Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma

Asthma is a prevalent respiratory condition with multifaceted pathomechanisms, presenting challenges for therapeutic development. The SLC (Solute Carrier) gene family, encompassing diverse membrane transport proteins, plays pivotal roles in various human diseases by facilitating solute movement across biological membranes. These solutes include ions, sugars, amino acids, neurotransmitters, and drugs. Mutations in these ion channels have been associated with numerous disorders, underscoring the significance of SLC gene families in physiological processes. Among these, the SLC26A4 gene encodes pendrin, an anion exchange protein involved in transmembrane transport of chloride, iodide, and bicarbonate. Mutations in SLC26A4 are associated with Pendred syndrome. Elevated SLC26A4 expression has been linked to airway inflammation, hyperreactivity, and mucus production in asthma. Here, we review novel insights from SLC gene family members into the mechanisms of substrate transport and disease associations, with specific emphasis on SLC26A4. We explore triggers inducing SLC26A4 expression and its contributions to the pathogenesis of pulmonary diseases, particularly asthma. We summarize the inhibitors of SLC26A4 that have shown promise in the treatment of different phenotypes of diseases. While SLC26A4 inhibitors present potential treatments for asthma, further research is imperative to delineate their precise role in asthma pathogenesis and develop efficacious therapeutic strategies targeting this protein.

An Integer Programming Approach to Multi-Trip Routing of Delivery Drones at Load-Dependent Flight Speed

In recent years, there has been a growing interest in utilizing drones for parcel delivery among companies, aiming to address logistical challenges. However, effective optimization of delivery routes is essential. A theoretical framework termed the Flight Speed-aware Vehicle Routing Problem (FSVRP) has emerged to address the variability in drone flight speed based on payload weight. Several approximate methods have been proposed to solve the FSVRP. Our research endeavors to optimize parcel delivery efficiency and reduce delivery times by introducing a novel delivery problem. This problem accounts for multiple deliveries while considering the variability in flight speed due to diverse payloads. Through experimentation, we evaluate the efficacy of our proposed method compared to existing approaches. Specifically, we assess total flight distance and flight time. Our findings indicate that even in cases where the payload exceeds maximum capacity, all parcels can be delivered through multiple trips. Furthermore, employing a multi-trip FSVRP approach results in an average reduction of 10% in total flight time, even when payload capacities are not exceeded.

Sulforaphane’s Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-Dependent and -Independent Mechanism of Anti-SARS-CoV-2 Activity

It is well established that Nrf2 plays a crucial role in anti-oxidant and anti-inflammatory functions. However, its antiviral capabilities remain less explored. Despite this, several Nrf2 activators have demonstrated anti-SARS-CoV-2 properties, though the mechanisms behind these effects are not fully understood. In this study, using two mouse models of SARS-CoV-2 infection, we observed that the absence of Nrf2 significantly increased viral load and altered inflammatory responses. Additionally, we evaluated five Nrf2 modulators. Notably, epigallocatechin gallate (EGCG), sulforaphane (SFN), and dimethyl fumarate (DMF) exhibited significant antiviral effects, with SFN being the most effective. SFN did not impact viral entry but appeared to inhibit the main protease (M^Pro) of SARS-CoV-2, encoded by the Nsp5 gene, as indicated by two protease inhibition assays. Moreover, using two Nrf2 knockout cell lines, we confirmed that SFN's antiviral activity occurs independently of Nrf2 activation in vitro. Paradoxically, in vivo tests using the MA30 model showed that SFN's antiviral function was completely lost in Nrf2 knockout mice. Thus, although SFN and potentially other Nrf2 modulators can inhibit SARS-CoV-2 independently of Nrf2 activation in cell models, their Nrf2-dependent activities might be crucial for antiviral defense under physiological conditions. 

High Entropy Oxides: Next-Generation Air Electrodes for Reversible Protonic Solid Oxide Cells

Reversible protonic solid oxide cell (P-SOC) operating at intermediate-temperature exhibits excellent potential as a power generation and green hydrogen production device in fuel cell and electrolysis cell modes because of the high conversion efficiency. However, the lack of efficient air electrodes is the main challenge to obtain P-SOC with remarkable performance. Typically, air electrodes should possess high proton, oxygen ion and electron conductivity, outstanding catalytic ability for oxygen reduction reaction and H₂O splitting, and also long-term durability. Recently, high entropy oxides (HEO) have become popular due to their various potential applications in terms of outstanding properties, including catalysis ability, conductivity, thermal stability, etc. HEO air electrodes have been confirmed to show good electrochemical performance in P-SOC, but the complex compositions and structure make it difficult to study HEO by traditional experimental methods. Machine learning (ML) has been regarded as a powerful tool in materials research and can solve the drawbacks in the discovery of HEO in a traditional way. In this perspective, we not only discuss the current utilization of HEO in P-SOC but also provide a possible process to use ML to guide the development of HEO.

Green Chemical Technology: A New Journal for Green Engineering and Green Technology

Cytosine Deaminase-Assisted Mutator for Genome Evolution in Cupriavidus necator

Cupriavidus necator H16 has been intensively explored for its potential as a versatile microbial cell factory, especially for its CO₂ fixation capability over the past few decades. However, rational metabolic engineering remains challenging in the construction of microbial cell factories with complex phenotypes due to the limited understanding of its metabolic regulatory network. To overcome this obstacle, laboratory adaptive evolution emerges as an alternative. In the present study, CAM (cytosine deaminase-assisted mutator) was established for the genome evolution of C. necator, addressing the issue of low mutation rates. By fusing cytosine deaminase with single-stranded binding proteins, CAM introduced genome-wide C-to-T mutations during DNA replication. This innovative approach could boost mutation rates, thereby expediting laboratory adaptive evolution. The applications of CAM were demonstrated in improving cell factory robustness and substrate utilization, with H₂O₂ resistance and ethylene glycol utilization as illustrative case studies. This genetic tool not only facilitates the development of efficient cell factories but also opens avenues for exploring the intricate phenotype-genotype relationships in C. necator.

Unraveling Novel Strategies: Targeting Miz1 for Degradation to Enhance Antiviral Defense against Influenza A Virus

The ubiquitin system has been shown to play an important role in regulation of immune responses during viral infection. In a recent article published in Science Signaling, Wu and colleagues revealed that transcriptional factor Miz1 plays a pro-viral role in influenza A virus (IAV) infection by suppressing type I interferons (IFNs) production through recruiting HDAC1 to ifnb1 promoter. They show that a series of E3 ligases combinatorially regulates Miz1 ubiquitination and degradation and modulates IFNs production and viral replication.

Rurality: Why This Is Important

Biobased Vitrimers: A Sustainable Future

Vitrimers are crosslinked polymers containing dynamic covalent linkages. Because of their crosslinked structure, they are stable as thermosets at their service temperatures. At high enough temperatures, dynamic exchange reactions occur and rearrange the polymer network, thus vitrimers become malleable and reprocessable like thermoplastics. The dynamic covalent bonds can also undergo dissociative cleavage reactions under specific conditions, so vitrimers are inherently degradable. To achieve a sustainable future, various biomass resources have been used as raw materials in vitrimer preparation. This review summarizes recent developments in biobased vitrimers and highlights their preparation methods. The limitations of current biobased vitrimers are also discussed.

Optimizing Performance and Design Simulation of a 100 KW Single Rotor Horizontal Axis Wind Turbine

As wind energy becomes increasingly vital in global energy strategies, optimizing wind turbine design is essential. This research focuses on the development of a 100 kW single rotor horizontal axis wind turbine (HAWT) tailored to meet the energy needs of Jamshoro, Pakistan. The turbine design leverages SolidWorks for structural modeling and is validated through comprehensive simulations using ANSYS and Q-Blade. Operating at an optimal wind speed of 6.9 m/s, the turbine achieves maximum efficiency, as indicated by the highest power factor. This efficiency translates to an estimated power output of approximately 100 kW, suitable for common household consumption. The study integrates regional climatic data and wind conditions to enhance turbine performance and durability. The findings offer a sustainable energy solution for Jamshoro, contributing to Pakistan’s renewable energy infrastructure and addressing local energy demands effectively. The focus of this study will be Jamshoro, a region in Pakistan as a case study. The software simulations will consider a variety of elements, including as wind speeds, variable loads, and environmental factors unique to the chosen region (Jamshoro). This research proposes a sustainable solution for addressing the energy demands in Jamshoro by integrating accurate data based on software analysis with real-world concerns, adding to the larger goal of developing sustainable sources of energy in Pakistan.