Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Electromagnetically induced transparency enabled by quasi-bound states in the continuum modulated by epsilon-near-zero materials.

Highly tunable electromagnetically induced transparency (EIT) with high-quality-factor (Q-factor) excited by combining with the quasi-bound states in the continuum (quasi-BIC) resonances is crucial for many applications. This paper describes all-dielectric metasurface composed of silicon cuboid etched with two rectangular holes into a unit cell and periodically arranged on a SiO2 substrate. By breaking the C2 rotational symmetry of the unit cell, a high-Q factor EIT and double quasi-BIC resonant modes are excited at 1224.3, 1251.9 and 1299.6 nm with quality factors of 7604, 10064 and 15503, respectively. We show that the EIT resonance is caused by destructive interference between magnetic dipole resonances and quasi-BIC dominated by electric quadrupole. Toroidal dipole (TD) and electric quadrupole (EQ) dominate the other two quasi-BICs. The EIT window can be successfully modulated with transmission intensity from 90% to 5% and modulation depths ranging from -17 to 24 dB at 1200-1250 nm by integrating the metasurface with an epsilon-near-zero (ENZ) material indium tin oxide (ITO) film. Our findings pave the way for the development of applications such as optical switches and modulators with many potential applications in nonlinear optics, filters, and multichannel biosensors.

A Randomized Controlled Trial of Vertebral Body Decompression Procedure Versus Conservative Treatment for Painful Vertebral Compression Fracture.

Background: Traditional treatment modalities for vertebral compression fractures (VCFs) include bed rest, pain medications, muscle relaxants, back braces, and physical therapy. In cases where conservative treatment proves ineffective, a new procedure called core decompression of the vertebral body is explored. Core decompression of the vertebral body has the potential to lower and stabilize the intraosseous pressure, resulting in enhanced blood circulation, which contributes to pain reduction. In this trial, we evaluated the efficacy of core decompression of the vertebral body in patients with painful VCFs compared with conventional conservative treatment. Methods: This prospective randomized controlled trial was conducted at a tertiary education hospital between June 2017 and May 2020. The participants were randomly assigned in a 1:1 ratio to one of two treatment groups: the core decompression group and the conservative treatment group. The primary outcome measure was the visual analog scale (VAS) pain score of the back 3 months after the procedure. Secondary outcome measures included the Oswestry Disability Index (ODI) for lumbar disabilities, the European Quality of Life-5 Dimensions (EQ-5D) score for quality of life, and radiographic outcomes such as changes in compression rate. Results: All patients underwent the assigned intervention (48 core decompression and 50 conservative treatments). At both 1 month and 3 months, there were no significant differences between the core decompression group and conservative treatment group in VAS pain score (adjusted treatment effect: -0.1 and 2.0; 95% confidence interval [CI]: -7.5 to 7.3 and -5.6 to 9.6; p = 0.970 and p = 0.601, respectively). In addition, there were no significant inter-group differences in ODI and EQ-5D scores throughout the follow-up period (p = 0.917 and 0.704, respectively). Conclusion: Core decompression of the vertebral body did not demonstrate any significant improvement in pain and disability compared to conventional conservative treatment.

Evaluating the Efficacy of Water-Soluble Bone Wax (Tableau Wax) in Reducing Blood Loss in Spinal Fusion Surgery: A Randomized, Controlled, Pilot Study.

Background and Objectives: Lumbar decompression with fusion surgery is an effective treatment for spinal stenosis, but critical postoperative hematoma is a concern. Bone wax has been widely used to control bone bleeding but it has some drawbacks. This study aimed to evaluate the efficacy of Tableau wax, a bioabsorbable hemostatic material, in patients undergoing spinal fusion surgery through a pilot study design. Materials and Methods: A total of 31 patients were enrolled in this single-surgeon, single-institution study. The participants underwent transforaminal lumbar interbody fusion surgery and were randomly assigned to the control group (Bone wax) or test group (Tableau wax). Demographic data, pre- and post-operative hemoglobin levels, blood loss volume, surgical time, Oswestry Disability Index, and EQ-5D scores were recorded. Results: The study showed no significant difference in preoperative and postoperative hemoglobin levels, Oswestry Disability Index, and EQ-5D scores between the groups. However, the Tableau wax group had a significantly lower reduction in hemoglobin levels (1.3 ± 1.0 g/dL) and blood loss (438.2 mL) compared to the Bone wax group (2.2 ± 0.9 g/dL and 663.1 mL, respectively; p = 0.018 and p = 0.022).

Modular Synthesis of Tetrasubstituted Pyrroles through a Four-Component Cyclization Strategy Using Ammonium Salt as the Nitrogen Source.

A four-component synthesis of tetrasubstituted pyrroles was developed under metal-free conditions. The pyrrole ring was formed in one pot through [2 + 1 + 1 + 1] condensation using ammonium salt as the nitrogen source. In this strategy, 1,4-naphthoquinones and maleimides were used as the versatile C2 fragments to provide substituted benzo[f]isoindole-4,9-diones and pyrrolo[3,4-c]pyrrole-1,3-diones, respectively. This work is highlighted by using ammonium salt as the nitrogen source, readily available starting materials and multibond formation (two C-C and two C-N bonds) in a single operation.

Metal- and Solvent-Free Synthesis of Tetrahydrobenzo[c]carbazolones through NaI-Catalyzed Formal [4 + 2] Annulation.

A novel strategy for the preparation of functional carbazoles through NaI-catalyzed formal [4 + 2] annulation of 2-(indol-3-yl)cyclohexanones and alkynes/alkenes has been developed. The present approach started from easily available raw materials and provided a variety of tetrahydrobenzo[c]carbazolones in satisfactory yields under metal- and solvent-free conditions. Furthermore, the products could be further transformed into structurally valuable carbazole-based conjugated derivatives.

Effectiveness of the Iron Chelator CN128 in Mitigating the Formation of Dopamine Oxidation Products Associated with the Progression of Parkinson's Disease.

The occurrence and progression of Parkinson's disease (PD) has been associated with the observation of elevated iron concentrations in the substantia nigra pars compacta (SNpc). While the reasons for the impact of elevated iron concentrations remain unclear, one hypothesis is that the presence of labile iron induces the oxidation of dopamine (DA) to toxic quinones such as aminochrome (DAC) and reactive oxygen species (ROS). As such, one of the proposed therapeutic strategies has been the use of iron chelators such as deferiprone (DFP) (which is recognized to have limitations related to its rapid degradation in the liver) to reduce the concentration of labile iron. In this study, a detailed investigation regarding the novel iron chelator, CN128, was conducted and a kinetic model developed to elucidate the fundamental behavior of this chelator. The results in this work reveal that CN128 is effective in alleviating the toxicity induced by iron and DA to neurons when DA is present at moderate concentrations. When all the iron is chelated by CN128, the formation of DAC and the oxidation of DA can be reduced to levels identical to that in the absence of iron. The production of H2O2 is lower than that generated via the autoxidation of the same amount of DA. However, when severe leakage of DA occurs, the application of CN128 is insufficient to alleviate the associated toxicity. This is attibuted to the less important role of iron in the production of toxic intermediates at high concentrations of DA. CN128 is superior to DFP with regard to the reduction in formation of DAC and elevation in DA concentration. In summary, the results of this study suggest that prodromal application of the chelator CN128 could be effective in preventing the onset and slowing the early stage development of PD symptoms associated with oxidants and toxic intermediates resulting from the iron-mediated oxidation of the neurotransmitter dopamine with CN128 likely to be superior to DFP in view of its greater in vivo availability and less problematic side effects.

UVC upconversion material under sunlight excitation: LiYF(4): Pr(3+).

UVC upconversion emission is observed in a LiYF4:Pr3+ microcrystal under sunlight excitation. The dependence of UVC UC emission intensity on the excitation density of a 488 nm laser and sunlight is investigated. The obtained data indicates that two-photon processes play an important role in UVC UC emission. The UVC UC mechanisms of Pr3+ under the excitation of a laser and sunlight are presented and discussed. The UVC emission under sunlight excitation has broad prospects for application.