Hydrosilylation Adducts to Produce Wide-Temperature Flexible Polysiloxane Aerogel under Ambient Temperature and Pressure Drying.

Despite incorporation of organic groups into silica-based aerogels to enhance their mechanical flexibility, the wide temperature reliability of the modified silicone aerogel is inevitably degraded. Therefore, facile synthesis of soft silicone aerogels with wide-temperature stability remains challenging. Herein, novel silicone aerogels containing a high content of Si are reported by using polydimethylvinylsiloxane (PDMVS), a hydrosilylation adduct with water-repellent groups, as a "flexible chain segment" embedded within the aerogel network. The poly(2-dimethoxymethylsilyl)ethylmethylvinylsiloxane (PDEMSEMVS) aerogel is fabricated through a cost-effective ambient temperature/pressure drying process. The optimized aerogel exhibits exceptional performance, such as ultra-low density (50 mg cm-3), wide-temperature mechanical flexibility, and super-hydrophobicity, in comparison to the previous polysiloxane aerogels. A significant reduction in the density of these aerogels is achieved while maintaining a high crosslinking density by synthesizing gel networks with well-defined macromolecules through hydrolytic polycondensation crosslinking of PDEMSEMVS. Notably, the pore/nanoparticle size of aerogels can be fine-tuned by optimizing the gel solvent type. The as-prepared silicone aerogels demonstrate selective absorption, efficient oil-water separation, and excellent thermal insulation properties, showing promising applications in oil/water separation and thermal protection.

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines.

Extracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to recipient cells and triggering cellular as well as biological responses. EVs have enormous potential for therapeutic applications as native or engineered exosomes. Native EVs are naturally released by cells without undergoing any modifications to either the exosomes or the cells that secrete them. In contrast, engineered EVs have been deliberately modified post-secretion or through genetic engineering of the secreting cells to alter their composition. Here we propose that engineered EVs displaying pathogen proteins could serve as promising alternatives to lipid nanoparticle (LNP)-mRNA vaccines. By leveraging their unique characteristics, these engineered EVs have the potential to overcome certain limitations associated with LNP-mRNA vaccines.

Design, synthesis and biological evaluation of thieno[3,2-c]pyrazol-urea derivatives as potent glycogen synthase kinase 3ß inhibitors based on the DFG-out conformation.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential therapeutic target for the treatment of a variety of human diseases. Here, we report the design and synthesis of a series of thieno[3,2-c]pyrazol-urea derivatives and evaluation of their GSK-3ß inhibitory activity. Among these analogues, the compound without substitution on terminal phenyl ring (3a) was found to be the most potent GSK-3ß inhibitor with an IC50 of 74.4 nM, while substitution on the terminal phenyl (3b-3p) led to decreased potency, independent of the position, size, or electronic properties of the substituents. Kinase selectivity assay revealed that 3a showed good selectivity over a panel of kinases, but was less selective over CDK1, CDK2 and CDK5. Additionally, the pharmacological properties of the synthesized compounds were investigated computationally by the SwissADME and the results showed that most of the compounds have good ADME profiles.

Engineering Sulfur-Containing Polymeric Fire-Retardant Coatings for Fire-Safe Rigid Polyurethane Foam.

With the advantages of lightweight and low thermal conductivity properties, polymeric foams are widely employed as thermal insulation materials for energy-saving buildings but suffer from inherent flammability. Flame-retardant coatings hold great promise for improving the fire safety of these foams without deteriorating the mechanical-physical properties of the foam. In this work, four kinds of sulfur-based flame-retardant copolymers are synthesized via a facile radical copolymerization. The sulfur-containing monomers serve as flame-retardant agents including vinyl sulfonic acid sodium (SPS), ethylene sulfonic acid sodium (VS), and sodium p-styrene sulfonate (VSS). Additionally, 2-hydroxyethyl acrylate (HEA) and 4-hydroxybutyl acrylate are employed to enable a strong interface adhesion with polymeric foams through interfacial H-bonding. By using as-synthesized waterborne flame-retardant polymeric coating with a thickness of 600 µm, the coated polyurethane foam (PUF) can achieve a desired V-0 rating during the vertical burning test with a high limiting oxygen index (LOI) of >31.5 vol%. By comparing these sulfur-containing polymeric fire-retardant coatings, poly(VS-co-HEA) coated PUF demonstrates the best interface adhesion capability and flame-retardant performance, with the lowest peak heat release rate of 166 kW m-2 and the highest LOI of 36.4 vol%. This work provides new avenues for the design and performance optimization of advanced fire-retardant polymeric coatings.

Safety and efficacy of day anterior cervical discectomy and fusion procedure for degenerative cervical spondylosis: a retrospective analysis.

OBJECTIVE: Our study aimed to develop a day anterior cervical discectomy and fusion (ACDF) procedure to treat degenerative cervical spondylosis (DCS). The goal was to analyze its clinical implications, safety, and early effects to provide a better surgical option for eligible DCS patients. METHODS: A retrospective analysis was performed to identify DCS patients who underwent day ACDF from September 2022 to August 2023. The operative time, intraoperative blood loss, postoperative drainage, preoperative and postoperative visual analog scale (VAS) scores, neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, JOA recovery rate (RR), incidence of dysphagia-related symptoms, 30-day hospital readmission rate, and incidence of other complications were recorded to evaluate early clinical outcomes. Radiography was performed to assess the location of the implants, neurological decompression, and cervical physiological curvature. RESULTS: All 33 patients (23 women and 10 men) underwent successful surgery and experienced significant symptomatic and neurological improvements. Among them, 26 patients underwent one-segment ACDF, 5 underwent two-segment ACDF, and 2 underwent three-segment ACDF. The average operative time was 71.1 ± 20.2 min, intraoperative blood loss was 19.1 ± 6.2 mL, and postoperative drainage was 9.6 ± 5.8 mL. The preoperative VAS and NDI scores improved postoperatively (7.1 ± 1.2 vs. 3.1 ± 1.3 and 66.7% ± 4.8% vs. 24.1% ± 2.5%, respectively), with a significant difference (P < 0.01). Moreover, the preoperative JOA scores improved significantly postoperatively (7.7 ± 1.3 vs. 14.2 ± 1.4; P < 0.01) with an RR of 93.9% in good or excellent. Postoperative dysphagia-related symptoms occurred in one patient (3.0%). During the follow-up period, no patient was readmitted within 30 days after discharge; however, an incisional hematoma was reported in one patient on the 6th day after discharge, which was cured by pressure dressing. The postoperative radiographs revealed perfect implant positions and sufficient nerve decompression in all patients. Furthermore, the preoperative cervical physiological curvature improved significantly after the operation (14.5° ± 4.0° vs. 26.3° ± 5.4°; P < 0.01). CONCLUSIONS: Day ACDF has good safety and early clinical efficacy, and it could be an appropriate choice for eligible DCS patients.

Effects of 0.4 T, 3.0 T and 9.4 T static magnetic fields on development, behaviour and immune response in zebrafish (Danio rerio).

Magnetic Resonance Imaging (MRI) is widely applied in medical diagnosis due to its excellent non-invasiveness. With the increasing intensity of static magnetic field (SMF), the safety assessment of MRI has been ongoing. In this study, zebrafish larvae were exposed to SMFs of 0.4, 3.0, and 9.4 T for 2 h (h), and we found that there was no significant difference in the number of spontaneous tail swings, heart rate, and body length of zebrafish larvae in the treatment groups. The expression of development-related genes shha, pygo1, mylz3 and runx2b in the three SMF groups was almost not significantly different from the control group. Behavior tests unveiled a notable reduction in both the average speed and duration of high-speed movements in zebrafish larvae across all three SMF groups. In addition, the 0.4 and 3.0 T SMFs increased the migration of neutrophils in caudal fin injury, and the expression of pro-inflammatory cytokines was also increased. To explore the mechanism of SMFs on zebrafish immune function, this study utilized aanat2-/- mutant fish to demonstrate the effect of melatonin (MT) involvement in SMFs on zebrafish immune function. This study provides experimental data for understanding the effects of SMFs on organisms, and also provides a new insight for exploring the relationship between magnetic fields and immune function.

Predicting long-term prognosis after percutaneous coronary intervention in patients with new onset ST-elevation myocardial infarction: development and external validation of a nomogram model.

BACKGROUND: The triglyceride glucose (TyG) index is a well-established biomarker for insulin resistance (IR) that shows correlation with poor outcomes in patients with coronary artery disease. We aimed to integrate the TyG index with clinical data in a prediction nomogram for the long-term prognosis of new onset ST-elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) . METHODS: This retrospective study included new-onset STEMI patients admitted at two heart centers for emergency PCI from December 2015 to March 2018 in development and independent validation cohorts. Potential risk factors were screened applying least absolute shrinkage and selection operator (LASSO) regression. Multiple Cox regression was employed to identify independent risk factors for prediction nomogram construction. Nomogram performance was assessed based on receiver operating characteristic curve analysis, calibration curves, Harrell's C-index and decision curve analysis (DCA). RESULTS: In total, 404 patients were assigned to the development cohort and 169 to the independent validation cohort. The constructed nomogram included four clinical variables: age, diabetes mellitus, current smoking, and TyG index. The Harrell's C-index values for the nomogram were 0.772 (95% confidence interval [CI]: 0.721-0.823) in the development cohort and 0.736 (95%CI: 0.656-0.816) in the independent validation cohort. Significant correlation was found between the predicted and actual outcomes in both cohorts, indicating that the nomogram is well calibrated. DCA confirmed the clinical value of the development prediction nomogram. CONCLUSIONS: Our validated prediction nomogram based on the TyG index and electronic health records data was shown to provide accurate and reliable discrimination of new-onset STEMI patients at high- and low-risk for major adverse cardiac events at 2, 3 and 5 years following emergency PCI.

Development of an assay system for the analysis of host RISC activity in the presence of a potyvirus RNA silencing suppressor, HC-Pro.

BACKGROUND: To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR. METHODS: Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency. RESULTS: Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity. CONCLUSIONS: In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.

Multimodal data-driven prognostic model for predicting new-onset ST-elevation myocardial infarction following emergency percutaneous coronary intervention.

OBJECTIVES: We developed a nomogram model derived from inflammatory indices, clinical data, and imaging data to predict in-hospital major adverse cardiac and cerebrovascular events (MACCEs) following emergency percutaneous coronary intervention (PCI) in patients with new-onset ST-elevation myocardial infarction (STEMI). METHODS: Patients with new-onset STEMI admitted between June 2020 and November 2022 were retrospectively reviewed. Data pertaining to coronary angiograms, clinical data, biochemical indices, and in-hospital clinical outcomes were derived from electronic medical records. Lasso regression model was employed to screen risk factors and construct a prediction model. RESULTS: Overall, 547 patients with new-onset STEMI who underwent PCI were included and assigned to the training cohort (n = 384) and independent verification cohort (n = 163). Six clinical features (age, diabetes mellitus, current smoking, hyperuricemia, neutrophil-to-lymphocyte ratio, and Gensini score) were selected by LASSO regression to construct a nomogram to predict the risk of in-hospital MACCEs. The area-under-the-curve (AUC) values for in-hospital MACCEs risk in the training and independent verification cohorts were 0.921 (95% CI 0.881-0.961) and 0.898 (95% CI 0.821-0.976), respectively. It was adequately calibrated in both training cohort and independent verification cohorts, and predictions were correlated with actual outcomes. Decision curve analysis demonstrated that the nomogram was capable of predicting in-hospital MACCEs with good clinical benefit. CONCLUSIONS: Our prediction nomogram based on multi-modal data (inflammatory indices, clinical and imaging data) reliably predicted in-hospital MACCEs in new-onset STEMI patients with emergency PCI. This prediction nomogram can enable individualized treatment strategies.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3ß inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3ß inhibitor with an IC50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aß-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3ß by up-regulating the expression of phosphorylated GSK-3ß at Ser9 and down-regulating the expression of phosphorylated GSK-3ß at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl3-induced zebrafish AD model, 54 significantly ameliorated the AlCl3-induced dyskinesia, demonstrating its anti-AD activity in vivo.