Emerging Antiarrhythmic Drugs for Atrial Fibrillation

Atrial fibrillation (AF), the most common cardiac arrhythmia worldwide, is driven by complex mechanisms that differ between subgroups of patients. This complexity is apparent from the different forms in which AF presents itself (post-operative, paroxysmal and persistent), each with heterogeneous patterns and variable progression. Our current understanding of the mechanisms responsible for initiation, maintenance and progression of the different forms of AF has increased significantly in recent years. Nevertheless, antiarrhythmic drugs for the management of AF have not been developed based on the underlying arrhythmia mechanisms and none of the currently used drugs were specifically developed to target AF. With the increased knowledge on the mechanisms underlying different forms of AF, new opportunities for developing more effective and safer AF therapies are emerging. In this review, we provide an overview of potential novel antiarrhythmic approaches based on the underlying mechanisms of AF, focusing both on the development of novel antiarrhythmic agents and on the possibility of repurposing already marketed drugs. In addition, we discuss the opportunity of targeting some of the key players involved in the underlying AF mechanisms, such as ryanodine receptor type-2 (RyR2) channels and atrial-selective K⁺-currents (I_K2P and I_SK) for antiarrhythmic therapy. In addition, we highlight the opportunities for targeting components of inflammatory signaling (e.g., the NLRP3-inflammasome) and upstream mechanisms targeting fibroblast function to prevent structural remodeling and progression of AF. Finally, we critically appraise emerging antiarrhythmic drug principles and future directions for antiarrhythmic drug development, as well as their potential for improving AF management.     

Effect of high carbon dioxide atmosphere packaging and soluble gas stabilization pre-treatment on the shelf-life and quality of chicken drumsticks

The effects of an aerobic modified atmosphere packaging (MAP) (70% CO₂, 15% O₂ and 15% N₂) with and without a CO₂ 3-h soluble gas stabilization (SGS) pre-treatment of chicken drumsticks were determined for various package and product quality characteristics. The CO₂ dissolved into drumsticks was determined. The equilibrium between CO₂ dissolved in drumsticks and CO₂ in head space was reached within 48 h after packaging, showing highest values of CO₂ in SGS pre-treated samples. This greater availability of CO₂ resulted in lower counts of TAB and Pseudomonas in SGS than in MAP drumsticks. Package collapse was significantly reduced in SGS samples. The average of CO₂ dissolved in the MAP treatment was 567 mg CO₂ kg^− 1 of chicken and, 361 mg CO₂ kg^− 1 of chicken during the MAP treatment, in SGS pre-treated samples. This difference could be the quantity of CO₂ dissolved during SGS pre-treatment.     

A queuing theory model for cloud computing

The ability to deliver guaranteed QoS (Quality of Service) is crucial for the commercial success of cloud platforms. This paper presents a model based on queuing theory to study computer service QoS in cloud computing. Cloud platforms are modeled with an open Jackson network that can be used to determine and measure the QoS guarantees the cloud can offer regarding the response time. The analysis can be performed according to different parameters, such as the arrival rate of customer services and the number and service rate of processing servers, among others. Detailed results for the model are presented. When scaling the system and depending on the types of bottleneck in the system, we show how our model can provide us with the best option to guarantee QoS. The results obtained confirm the usefulness of the model presented for designing real cloud computing systems.     

Dual Costimulatory and Coinhibitory Targeting with a Hybrid Fusion Protein as an Immunomodulatory Therapy in Lupus Nephritis Mice Models

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28—CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1–PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy.     

The catalytic activity of the Pr2Zr2−xFexO7±δ system for the CO oxidation reaction

One of the alternatives to decrease the concentration of CO is its oxidation reaction to CO₂, which can be made more efficient using catalysts. In this work, it is shown that pyrochlore structures are a promising candidate to act as heterogeneous catalysts due to their chemical and physical properties. For use as a catalyst in this reaction, the Pr₂Zr_2−xFe_xO_7±δ (x = 0, 0.05, 0.10, and 0.15) system was synthesized by the solvothermal method, firing the powder obtained at temperatures of 1200 and 1400°C. The diffraction patterns confirmed the pyrochlore structure as the single phase in all the nominal compositions. The Brunauer–Emmett–Teller method and dynamic light-scattering analysis showed an increase in the particle size and a decrease in the specific surface area when increasing the iron concentration and increasing the calcination temperature. The compositions that presented the best catalytic activity were the samples with the highest iron concentration. Moreover, these samples were able to convert all the CO oxidation reactions in a narrower temperature range than a conventional CeO₂ sample. The presence of vacancies and the redox behavior of the elements present are the key factors for the catalysis of this system in the CO oxidation reaction.     

Is Soft Carbon a More Suitable Match for SiOx in Li-Ion Battery Anodes? (Small 37/2023)

Silicon oxide (SiO_x), inheriting the high-capacity characteristic of silicon-based materials but possessing superior cycling stability, is a promising anode material for next-generation Li-ion batteries. SiO_x is typically applied in combination with graphite (Gr), but the limited cycling durability of the SiO_x/Gr composites curtails large-scale applications. In this work, this limited durability is demonstrated in part related to the presence of a bidirectional diffusion at the SiO_x/Gr interface, which is driven by their intrinsic working potential differences and the concentration gradients. When Li on the Li-rich surface of SiO_x is captured by Gr, the SiO_x surface shrinks, hindering further lithiation. The use of soft carbon (SC) instead of Gr can prevent such instability is further demonstrated. The higher working potential of SC avoids bidirectional diffusion and surface compression thus allowing further lithiation. In this scenario, the evolution of the Li concentration gradient in SiO_x conforms to its spontaneous lithiation process, benefiting the electrochemical performance. These results highlight the focus on the working potential of carbon as a strategy for rational optimization of SiO_x/C composites toward improved battery performance.     

A High-Rate Li–CO2 Battery Enabled by 2D Medium-Entropy Catalyst

Lithium-air batteries based on CO₂ reactant (Li–CO₂) have recently been of interest because it has been found that reversible Li/CO₂ electrochemistry is feasible. In this study, a new medium-entropy cathode catalyst, (NbTa)_0.5BiS₃, that enables the reversible electrochemistry to operate at high rates is presented. This medium entropy cathode catalyst is combined with an ionic liquid-based electrolyte blend to give a Li–CO₂ battery that operates at high current density of 5000 mA g⁻¹ and capacity of 5000 mAh g⁻¹ for up to 125 cycles, far exceeding reported values in the literature for this type of battery. The higher rate performance is believed to be due to the greater stability of the multi-element (NbTa)_0.5BiS₃ catalyst because of its higher entropy compared to previously used catalysts with a smaller number of elements with lower entropies. Evidence for this comes from computational studies giving very low surface energies (high surface stability) for (NbTa)_0.5BiS₃ and transmission electron microscopystudies showing the structure being retained after cycling. In addition, the calculations indicate that Nb-terminated surface promotes Li–CO₂ electrochemistry resulting in Li₂CO₃ and carbon formation, consistent with the products found in the cell. These results open new direction to design and develop high-performance Li–CO₂ batteries.     

Chiral Seeded Growth of Gold Nanorods Into Fourfold Twisted Nanoparticles with Plasmonic Optical Activity

A robust and reproducible methodology to prepare stable inorganic nanoparticles with chiral morphology may hold the key to the practical utilization of these materials. An optimized chiral growth method to prepare fourfold twisted gold nanorods is described herein, where the amino acid cysteine is used as a dissymmetry inducer. Four tilted ridges are found to develop on the surface of single-crystal nanorods upon repeated reduction of HAuCl₄, in the presence of cysteine as the chiral inducer and ascorbic acid as a reducing agent. From detailed electron microscopy analysis of the crystallographic structures, it is proposed that the dissymmetry results from the development of chiral facets in the form of protrusions (tilted ridges) on the initial nanorods, eventually leading to a twisted shape. The role of cysteine is attributed to assisting enantioselective facet evolution, which is supported by density functional theory simulations of the surface energies, modified upon adsorption of the chiral molecule. The development of R-type and S-type chiral structures (small facets, terraces, or kinks) would thus be non-equal, removing the mirror symmetry of the Au NR and in turn resulting in a markedly chiral morphology with high plasmonic optical activity.     

Improving glass-fiber epoxy composites via interlayer toughening with polyacrylonitrile/multiwalled carbon nanotubes electrospun fibers

The development of innovative engineered epoxy composites aiming to manufacture cost-efficient materials with reduced weight and enhanced physical properties remains as a current industrial challenge. In this work we report an original procedure for manufacturing glass-fiber epoxy reinforced nanocomposites (GFECs) by employing electrospun fiber-mats as a reinforcing phase. These fibers have been produced from polyacrylonitrile and multiwalled carbon nanotubes solutions. Optimal protocols are designed by combining Taguchi method with the morphological, structural and mechanical properties obtained by scanning electron microscopy, profilometry and tensile tests. It is demonstrated that GFECs fabricated using GF800 glass fiber show an improvement/enhancement of the mechanical properties with a fracture strain up to 500 MPa (around 20% higher than the non-reinforced epoxy composite counterpart). It is also shown that GFECs fabricated using GF3M glass fiber exhibited a reduction of the roughness up to 56%, which corresponds with a roughness improvement from N8 to N7 following the guidelines provided by the ISO 1302. These results suggest that this type of nanocomposites would be suitable to be used in the aeronautics and automotive industries.