Exosomes: The endogenous nanomaterials packed with potential for diagnosis and treatment of neurologic disorders.

Neurologic disorders (NDs) are serious diseases that threaten public health. However, due to the complex pathogenesis and significant individual differences in traditional treatments, specific treatment methods for NDs are still lacking. Exosomes, the smallest extracellular vesicles secreted by eukaryotic cells, are receiving increasing attention in the field of NDs. They contain misfolded proteins related to various NDs, including amyloid-beta, Tau proteins, and α-synuclein, indicating their promising roles in the diagnosis and treatment of NDs. In this review, an overview of the biogenesis, composition, and biological functions of exosomes is provided. Moreover, we summarize their potential roles in the pathogenesis of three prevalent NDs (including Alzheimer's disease, Ischemic stroke, and Parkinson's disease). On this basis, the diagnostic potential and therapeutic value of exosomes carrying various bioactive molecules are discussed in detail. Also, the concerns and perspectives of exosome-based diagnosis and therapy are discussed.

Macaque Brainnetome Atlas: A multifaceted brain map with parcellation, connection, and histology.

The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data. The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections. The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images. As a demonstrative application, the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure. The resulting resource includes: (1) the thoroughly delineated Macaque Brainnetome Atlas (MacBNA), (2) regional connectivity profiles, (3) the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset (Brainnetome-8), and (4) multi-contrast MRI, neuronal-tracing, and histological images collected from a single macaque. MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function. Therefore, it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.

Diagnostic value of serum NLRP3, metalloproteinase-9 and interferon-γ for postoperative hydrocephalus and intracranial infection in patients with severe craniocerebral trauma.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. We unveiled the diagnostic value of serum NLRP3, metalloproteinase-9 (MMP-9) and interferon-γ (IFN-γ) levels in post-craniotomy intracranial infections and hydrocephalus in patients with severe craniocerebral trauma to investigate the high risk factors for these in patients with TBI, and the serological factors predicting prognosis, which had a certain clinical predictive value. Study subjects underwent bone flap resection surgery and were categorized into the intracranial infection/hydrocephalus/control (without postoperative hydrocephalus or intracranial infection) groups, with their clinical data documented. Serum levels of NLRP3, MMP-9 and IFN-γ were determined using ELISA kits, with their diagnostic efficacy on intracranial infections and hydrocephalus evaluated by receiver operating characteristic curve analysis. The independent risk factors affecting postoperative intracranial infections and hydrocephalus were analysed by logistic multifactorial regression. The remission after postoperative symptomatic treatment was counted. The intracranial infection/control groups had significant differences in Glasgow Coma Scale (GCS) scores, opened injury, surgical time and cerebrospinal fluid leakage, whereas the hydrocephalus and control groups had marked differences in GCS scores, cerebrospinal fluid leakage and subdural effusion. Serum NLRP3, MMP-9 and IFN-γ levels were elevated in patients with post-craniotomy intracranial infections/hydrocephalus. The area under the curve values of independent serum NLRP3, MMP-9, IFN-γ and their combination for diagnosing postoperative intracranial infection were 0.822, 0.722, 0.734 and 0.925, respectively, and for diagnosing hydrocephalus were 0.865, 0.828, 0.782 and 0.957, respectively. Serum NLRP3, MMP-9 and IFN-γ levels and serum NLRP3 and MMP-9 levels were independent risk factors influencing postoperative intracranial infection and postoperative hydrocephalus, respectively. Patients with hydrocephalus had a high remission rate after postoperative symptomatic treatment. Serum NLRP3, MMP-9 and IFN-γ levels had high diagnostic efficacy in patients with postoperative intracranial infection and hydrocephalus, among which serum NLRP3 level played a major role.

Glycol Monomethyl Ether-Substituted Carbazolyl Hole-Transporting Material for Stable Inverted Perovskite Solar Cells with Efficiency of 25.52.

Organic self-assembled molecules (OSAMs) based hole transporting materials play a pivotal role in achieving highly efficient and stable inverted perovskite solar cells (IPSCs). However, the reported carbazol-based OSAMs have serious drawbacks, such as poor solubility in alcohol solution, worse matched energy arrangement with perovskite, and limited molecular species, which greatly limit the device performance. To address above problems, a novel OSAM 4-(3,6-glycol monomethyl ether-9H-carbazol-9-yl) butyl]phosphonic acid (GM-4PACz) was synthesized as hole-transporting material by introducing glycol monomethyl ether (GM) side chains at carbazolyl unit. GM groups enhance the surface energy of Indium Tin Oxide (ITO)/SAM substrate to facilitate the nucleation and growth of up perovskite film, suppress cation defects, release the residual stress at SAM/perovskite interface, and evaluate energy level for matching with perovskite. Consequently, the GM-4PACz based IPSC achieves a champion PCE of 25.52%, a respectable open-circuit voltage (VOC) of 1.21 V, a high stability, possessing 93.29% and 91.75% of their initial efficiency after aging in air for 2000 h or tracking at maximum power point for 1000 h, respectively.

Development of new materials for electrothermal metals using data driven and machine learning.

After adopting a combined approach of data-driven methods and machine learning, the prediction of material performance and the optimization of composition design can significantly reduce the development time of materials at a lower cost. In this research, we employed four machine learning algorithms, including linear regression, ridge regression, support vector regression, and backpropagation neural networks, to develop predictive models for the electrical performance data of titanium alloys. Our focus was on two key objectives: resistivity and the temperature coefficient of resistance (TCR). Subsequently, leveraging the results of feature selection, we conducted an analysis to discern the impact of alloying elements on these two electrical properties.The prediction results indicate that for the resistivity data prediction task, the radial basis function kernel-based support vector machine model performs the best, with a correlation coefficient above 0.995 and a percentage error within 2%, demonstrating high predictive capability. For the TCR data prediction task, the best-performing model is a backpropagation neural network with two hidden layers, also with a correlation coefficient above 0.995 and a percentage error within 3%, demonstrating good generalization ability. The feature selection results using random forest and Xgboost indicate that Al and Zr have a significant positive effect on resistivity, while Al, Zr, and V have a significant negative effect on TCR. The conclusion of the composition optimization design suggests that to achieve both high resistivity and TCR, it is recommended to set the Al content in the range of 1.5% to 2% and the Zr content in the range of 2.5% to 3%.

Functional nanomaterials as photosensitizers or delivery systems for antibacterial photodynamic therapy.

Bacterial infection is a global health problem that closely related to various diseases threatening human life. Although antibiotic therapy has been the mainstream treatment method for various bacterial infectious diseases for decades, the increasing emergence of bacterial drug resistance has brought enormous challenges to the application of antibiotics. Therefore, developing novel antibacterial strategies is of great importance. By producing reactive oxygen species (ROS) with photosensitizers (PSs) under light irradiation, antibacterial photodynamic therapy (aPDT) has emerged as a non-invasive and promising approach for treating bacterial infections without causing drug resistance. However, the insufficient therapeutic penetration, poor hydrophilicity, and poor biocompatibility of traditional PSs greatly limit the efficacy of aPDT. Recently, studies have found that nanomaterials with characteristics of favorable photocatalytic activity, surface plasmonic resonance, easy modification, and high drug loading capacity can improve the therapeutic efficacy of aPDT. In this review, we aim to provide a comprehensive understanding of the mechanism of nanomaterials-mediated aPDT and summarize the representative nanomaterials in aPDT, either as PSs or carriers for PSs. In addition, the combination of advanced nanomaterials-mediated aPDT with other therapies, including targeted therapy, gas therapy, and multidrug resistance (MDR) therapy, is reviewed. Also, the concerns and possible solutions of nanomaterials-based aPDT are discussed. Overall, this review may provide theoretical basis and inspiration for the development of nanomaterials-based aPDT.

Peroxidase-like activity and mechanism of gold nanoparticle-modified Ti3C2 MXenes for the construction of H2O2 and ampicillin colorimetric sensors.

Transition metal carbides modified by Au nanoparticles (Au/Ti3C2) were synthesized and developed as a colorimetric sensor for the determination of H2O2 and ampicillin. The surface electrical properties of Ti3C2 were changed, and Au nanoparticles (AuNPs) and gold growth solution were synthesized simultaneously. Au/Ti3C2 was obtained by seed growth method with AuNPs modified on the surface of transition metal carbides, nitrides or carbon-nitrides (Ti3C2 MXenes). The synthesized AuNPs and Ti3C2 had no peroxidase-like activity, but Au/Ti3C2 had. The peroxidase catalytic mechanism was due to electron transfer. The peroxidase activity of Au/Ti3C2 can be utilized for the determination of H2O2. The linear range of Au/Ti3C2 for H2O2 was 1-60 µM, and the detection limit was 0.12 µM (S/N = 3). A colometric sensor for ampicillin detection based on Au/Ti3C2 was further constructed since S in ampicillin formed an Au-S bond with Au/Ti3C2, leading to the weakening of its peroxidase-like property. The change of peroxidase-like property attenuated oxidation of TMB, and the ampicillin content was inversely proportional to the concentration of oxidized TMB, and the blue color of solution faded, which enabled the determination of ampicillin. The linear range for ampicillin was 0.005-0.5 µg mL- 1, and the detection limit was 1.1 ng mL- 1 (S/N = 3). The sensor was applied to the detection of ampicillin in milk and human serum.

Layer-by-Layer Organic Solar Cells Enabled by 1,3,4-Selenadiazole-Containing Crystalline Small Molecule with Double-Fibril Network Morphology.

A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.

Crossbreeding Effect of Chalcogenation and Iodination on Benzene Additives Enables Optimized Morphology and 19.68% Efficiency of Organic Solar Cells.

Volatile solid additives have attracted increasing attention in optimizing the morphology and improving the performance of currently dominated non-fullerene acceptor-based organic solar cells (OSCs). However, the underlying principles governing the rational design of volatile solid additives remain elusive. Herein, a series of efficient volatile solid additives are successfully developed by the crossbreeding effect of chalcogenation and iodination for optimizing the morphology and improving the photovoltaic performances of OSCs. Five benzene derivatives of 1,4-dimethoxybenzene (DOB), 1-iodo-4-methoxybenzene (OIB), 1-iodo-4-methylthiobenzene (SIB), 1,4-dimethylthiobenzene (DSB) and 1,4-diiodobenzene (DIB) are systematically studied, where the widely used DIB is used as the reference. The effect of chalcogenation and iodination on the overall property is comprehensively investigated, which indicates that the versatile functional groups provided various types of noncovalent interactions with the host materials for modulating the morphology. Among them, SIB with the combination of sulphuration and iodination enabled more appropriate interactions with the host blend, giving rise to a highly ordered molecular packing and more favorable morphology. As a result, the binary OSCs based on PM6:L8-BO and PBTz-F:L8-BO as well as the ternary OSCs based on PBTz-F:PM6:L8-BO achieved impressive high PCEs of 18.87%, 18.81% and 19.68%, respectively, which are among the highest values for OSCs.

Reversing the Natural Drug Resistance of Gram-Negative Bacteria to Fusidic Acid via Forming Drug-Phospholipid Complex.

Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA-phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA-phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss of E. coli and 99.1% loss of P. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use.

Anti-skin aging effect of sea buckthorn proanthocyanidins in D-galactose-induced aging mice.

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action. The results reveal that SBP can alleviate the skin aging phenomenon caused by D-galactose-induced aging. It can also enhance the total antioxidant capacity in the body, thereby strengthening the body's antioxidant defense capability. In addition, SBP can effectively improve skin aging by regulating the TGF-ß1/Smads pathway and MMPs/TIMP system, increasing the relative content of Col I and tropoelastin, further maintaining the stability of collagen fiber and elastic fiber structure. These results will provide the development and production of the antioxidant function of cosmetics and health products, providing a new train of thought.

[Clinical Efficacy and Safety of Flumatinib in the Treatment of Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase].

OBJECTIVE: To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1, 2020 to March 31, 2022, who had never received any tyrosine kinase inhibitor (TKI) were included in the study. The patients were treated by flumatinib mesylate 600mg once daily. The hematologic, cytogenetic and molecular responses were assessed at 3-, 6- and 12-month, and adverse effects of the drug were evaluated. RESULTS: 31 patients were treated with flumatinib for≥3 months, of which 24 patients were treated for ≥6 months and 14 patients were treated for≥12 months. At 3rd month of treatment, 30 out of 31 patients achieved complete hematologic response (CHR); 24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR), of which 21 cases achieved complete cytogenetic response (CCyR); Among 25 patients who underwent molecular testing, 22 patients had BCR-ABLIS≤10%, including 10 patients with BCR-ABLIS≤0.1%, and 6 patients with BCR-ABLIS≤0.01%. At 6th month of treatment, 23 out of 24 patients achieved CHR; 17 patients underwent cytogenetic testing and all achieved CCyR; Among 23 patients who underwent molecular testing, 20 patients had BCR-ABLIS≤1%, including 16 patients with BCR-ABLIS≤0.1% and 12 patients with BCR-ABLIS≤0.01%. At 12nd month of treatment, all 14 patients achieved CHR and CCyR; Among them, 10 patients had BCR-ABLIS≤0.1%, including 9 patients with BCR-ABLIS≤0.01%. The grade Ⅲ/Ⅳ leukopenia, thrombocytopenia and anemia rates in the patients were 13.3%, 20.0% and 3.3%, respectively. One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity. The major non-hematologic adverse events were abnormal liver function (20%), diarrhea (10%), bone/joint pain (10%), muscle spasm (10%), rash (6.7%), acute kidney injury (6.7%) and nausea(3.3%), most of which were grade I-II. No patient experienced grade Ⅳ non-hematologic adverse events. No drug toxicity-related death occurred. CONCLUSION: Flumatinib mesglate, as the first-line treatment for newly diagnosed CML-CP, can enable the patients to achieve early and deep molecular and cytogenetic responses, and shows good safety.

Arthroscopic treatment of osteoid osteoma in the posterior proximal tibia: A case report and literature review.

BACKGROUND: Osteoid osteoma (OO) is a benign lesion characterized by an increased fibrous component in the bone marrow, presence of bone-like structures within the medullary cavity, and a surrounding sclerotic bone rim. Reports on OO located in the posterior proximal tibia are rare. CASE SUMMARY: Herein, we report the case of an 18-year-old male, admitted for the evaluation of right knee pain. The right knee pain had started 6 months prior without any apparent cause, which was notably severe at night, affecting sleep, and was exacerbated while climbing stairs or bearing weight. The patient also experienced pain on flexion. Three-dimensional computed tomography and magnetic resonance imaging revealed a nodular lesion beneath the cortical bone of the posterior medial plateau of the right tibia and an abnormal signal focus on the posterior lateral aspect of the right tibial plateau associated with extensive bone marrow edema. A small amount of fluid was present in the right knee joint capsule. The patient subsequently underwent arthroscopic excision of the OO. Postoperatively, there was significant relief of pain, and the knee range of motion returned to normal. CONCLUSION: Although OO in the posterior proximal tibia is a rare occurrence, it can be effectively excised through minimally invasive arthroscopic visualization.

Preparation of starch-palmitic acid complexes by three different starches: A comparative study using the method of heating treatment and autoclaving treatment.

Recent research emphasizes the growing importance of starch-lipid complexes due to their anti-digestibility ability, prompting a need to explore the impact of different starch sources and preparation methods on their properties. In this study, starch-palmitic acid (PA) complexes were prepared by three different starches including Tartary buckwheat starch (TBS), potato starch (PTS), and pea starch (PS) by heating treatment (HT) and autoclaving treatment (AT), respectively, and their physicochemical property and in vitro digestibility were systematically compared. The formation of the starch-PA complex was confirmed through various characterization techniques, including scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction. Among the complexes, the PTS-PA complex exhibited the highest complexation index over 80 %, while the PS-PA complex had the lowest rapid digestible starch content (56.49-59.42 %). Additionally, the complexes prepared by AT exhibited higher resistant starch content (41.95-32.46 %) than those prepared by HT (31.42-32.49 %), while the complexes prepared by HT held better freeze-thaw stability and hydration ability than those prepared by AT. This study highlights the important role of starch sources in the physicochemical and digestibility properties of starch-lipid complex and the potential application of AT in the preparation of novel resistant starch.

Rattan Pepper Polysaccharide Regulates DSS-Induced Intestinal Inflammation and Depressive Behavior through Microbiota-Gut-Brain Axis.

Inflammatory bowel disease (IBD) is a chronic and recurrent disease. Increasing evidence suggests a higher incidence of depression in IBD patients compared with the general population, but the underlying mechanism remains uncertain. Rattan pepper polysaccharide (RPP) is an important active ingredient of rattan pepper, yet its effects and mechanisms on intestinal inflammation and depression-like behavior remain largely unknown. This study aims to investigate the ameliorating effect of RPP on dextran sulfate sodium salt (DSS)-induced intestinal inflammation and depression-like behavior as well as to reveal its mechanism. Our results indicate that RPP effectively ameliorated intestinal microbiota imbalance and metabolic disorders of short-chain fatty acids (SCFAs) and bile acids in mice with DSS-induced inflammation, contributing to the recovery of intestinal Th17/Treg homeostasis. Importantly, RPP effectively alleviated brain inflammation caused by intestinal inflammatory factors entering the brain through the blood-brain barrier. This effect may be attributed to the inhibition of the TLR4/NF-κB signaling pathway, which alleviates neuroinflammation, and the activation of the CREB/BDNF signaling pathway, which improves synaptic dysfunction. Therefore, our findings suggest that RPP may play a role in alleviating DSS-induced gut inflammation and depression-like behavior through the microbiota-gut-brain axis.

Molecular Investigation and Preliminary Validation of Candidate Genes Associated with Neurological Damage in Heat Stroke.

Heat stroke (HS) is a severe medical condition characterized by a systemic inflammatory response that may precipitate multi-organ dysfunction, with a particular predilection for inducing profound central nervous system impairments. We aim to employ bioinformatics techniques for the retrieval and analysis of genes associated with heat stroke-induced neurological damage. We performed a comprehensive analysis of the GSE64778 dataset from the Sequence Read Archive, resulting in the identification of 1178 significantly differentially expressed genes (DEGs). We retrieved 2914 genes associated with heat stroke from the GeneCards database and 2377 genes associated with heat stroke from the Comparative Toxicogenomics Database (CTD). The intersection of the top 300 DEGs in the GSE64778 dataset intersected with the search results of GeneCards and CTD, yielding 25 final candidates for DEGs associated with heat stroke. Gene Ontology functional annotation results indicated that the target genes were mainly involved in apoptosis, stress response, and negative regulation of cellular processes and function in processes such as protein dimerization and protein binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed a predominant enrichment of candidate target genes within the PI3K-AKT signaling pathway. Subsequent protein-protein interaction network analysis highlighted HSP90aa1 as a central gene, indicating its pivotal role by possessing the highest number of edges among the genes enriched in the PI3K-AKT signaling pathway. Quantitative reverse transcription-polymerase chain reaction analysis performed on blood samples from patients validated the expression of Hsp90aa1 in individuals exhibiting early neurological damage in HS, consistent with the findings from the mRNA bioinformatics analysis. Additionally, the bioinformatics analysis of the upstream microRNAs (miRNAs) regulating HSP90aa1 and the target miRNAs associated with candidate long non-coding RNAs (lncRNAs) identified three lncRNAs, eight miRNAs, and one mRNA in the regulatory network. The DIANA Tools database and algorithms were employed for pathway enrichment and correlation analysis, revealing a significant association between LOC102547734 and MIR-206-3p, with the latter being identified as a target binding site Moreover, the analysis unveiled a correlation between MIR-206-3p and HSP90aa1, implicating the latter as a potential target binding site within the regulatory network.

METTL3-dependent N6-methyladenosine modification is involved in berberine-mediated neuroprotection in ischemic stroke by enhancing the stability of NEAT1 in astrocytes.

Ischemic stroke (IS) is one of the principal causes of disability and death worldwide. Berberine (BBR), derived from the traditional Chinese herbal medicine Huang Lian, has been reported to inhibit the progression of stroke, but the specific mechanism whereby BBR modulates the progression of ischemic stroke remains unclear. N6-methyladenosine (m6A) modification is the most typical epigenetic modification of mRNA post-transcriptional modifications, among which METTL3 is the most common methylation transferase. During the study, the middle cerebral artery occlusion/reperfusion (MCAO/R) was established in mice, and the mice primary astrocytes and neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro. Level of LncNEAT1, miR-377-3p was detected via RT-qPCR. The levels of Nampt and METTL3 were measured by Western blot. CCK8 and LDH assay was performed to detect cell viability. Here, we found that berberine alleviates MCAO/R-induced ischemic injury and up-regulates the expression of Nampt in astrocytes, miR-377-3p inhibits the expression of Nampt in astrocytes after OGD/R, thus promoting neuronal injury. NEAT1 binds to miR-377-3p in OGD/R astrocytes and plays a neuronal protective role as a ceRNA. METTL3 can enhance NEAT1 stability in OGD/R astrocytes by modulating m6A modification of NEAT1. Taken together, our results demonstrate that berberine exerts neuroprotective effects via the m6A methyltransferase METTL3, which regulates the NEAT1/miR-377-3p/Nampt axis in mouse astrocytes to ameliorate cerebral ischemia/reperfusion (I/R) injury.

Drug-free and multifunctional sodium bicarbonate/hyaluronic acid hybrid dressing for synergistic healing of infected wounds.

Skin wounds are susceptible to microbial infections which commonly lead to the delayed wound healing. Rapid clearance of pathogens from the wound is of great significance and importance for efficient healing of the infected wounds. Herein, we report a multifunctional hybrid dressing, which simply combines sodium bicarbonate (NaHCO3) and hyaluronic acid (HA) for the synergistic wound healing. Addition of NaHCO3 allows the hybrid dressing to have the great antibacterial and antioxidant activity, while maintaining the intrinsic skin repair function of HA. As a result, NaHCO3/HA hybrid dressing showed the great antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens, the ability to improve the fibroblasts proliferation and migration, the cell-protection capacity under H2O2-induced oxidative stress, and most importantly, the great healing efficacy for the mice wound infected by S. aureus. We further found that the epidermal regeneration, the collagen deposition and the angiogenesis were enhanced by NaHCO3/HA hybrid dressing. All these effects were NaHCO3 concentration-dependent. Since the NaHCO3/HA hybrid dressing is drug-free, easily fabricated, biocompatible, and efficient for wound healing, it may have great potentials for clinical management of infected wounds.

Advancement in Beneficial Effects of AVE 0991: A Brief Review.

AVE 0991, a non-peptide analogue of Angiotensin-(1-7) [Ang-(1-7)], is orally active and physiologically well tolerated. Several studies have demonstrated that AVE 0991 improves glucose and lipid metabolism, and contains anti-inflammatory, anti-apoptotic, anti-fibrosis, and anti-oxidant effects. Numerous preclinical studies have also reported that AVE 0991 appears to have beneficial effects on a variety of systemic diseases, including cardiovascular, liver, kidney, cancer, diabetes, and nervous system diseases. This study searched multiple literature databases, including PubMed, Web of Science, EMBASE, Google Scholar, Cochrane Library, and the ClinicalTrials.gov website from the establishment to October 2022, using AVE 0991 as a keyword. This literature search revealed that AVE 0991 could play different roles via various signaling pathways. However, the potential mechanisms of these effects need further elucidation. This review summarizes the benefits of AVE 0991 in several medical problems, including the COVID-19 pandemic. The paper also describes the underlying mechanisms of AVE 0991, giving in-depth insights and perspectives on the pharmaceutical value of AVE 0991 in drug discovery and development.

Multifunctional Regeneration Silicon-Loaded Chitosan Hydrogels for MRSA-Infected Diabetic Wound Healing.

Repeated microbial infection, excess reactive oxygen species (ROS) accumulation, cell dysfunction, and impaired angiogenesis under hyperglycemia severely inhibit diabetic wound healing. Therefore, developing multifunctional wound dressings accommodating the complex microenvironment of diabetic wounds is of great significance. Here, a multifunctional hydrogel (Regesi-CS) is prepared by loading regeneration silicon (Regesi) in the non-crosslinked chitosan (CS) solution, followed by freeze-drying and hydration. As expected, the blank non-crosslinked CS hydrogel (1%) shows great antibacterial activity against Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), improves fibroblast migration, and scavenges intracellular ROS. Interestingly, after loading 1% Regesi, the Regesi-CS (1%-1%) hydrogel shows greater antibacterial activity, significantly promotes fibroblasts proliferation and migration, scavenges much more ROS, and substantially protects fibroblasts under oxidative stress, yet Regesi alone has no or even negative effects. In the MRSA-infected diabetic wound model, Regesi-CS (1%-1%) hydrogel effectively promotes wound healing by eliminating bacterial infection, enhancing granulation tissue formation, promoting collagen deposition, and improving angiogenesis. In conclusion, Regesi-CS hydrogel may be a potential wound dressing for the effective treatment and management of chronic diabetic wounds.