Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.

In-situ magnetite deposited wood composites with extensive electromagnetic interference shielding performance.

Wood is an insulator material, using its porous structure to endow it with efficient microwave absorption and broaden its application range is still a major challenge. Here, wood-based Fe3O4 composites with excellent microwave absorption properties and high mechanical strength were prepared by alkaline sulfite method, in-situ co-precipitation method and compression densification method. The results showed that the magnetic Fe3O4 was densely deposited in the wood cells, and the prepared wood-based microwave absorption composites had both high electrical conductivity, magnetic loss, excellent impedance matching performance and attenuation performance, as well as effective microwave absorption properties. In the frequency range of 2-18 GHz, the minimum reflection loss value was -25.32 dB. At the same time, it had high mechanical properties. Compared with the untreated wood, its modulus of elasticity (MOE) in bending increased by 98.77%, and modulus of rapture (MOR) in bending improved by 67.9%. The developed wood-based microwave absorption composite is expected to be used in electromagnetic shielding fields such as anti-radiation and anti-interference.

The active ingredient (DSH-20) of Salvia miltiorrhiza flower reduces oxidative damage and apoptosis in cardiomyocytes by regulating miR-1.

BACKGROUND: DSH-20, the active ingredient of Salvia miltiorrhiza flower extract, is used to treat cardiovascular diseases. However, its mechanism of action remains unclear. Herein, we investigated the intervention of DSH-20 in H2O2-induced oxidative damage and apoptosis in cardiomyocytes. METHODS AND RESULTS: H2O2 was used to induce oxidative damage and apoptosis in H9c2 cardiomyocytes. Based on concentration gradient studies, we found that 62.5 µg/mL DSH-20 significantly reduced reactive oxygen species and lactate dehydrogenase levels and increased superoxide dismutase levels. DSH-20 also alleviated the apoptosis rate, the changes in mRNA of apoptosis-related genes (Bcl-2, BAX, and Caspase-3) and miR-1 expression. Moreover, transfection of miR-1 mimics aggravated oxidative damage and apoptosis, whereas DSH-20 alleviated these effects. CONCLUSIONS: DSH-20 reduced H2O2-induced oxidative damage and apoptosis in H9c2 cardiomyocytes likely by downregulating miR-1 expression.

miR-126 regulates angiogenesis in myocardial ischemia by targeting HIF-1α.

Promoting angiogenesis by targeting various angiogenic regulators has emerged as a new treatment strategy for myocardial ischemia (MI). MicroRNA-126 (miR-126) has been identified as the main regulator of compensatory angiogenesis; however, its role in MI is unclear. A rat MI model and an EA. hy926 endothelial cell hypoxia model were constructed and it was found that miR-126 was highly expressed in both models. The knockdown of HIF-1α expression in EA. hy926 cells in turn downregulated VEGF and CD34 expression and consequently inhibited angiogenesis. MiR-126 inhibitor inhibited EA. hy926 cell migration and tube formation as well as downregulated VEGF and CD34 expression, and these were reversed by transfection of miR-126 mimics. Rescue tests using miR-126 and HIF-1α demonstrated that miR-126-mediated regulation of angiogenesis was dependent on HIF-1α. In summary, miR-126 regulates the occurrence and progression of angiogenesis during MI via HIF-1α and may be a potential new therapeutic target.

Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity.

Probiotics are beneficial active microorganisms that colonize the human intestines and change the composition of the flora in particular parts of the host. Recently, the use of probiotics to regulate intestinal flora to improve host immunity has received widespread attention. Recent evidence has shown that probiotics play significant roles in gut microbiota composition, which can inhibit the colonization of pathogenic bacteria in the intestine, help the host build a healthy intestinal mucosa protective layer, and enhance the host immune system. Based on the close relationship between the gut microbiota and human immunity, it has become an extremely effective way to improve human immunity by regulating the gut microbiome with probiotics. In this review, we discussed the influence of probiotics on the gut microbiota and human immunity, and the relationship between immunity, probiotics, gut microbiota, and life quality. We further emphasized the regulation of gut microflora through probiotics, thereby enhancing human immunity and improving people's lives.

Effects of One-Step Hot Oil Treatment on the Physical, Mechanical, and Surface Properties of Bamboo Scrimber.

Bamboo scrimber is a new type of bamboo-based panel that is prone to be affected by biological and service environments under outdoor conditions. In this paper, the physical and mechanical performance and the microchemical and surface properties of untreated and hot-oil-treated bamboo scrimber were analyzed to illustrate the processing mechanism of scrimber. Methyl silicone oil treatment was carried out at 120, 140, and 160 °C for 2, 4, and 6 h. The density, mechanical properties, air-dried moisture content, surface morphology, chemical structure, swelling properties, color, and contact angle of the bamboo scrimber were analyzed to evaluate the treatment effectiveness. Observation of the environmental-scanning electron microscope indicated that the glue layer of the bamboo scrimber was not significantly damaged after hot oil treatment. At low temperatures, the mechanical properties did not change significantly. Infrared-spectrum analysis showed a significant decrease in mechanical properties at higher temperatures and longer treatment time for the degradation of hemicellulose. The contact angle test and swelling properties test showed that the hot oil treatment improved the dimensional stability and reduced the wettability on the surface of the bamboo scrimber. The above analysis results show that the treatment at 140 °C for 2 h is most effective.

Identification of key microRNAs in the carotid arteries of ApoE-/- mice exposed to disturbed flow.

BACKGROUND: Atherosclerosis (AS) is one of the main causes of cardiovascular disease. AS plaques often occur in blood vessels with oscillatory blood flow and their formation can be regulated by microRNAs (miRNAs). The aim of this study is to identify the key miRNAs and molecular pathways involved in this pathological process. METHODS: In this study, gene chip data obtained from the GEO database was analyzed using the LIMMA package to find differentially expressed miRNAs (DE miRNAs) in the carotid arteries of ApoE-/- mice exposed to different blood flow rates. Predicted targets of the DE miRNAs were identified using the TargetScan, miRDB, and DIANA databases respectively, and the potential target genes (PTGs) were found by analyzing the common results of three databases. The DAVID database was used to enrich the PTGs based on gene ontology (GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG), and the STRING database was used to uncover any protein-protein interactions (PPI) of the PTGs. RESULTS: The networks of the DE miRNAs-PTGs, Pathway-PTGs-DE miRNAs, and PTGs PPI, were constructed using Cytoscape, and 11 up-regulated and 13 down-regulated DE miRNAs and 1479 PTGs were found. GO results showed that PTGs were significantly enriched in functions such as transcriptional regulation and DNA binding. KEGG results showed that PTGs were significantly enriched in inflammation-related mitogen-activated protein kinase (MAPK) and AS-related FOXO pathways. The PPI network revealed some key target genes in the PTGs. CONCLUSIONS: The analysis of key miRNAs and molecular pathways that regulate the formation of AS plaques induced by oscillatory blood flow will provide new ideas for AS treatment.

YiqiHuoxue Decoction and Its Ethanol Precipitation Show Anti-Platelet and Antithrombotic Effects by Suppressing Thromboxane B2 Formation.

BACKGROUND: YiqiHuoxue decoction (YHD) is frequently prescribed to prevent and treat cardiovascular diseases. YHD inhibits platelet aggregation, however the underlying mechanisms are unclear. METHODS: The in vitro and in vivo anti-platelet and antithrombotic effects of YHD and ethanol-precipitated YHD (EYHD) and underlying mechanisms were investigated. Forty-six Sprague-Dawley (SD) rats and 36 male Kunming mice were examined. Ten SD rats were used to assess the cytotoxicity of YHD and EYHD by releasing lactate dehydrogenase from treated platelets. The remaining 36 SD rats were divided into six groups (six per group), including control saline (5 mL/kg), aspirin (20 mg/kg), YHD low dosage (0.2 g/kg), YHD high dosage (2.0 g/kg), 75% EYHD low dosage (0.2 g/kg), and 75% EYHD high dosage (2.0 g/kg) groups to detect platelet aggregation; the 36 Kunming mice were divided into 6 groups to detect mesenteric arterial thrombosis induction. Thromboxane B2 (TXB2) levels were determined by enzyme immunoassay. RESULTS: YHD high dosage and 75% EYHD (low and high dosage) inhibited ADP-induced platelet aggregation. Moreover, collagen-induced platelet aggregation was significantly suppressed by YHD (high dosage), 75% EYHD (high dosage), and 75% EYHD (low dose). Rats given 75% EYHD (high dose) displayed a marked reduction in collagen-induced platelet aggregation at 2 h post-administration. YHD and EYHD markedly prolonged the onset of thrombosis causing loose attachment of the thrombus to the vascular endothelium, but bleeding and clotting times were not significantly changed. Finally, YHD and EYHD markedly reduced TXB2 levels. CONCLUSIONS: YHD and EYHD effectively inhibit platelet activation and thrombosis, presumably by suppressing TXB2.

[Study on the Structure and Nanomechanical Properties of Organic Montmorillonite Reinforced Urea-Formaldehyde Adhesive].

Montmorillonite (MMT) is a natural mineral that has great potential as reinforcing filler in wood adhesives. In order to study the reinforcing mechanism more clearly, organic MMT-reinforced urea-formaldehyde adhesive (UF-OMMT) was prepared to analyze its chemical properties and crystal structure with Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). The nanomechanical properties of UF, UF-MMT and PF-OMMT adhesives in the interphase of wood-based composite were analyzed by nanoindentation (NI) and the macro-bonding strength of composite were also tested. The results of FTIR and XRD indicated that in the spectra of MMT modified by cetyltrimethyl ammonium bromide (CTAB), the new peaks appeared at 2 929 and 2 853 cm-1corresponding to C­H stretching vibrations of the organic intercalation agent (CTAB). The (001) diffraction peak of MMT was shifted to a lower angle and the lamellar repeat distance increases from 1.51 nm to 2.71 nm after organic modification. The ion exchange of the cations in montmorillonite with organic ammonium ions and the separating and disorder crystalline improved the compatibility of the modified clay with the polymers and the dispersion of the layers into the matrix. The good physical filling of MMT particles and the elastomer formed during the reaction could transfer and distribute loads between components more homogenously, therebycontributing to the improved mechanical properties of adhesives. As compared to the untreated UF, the reduced elastic modulus and hardness of UF-OMMT in the interphase increased by about 66.9% and 24.2%, respectively. At the macroscale, the bonding strength of plywood bonded with UF-OMMT increased by about 97% as compared to that of unmodified UF resin. The positive effects of montmorillonite on water and heat resistance can be attributed to the better barrier properties of the interphase.

Functionalized flattened bamboo board: In-situ immersion assembly of flame-retardant, waterproof and anti-mold composite coatings.

The flattened bamboo board (FB) represents a promising innovation in the bamboo industry. To address the challenges of flammability and hygroscopicity, composite coatings consisting of melamine (MEL), phytic acid (PA), cerium ions (Ce3+), and sodium laurate (La) are assembled on the FB surface through an in-situ impregnation strategy. The resulting MEL/PA-Ce3+@La FB exhibits exceptional flame retardancy. It achieves a V-0 rating in the vertical burning test (UL-94) and boasts a high limiting oxygen index (LOI) value of 38.5 %. The coated FB exhibits superhydrophobicity, evidenced by a water contact angle of 156.5°, which can be attributed to the in-situ growth of PA-Ce3+ complexes (for constructing micro/nanoscale coarse structures) and the modification with La (for reducing surface energy).This superhydrophobic surface imparts both self-cleaning and anti-mold properties to the coated FB. Moreover, the coated FB exhibits excellent mechanical stability, withstanding 36 cycles of sandpaper abrasion and tape peeling without losing its hydrophobicity. In summary, this work provides an innovative strategy for the bamboo processing industry to produce flattened bamboo boards with combined flame retardancy, superhydrophobic and anti-mold properties. Such versatility holds significant potential to facilitate the utilization of flattened bamboo boards in the construction and decorative materials industries.

Revealing climatic and groundwater impacts on the spatiotemporal variations in vegetation coverage in marine sedimentary basins of the North China Plain, China.

The North China Plain (NCP) is one of the three great plains in China and also serves as a vital region for grain, cotton, and oil production. Under the influence of regional hydrothermal changes, groundwater overexploitation, and seawater intrusion, the vegetation coverage is undergoing continuous alterations. However, a comprehensive assessment of impacts of precipitation, temperature, and groundwater on vegetation in marine sedimentary regions of the NCP is lacking. Heilonggang Basin (HB) is located in the low-lying plain area in the east of NCP, which is part of the NCP. In this study, the HB was chosen as a typical area of interest. We collected a series of data, including the Normalized Difference Vegetation Index (NDVI), precipitation, temperature, groundwater depth, and Total Dissolved Solids (TDS) from 2001 to 2020. Then the spatiotemporal variation in vegetation was analyzed, and the underlying driving mechanisms of vegetation variation were explored in this paper. The results show that NDVI experiences a rapid increase from 2001 to 2004, followed by stable fluctuations from 2004 to 2020. The vegetation in the HB has achieved an overall improvement in the past two decades, with 76% showing improvement, mainly in the central and eastern areas, and 24% exhibiting deterioration in other areas. From 2001 to 2020, NDVI correlates positively with precipitation, whereas its relationship with temperature fluctuates between positive and negative, and is not statistically significant. There is a threshold for the synergistic change of NDVI and groundwater depth. When the groundwater depth is lower than 3.8 m, NDVI increases sharply with groundwater depth. However, beyond this threshold, NDVI tends to stabilize and fluctuate. In the eastern coastal areas, NDVI exhibits a strong positive correlation with groundwater depth, influenced by the surface soil TDS controlled by groundwater depth. In the central regions, a strong negative correlation is observed, where NDVI is primarily impacted by soil moisture under the control of groundwater. In the west and south, a strong positive correlation exists, with NDVI primarily influenced by the intensity of groundwater exploitation. Thus, precipitation and groundwater are the primary driving forces behind the spatiotemporal variability of vegetation in the HB, while in contrast, the influence of temperature is uncertain. This study has elucidated the mechanism of vegetation response, providing a theoretical basis for mitigating adverse factors affecting vegetation growth and formulating rational water usage regulations in the NCP.

In situ retention of lignin-rich bamboo green effectively improves the surface properties of flattened bamboo.

Bamboo has tremendous carbon sequestration potential, and bamboo green is underutilized. This work devised a green-keeping technique in bamboo flattening that preserved natural bamboo green in-situ. The impacts of flattening and green-keeping on bamboo morphology, chemical composition, physical qualities, and composite applications were examined. Bamboo cells were wrinkled after flattening, while bamboo green exhibited a more homogenous surface. Bamboo cellulose crystallinity increased after flattening, hemicellulose deteriorated little, and relative lignin content increased. The hydrophobicity and mildew resistance of the surface of G-FB (green-kept flattened bamboo board) were improved. Compared to untreated bamboo, FB and G-FB had 61.1 % and 49.5 % higher tensile strength and 8.0 % and 33.2 % higher MOR. G-FB-made flooring exhibited a MOR of 134.7 MPa and upgraded surface properties. Bamboo green preservation boosted utilization of materials and improved flattened bamboo's exterior surface without affecting lamination bonding. Simple bamboo green preservation multifunctionalizes flattened bamboo composites.

Digital-Twin-Assisted Skill Learning for 3C Assembly Tasks.

The utilization of robots in computer, communication, and consumer electronics (3C) assembly has the potential to significantly reduce labor costs and enhance assembly efficiency. However, many typical scenarios in 3C assembly, such as the assembly of flexible printed circuits (FPCs), involve complex manipulations with long-horizon steps and high-precision requirements that cannot be effectively accomplished through manual programming or conventional skill-learning methods. To address this challenge, this article proposes a learning-based framework for the acquisition of complex 3C assembly skills assisted by a multimodal digital-twin environment. First, we construct a fully equivalent digital-twin environment based on the real-world counterpart, equipped with visual, tactile force, and proprioception information, and then collect multimodal demonstration data using virtual reality (VR) devices. Next, we construct a skill knowledge base through multimodal skill parsing of demonstration data, resulting in primitive policy sequences for achieving 3C assembly tasks. Finally, we train primitive policies via a combination of curriculum learning, residual reinforcement learning, and domain randomization methods and transfer the learned skill from the digital-twin environment to the real-world environment. The experiments are conducted to verify the effectiveness of our proposed method.

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Physical Exercise and Diet: Regulation of Gut Microbiota to Prevent and Treat Metabolic Disorders to Maintain Health.

Each person's body is host to a large number and variety of gut microbiota, which has been described as the second genome and plays an important role in the body's metabolic process and is closely related to health. It is common knowledge that proper physical activity and the right diet structure can keep us healthy, and in recent years, researchers have found that this boost to health may be related to the gut microbiota. Past studies have reported that physical activity and diet can modulate the compositional structure of the gut microbiota and further influence the production of key metabolites of the gut microbiota, which can be an effective way to improve body metabolism and prevent and treat related metabolic diseases. In this review, we outline the role of physical activity and diet in regulating gut microbiota and the key role that gut microbiota plays in improving metabolic disorders. In addition, we highlight the regulation of gut microbiota through appropriate physical exercise and diet to improve body metabolism and prevent metabolic diseases, aiming to promote public health and provide a new approach to treating such diseases.

Ameliorative effect of black tea extract on the skin of D-galactose-induced aging mice.

Aging is a universal and irreversible process, and the skin is an important feature that reflects the aging of the organism. Skin aging has been a focus of attention in recent years because it leads to changes in an individual's external features and the loss of many important biological functions. This experiment investigated the improvement effect of black tea extract (BTE) on the skin of aging mice under D-galactose induction. After 6 weeks of administration, the changes in skin bio-chemical indices and tissue structure were compared with the blank and positive control groups. It was observed that BTE increased water and hyaluronic acid (HA) content, decreased malondialdehyde (MDA) content, enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the skin of aging mice, and improved the structure of aging damaged skin tissues and increased the content of total collagen. The experimental results showed that BTE can play a significant anti-aging effect on the skin, which can be used as a functional food for aging inhibition.

Structure and Physical Properties of Conductive Bamboo Fiber Bundle Fabricated by Magnetron Sputtering.

The variety of conductive fibers has been constantly enriched in recent years, and it has made rapid development in the fields of electronic textiles, intelligent wearable, and medical care. However, the environmental damage caused by the use of large quantities of synthetic fibers cannot be ignored, and there is little research on conductive fibers in the field of bamboo, a green and sustainable material. In this work, we used the alkaline sodium sulfite method to remove lignin from bamboo, prepared a conductive bamboo fiber bundle by coating a copper film on single bamboo fiber bundles using DC magnetron sputtering, and analyzed its structure and physical properties under different process parameters, finding the most suitable preparation condition that combines cost and performance. The results of the scanning electron microscope show that the coverage of copper film can be improved by increasing the sputtering power and prolonging the sputtering time. The resistivity of the conductive bamboo fiber bundle decreased with the increase of the sputtering power and sputtering time, up to 0.22 Ω·mm; at the same time, the tensile strength of the conductive bamboo fiber bundle continuously decreased to 375.6 MPa. According to the X-ray diffraction results, Cu in the copper film on the surface of the conductive bamboo fiber bundle shows the preferred orientation of (111) the crystal plane, indicating that the prepared Cu film has high crystallinity and good film quality. X-ray photoelectron spectroscopy results show that Cu in the copper film exists in the form of Cu0 and Cu2+, and most are Cu0. Overall, the development of the conductive bamboo fiber bundle provides a research basis for the development of conductive fibers in a natural renewable direction.

Integrated bioinformatics analysis for identifying key genes and pathways in female and male patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common cause of heart failure, and males are more likely to suffer from DCM than females. This research aimed at exploring possible DCM-associated genes and their latent regulatory effects in female and male patients. WGCNA analysis found that in the yellow module, 341 and 367 key DEGs were identified in females and males, respectively. A total of 22 hub genes in females and 17 hub genes in males were identified from the PPI networks of the key DEGs based on Metascape database. And twelve and eight potential TFs of the key DEGs were also identified in females and males, respectively. Eight miRNAs of 15 key DEGs were screened in both females and males, which may be differentially expressed in females and males. Dual-luciferase reporter assay demonstrated that miR-21-5P could directly target the key gene MATN2. Furthermore, Sex differences in KEGG pathways were identified. Both KOBAS and GSEA analysis identified 19 significantly enriched pathways related to immune response in both females and males, and the TGF-ß signaling pathway was exclusively identified in males. Network pharmacology analysis revealed that seven key DEGs were potential targets for the treatment of DCM, of which the OLR1 gene was only identified in males, the expression levels of the seven genes were verified by RT-PCR. The above results could offer a novel understanding of sex differences in key genes and pathways in DCM progression.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors ß.

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors ß was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q²) was 0.571 and non-cross-validation correlation coefficient (r²) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results.