S3-NiCo LDH/NF as both electrodes, it can reach 10 mA cm-2 at 1.56 V with outstanding durability for overall urea splitting, which is better than that of the overall water splitting. Density functional theory (DFT) calculation shows that the superior electrocatalytic activity can be explained by the water adsorption energy being optimized and enhanced conductivity. This study provides a new idea for improving the catalytic activity and stability of non-noble metals instead of noble metals.

In situ construction of WNiM-WNi LDH (M = Se, S, or P) with heterostructure as highly efficient electrocatalyst for overall water splitting and urea oxidation reaction.

Electrochemical water splitting as an important means of obtaining high purity hydrogen fuel has attracted great interest. In this study, the structural engineering of complex WNiM-WNi LDH (M = Se, S, or P) was firstly developed by in situ growth on Ni foam for use in overall water splitting and the urea oxidation reaction. These WNiM-WNi LDH (M = Se, S, or P) catalysts exhibit outstanding electrocatalytic performance in the hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and urea oxidation reaction (UOR), respectively. An overpotential of only 64 mV of OER is required for WNiS-WNi LDH and 126 mV of HER is required for WNiP-WNi LDH to achieve 10 mA cm-2. The WNiSe-WNi LDH materials display a particularly outstanding performance for UOR, requiring a potential of 1.25 V to drive 10 mA cm-2. Moreover, the optimized WNiS-WNi LDH as an anode and WNiP-WNi LDH as a cathode can achieve 10 mA cm-2 at a low cell voltage of 1.45 V in 1 M KOH solution for overall water splitting. The density functional theory calculations show that the introduction of the NiP2 and WP material greatly reduces the Gibbs free energy of the hydrogen adsorption of the material.

Exergy analysis of natural resources embodied in China's interregional trade and its implication for regional imbalance.

Large-scaled interregional trade is based upon massive exchanges of natural resources, leading to more environmental emissions and economic imbalance. China is the largest trade country in the world and has to face such challenges since different Chinese provinces are in different development stages with different resource endowments. By using the latest multi-regional input-output (MRIO) tables and exergy accounting, this study aims to investigate natural resources and added values embodied in interregional trade in China for years of 2012, 2015, and 2017. Regional environmental inequality (REI) index and logarithmic mean Divisia index (LMDI) were applied to measure the imbalance states and uncover corresponding driving factors. Results show that the total trade volumes in the middle Yellow River and eastern coastal regions were generally higher than those in other regions, together accounting for 41.50 ~ 41.78% of the total trade volume during the study period. The major flows of embodied natural resources shifted from the middle Yellow River region to western coastal, eastern coastal, and southern coastal regions. The northern coastal and eastern coastal regions were the major exporters of embodied added value. Less developed regions had higher REI values, indicating more environmental and economic losses than developed regions. Natural resources intensity was the major impact factor on the trade imbalances in most provinces. This study provides valuable insights for alleviating trade imbalance and promoting sustainable natural resources management based on cross-regional collaboration.

Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages.

Objective: Emerging studies have explained the crucial role of non-coding RNA (lncRNA) in various pathological progressions. The study was designed to examine the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miRNA-124 in the differentiation of osteoclasts, to provide new clues or evidences for the pathogenesis of periodontitis. Methods: We constructed an osteoblast-osteoclast Transwell co-culture system and osteoblast-derived exosomes (OB-exo) intervention model. We assessed the osteoclastogenesis as well as the level of lncRNA-MALAT1 and miRNA-124. The mechanism for lncRNA MALAT1 targeting miR-124 modulating the differentiation of osteoclasts was investigated by cell transfection, quantitative real-time reverse transcription PCR (RT-qPCR), Western blot, and Dual-Luciferase reporter assays. Results: Osteoblast-derived exosomes were isolated and identified. Co-culture and OB-exo intervention can promote osteoclastogenesis, also significantly up-regulate the expression of MALAT1, while the level of miR-124 is the opposite. Transfection of cells with small interfering RNA (si-MALAT1) and miR-124 mimic decreased the formation of TRAP+ osteoclasts and inhibited the expression of NFATc1. However, the effect was reversed when transfected with miR-124 inhibitor and si-MALAT1. The Dual-Luciferase reporter assay confirmed the binding sites between MALAT1 and miR-124, and miR-124 and NFATc1. Conclusion: LncRNA MALAT1 functioned as an endogenous sponge by competing for miR-124 binding to regulate NFATc1 expression, accelerating the progression of osteoclastogenesis.

Osteoclast-Derived Exosomal miR-5134-5p Interferes with Alveolar Bone Homeostasis by Targeting the JAK2/STAT3 Axis.

Background: In chronic periodontitis, exosomes transport various informative substances between osteoclasts and osteoblasts in alveolar bone. Herein, we aimed to investigate the effect of exosomal micro-ribonucleic acid (miRNA/miR)-5134-5p derived from osteoclasts on osteoblastic proliferation and differentiation and the development of periodontitis in vivo and in vitro. Methods: The effects of OC-Exos on the proliferation and differentiation of osteoblasts were identified by Real-time quantitative reverse polymerase chain reaction (qRT-PCR), Western blot(WB), alkaline phosphatase(ALP) staining, etc. Exosomal miRNA expression was analyzed by sequencing. The sites of miRNA action were predicted through TargetScan and tested by double luciferase assay. After transfecting miR-5134-5p mimic/inhibitor into osteoblasts, we measured the proliferation and differentiation of osteoblasts by ALP staining and WB, etc. Furthermore, OC-Exos were injected into the gingival sulcus at the ligation site. Inflammation was observed by Hematoxylin-eosin (H&E) staining, the expression of inflammatory factors were detected by qRT-PCR, the resorption of alveolar bone was observed by Micro CT. Results: Osteoblastic proliferation and differentiation were negatively regulated by OC-Exos in vitro. miRNA sequencing analysis revealed that miR-5134-5p expression was significantly elevated in OC-Exos, which also increased in osteoblasts following OC-Exo intervention. The dual-luciferase assay revealed that miR-5134-5p and Janus kinase 2 (JAK2) had binding sites. miR-5134-5p-mimics could upregulate miR-5134-5p expression in osteoblasts while downregulating Runt-related transcription factor 2(Runx2), phosphorylated-JAK2 (p-JAK2), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) expression and inhibited osteogenic differentiation. However, miR-5134-5p-inhibitor had the opposite effect. In vivo, the OC-Exo group demonstrated morphological disruption of periodontal tissue, massive inflammatory cell infiltration, upregulation of inflammatory factors mRNA expression, a significant decrease in BV/TV, and an increase in the cementoenamel junction and alveolar bone crest distance. Conclusion: Osteoclast-derived exosomal miR-5134-5p inhibits osteoblastic proliferation and differentiation via the JAK2/STAT3 pathway. OC-Exos exacerbate periodontal tissue inflammation and accelerate alveolar bone resorption in mice with experimental periodontitis.