Search Results (83)

In this work, we described the synthesis of 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate by reacting 5-bromofuroic acid with methylparaben in the incorporation of DCC/DMAP (Steglich esterification) as coupling agents. Later on, we subsequently synthesized a series of 4-(methoxycarbonyl)phenyl 5-aryl furan-2-carboxylates (5a–5e) through Suzuki coupling catalyzed by palladium (0) between 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate (3) with several substituted arylated and heteroaryl boronic acids (4). DFT calculations were computed to elucidate electronic structural features of synthesized molecules (5a–5e) and to validate these findings by correlating with theoretical and experimental spectroscopic analysis. Furthermore, geometrical optimization, thermodynamic features, as FMO orbitals, MESP maps, NLO behavior and reactivity descriptors, were also determined from the PBE0 D3BJ/def2-TZVP/SMD_1,4-dioxane theory level to confirm the structural features of synthesized molecules. Full article

Patients with advanced melanoma who progress on standard-dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Studies support a dose–response activity of Ipi, and one promising combination is Ipi 10 mg/kg (Ipi10) + temozolomide (TMZ). We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10 + TMZ in the immunotherapy refractory/resistant setting (n = 6, all progressed after prior Ipi + nivolumab), using similar patients treated with Ipi3 + TMZ (n = 6) as comparison. Molecular profiling by whole-exome sequencing (WES) and RNA-sequencing (RNA-seq) of tumors harvested through one responder’s treatment was performed. With a median follow up of 119 days, patients treated with Ipi10 + TMZ had a statistically significant longer median progression-free survival of 144.5 days (range 27–219) vs. 44 (26–75) in Ipi 3 mg/kg (Ipi3) + TMZ, p = 0.04, and a trend of longer median overall survival of 154.5 days (27–537) vs. 89.5 (26–548). Two patients in the Ipi10 + TMZ cohort had a partial response, and both responders had BRAF V600E mutant melanoma. RNA-seq showed enrichment of inflammatory signatures, including interferon responses in metastases after Ipi10 + TMZ compared to the primary tumor, and downregulated negative immune regulators. Ipi10 + TMZ demonstrated efficacy, including dramatic responses in patients refractory to prior Ipi + anti-PD1. Molecular data suggest a potential threshold of Ipi dose for activation of sufficient anti-tumor immune response, and higher doses are required for some patients. Full article

The Citrus clementina (citrus) plant produces various phytohormones due to the significant involvement of the carotenoid cleavage oxygenase (CCO) gene family in its growth and development. CCO genes can be divided into two main categories: NCED (9-cis-epoxy carotenoid dioxygenase), responsible for abscisic acid (ABA) production, and CCD (carotenoid cleavage dioxygenase), involved in pigment and strigolactone formation. To better understand the roles and positions of CcCCO gene members in relation to these hormones, researchers analyzed the clementine genome. To identify their structural features, they employed phylogenetic analysis, protein interactions, localization, structure, miRNA targets, evolutionary analysis, and transcriptome studies. The study revealed the presence of 15 CcCCO genes, including 11 NCED and 4 CCD genes, scattered across various chromosomes, with the majority located in chloroplasts. Promoter sequencing analysis indicated the presence of different cis-regulatory elements that likely interacted with phytohormones, such as auxin and abscisic acid among others. Notably, two genes, CcNCED1 and CcNCED3, were significantly expressed among the CCO genes, and these were found to be expressed during stress and played a crucial role in enabling optimal plant development. Furthermore, a comprehensive genome-wide comparison of CCO genes in C. Clementine and Arabidopsis thaliana models was conducted to understand their functional characteristics. This research provides a solid foundation for further exploration of the unique attributes of the C. clementina plant, contributing to a deeper understanding of its growth and development processes. Full article

In the field of piezoelectric applications, perovskite-based multifunctional composite ceramics are widely explored. The morphotropic phase boundary (MPB) regions, where dual structural phases coexist, play a crucial role in boosting the ferroelectric and piezoelectric properties significantly. Herein, MPB-region-existent 0.7BiFeO₃-0.3BaTiO₃ (BFBT) composite ceramic is investigated under the influence of wt%Sn-ion incorporation at the lattice sites of the BFBT. Specifically, the ceramic composition BFBT:0.2Sn has demonstrated excellent remnant polarization (P_r ~ 22.68 µC/cm²), an impressive piezoelectric coefficient (d₃₃ ~ 211 pC/N), stable impedance of 1.07 × 10⁷ Ω, a Curie temperature of 435 °C and low dielectric loss (tanδ) of <0.5. Moreover, the BFBT:0.2Sn ceramic has also maintained a stable d₃₃ of ~150 pC/N and resistivity of ~10² Ω even at a temperature of 400 °C. Such outcomes confirm the ability and potential of the BFBT:0.2Sn ceramic composition for high-temperature piezoelectric applications. Full article

The demand for developing novel antimicrobial drugs has increased due to the rapid appearance and global spread of antibiotic resistance. Antimicrobial peptides (AMPs) offer distinct advantages over traditional antibiotics, such as broad-range efficacy, a delayed evolution of resistance, and the capacity to enhance human immunity. AMPs are being developed as potential medicines, and current computational and experimental tools aim to facilitate their preclinical and clinical development. Structural and functional constraints as well as a more stringent regulatory framework have impeded clinical translation of AMPs as possible therapeutic agents. Although around four thousand AMPs have been identified so far, there are some limitations of using these AMPs in clinical trials due to their safety in the host and sometimes limitations in the biosynthesis or chemical synthesis of some AMPs. Overcoming these obstacles may help to open a new era of AMPs to combat superbugs without using synthetic antibiotics. This review describes the classification, mechanisms of action and immune modulation, advantages, difficulties, and opportunities of using AMPs against multidrug-resistant pathogens and highlights the need and priorities for creating targeted development strategies that take into account the most cutting-edge tools currently available. It also describes the barriers to using these AMPs in clinical trials. Full article

The palm oil industry (POI) generates significant amounts of waste, including calcium carbonate (CaCO₃) from the clay bath system used for the separation of palm kernels from shells. This CaCO₃ waste is often discarded, leading to environmental issues. However, the CaCO₃ can potentially be reused in the clay bath separation process to improve efficiency and reduce waste. To obtain PKO, the kernel is separated from the palm shell using a clay bath unit, where natural CaCO₃ acts as a decanting agent and adsorbent. This wet separation method, involving a mixture of water and CaCO₃ with a density of 1.12 g/mL, generates substantial amounts of saturated CaCO₃ waste that is often discarded into the environment. Therefore, this research aimed to regenerate oil-bound CaCO₃ waste for reuse as a decanter and adsorbent. Three treatments were tested, with CaCO₃ waste-to-water ratios of 1:1, 1:3, and 1:6, under varying pH levels (8, 10, 11, 12) and temperatures (28 °C, 80 °C, 100 °C). The regeneration process was conducted in an open reactor at 450 rpm with a volume of 0.0054 m³, followed by drying and grinding the waste for analysis. The results showed approximately 75.75% oil removal and CaCO₃ regeneration rates between 94.50% and 99.26%, with an increase in density from 1.687 g/mL to 2.467 g/mL. The efficiency of reusing regenerated CaCO₃ waste is 96.87%. When mixed with 25% natural CaCO₃, the efficiency increases to 99.24%. Additionally, a mixture of 50% regenerated CaCO₃ waste and 50% natural CaCO₃ achieves an average efficiency of 99.46% over five consecutive feed additions. This showed that the reuse of CaCO₃ waste regeneration results for the separation of palm shells and kernels has a high potential for application. These findings suggest that regenerated CaCO₃ waste can be effectively reused, offering a sustainable solution for palm oil mills. Full article

Ensuring global food security amid mounting challenges, such as population growth, disease infestations, resource limitations, and climate change, is a pressing concern. Anticipated increases in food demand add further complexity to this critical issue. Plant pathogens, responsible for substantial crop losses (up to 41%) in major crops like wheat, rice, maize, soybean, and potato, exacerbate the situation. Timely disease detection is crucial, yet current practices often identify diseases at advanced stages, leading to severe infestations. To address this, remote sensing and Hyperspectral imaging (HSI) have emerged as robust and nondestructive techniques, exhibiting promising results in early disease identification. Integrating machine learning algorithms with image data sets enables precise spatial–temporal disease identification, facilitating timely detection, predictive modeling, and effective disease management without compromising fitness or climate adaptability. By harnessing these cutting-edge technologies and data-driven decision-making, growers can optimize input costs while achieving enhanced yields, making significant strides toward global food security in the face of climate change risks. This review will discuss some of the foundational concepts of remote sensing, several platforms used for remote sensing data collection, successful application of the approach, and its future perspective. Full article

Hydrogen production is one of the best solutions to the growing energy concerns, owing to its clean and sustainable assets. The current review gives an overview of various hydrogen production technologies, highlighting solar water splitting as a promising approach for its sustainable production. Moreover, it gives a detailed mechanism of the water-splitting reaction and describes the significance of titania-based catalysts for solar water splitting. It further highlights diversified strategies to improve the catalytic efficiency of TiO₂ for the enhanced hydrogen production. These strategies include the doping of TiO₂, dye sensitization, and the addition of co-catalysts. Doping reduces the bandgap by generating new energy levels in TiO₂ and encourages visible-light absorption. Sensitization with dyes tunes the electronic states, which in turn broadens the light-absorption capacity of titania. Constructing heterojunctions reduces the charge recombination of TiO₂, while co-catalysts increase the number of active sites for an enhanced reaction rate. Thus, every modification strategy has a positive impact on the stability and photocatalytic efficiency of TiO₂ for improved water splitting. Lastly, this review provides a comprehensive description and future outlook for developing efficient catalysts to enhance the hydrogen production rate, thereby fulfilling the energy needs of the industrial sector. Full article

Agriculture plays a fundamental role in ensuring global food security, yet plant diseases remain a significant threat to crop production. Traditional methods to manage plant diseases have been extensively used, but they face significant drawbacks, such as environmental pollution, health risks and pathogen resistance. Similarly, biopesticides are eco-friendly, but are limited by their specificity and stability issues. This has led to the exploration of novel biotechnological approaches, such as the development of synthetic proteins, which aim to mitigate these drawbacks by offering more targeted and sustainable solutions. Similarly, recent advances in genome editing techniques—such as meganucleases (MegNs), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)—are precise approaches in disease management, but are limited by technical challenges and regulatory concerns. In this realm, nanotechnology has emerged as a promising frontier that offers novel solutions for plant disease management. This review examines the role of nanoparticles (NPs), including organic NPs, inorganic NPs, polymeric NPs and carbon NPs, in enhancing disease resistance and improving pesticide delivery, and gives an overview of the current state of nanotechnology in managing plant diseases, including its advantages, practical applications and obstacles that must be overcome to fully harness its potential. By understanding these aspects, we can better appreciate the transformative impact of nanotechnology on modern agriculture and can develop sustainable and effective strategies to mitigate plant diseases, ensuring enhanced agricultural productivity. Full article

Polylactide materials present a promising alternative to petroleum-based polymers due to their sustainability and biodegradability, although they have certain limitations in physical and mechanical properties for specific applications. The incorporation of nanoparticles, such as layered silicate (clay), carbon nanotubes, metal or metal oxide, cellulose nanowhiskers, can address these limitations by enhancing the thermal, mechanicals, barriers, and some other properties of polylactide. However, the distinct characteristics of these nanoparticles can affect the compatibility and processing of polylactide blends. In the polylactide nanocomposites, well-dispersed nanoparticles within the polylactide matrix result in excellent mechanical and thermal properties of the materials. Surface modification is required to improve compatibility and the crystallization process in the blended materials. This article reviews the development of polylactide nanocomposites and their applications. It discusses the general aspect of polylactides and nanomaterials as nanofillers, followed by the discussion of the processing and characterization of polylactide nanocomposites, including their applications. The final section summarizes and discusses the future challenges of polylactide nanocomposites concerning the future material’s requirements and economic considerations. As eco-friendly materials, polylactide nanocomposites offer significant potential to replace petroleum-based polymers. Full article

This study reports a novel CuSe-TiO₂-GO composite, synthesized by a facile hydrothermal method at a controlled temperature, and investigates its electrochemical performance for supercapacitors (SCs) and photocatalytic behavior for degrading methylene blue (MB) dye. The compositional phase structure and chemical bond interaction were thoroughly investigated. The as-fabricated pristine, binary, and ternary composites underwent comprehensive characterization employing spectroscopic techniques and electrochemical analysis. Compared with pure and binary compounds (CuSe, TiO₂, and binary CuSe-TiO₂ composites), the ternary CuSe-TiO₂-GO composites demonstrated a high degradation efficiency while degrading MB in less than just 80 min (240 min, 100 min, and 140 min, respectively). The photocatalytic activity of the ternary CuSe-TiO₂-GO composites is enhanced due to the highly positive conduction band of CuSe, leading to the quick excitation of electrons to the conduction band of CuSe. Subsequently, graphene oxide (GO) left holes on the photocatalyst surface for MB, as GO assisted the photoexcited electron–hole pairs, resulting in enhanced photocatalytic performance. The CuSe-TiO₂-GO electrode for the supercapacitor indicates a 310.6 F/g and 135.2 F/g capacitance when the discharge current upsurges from 1 to 12 A/g. The good photocatalytic and energy storage performance is due to the smaller charge transfer resistance, which promotes efficient separation of electron–hole pairs. Full article

Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant. Full article

Water contamination with synthetic dyes is an escalating problem worldwide. Herein, Co₃O₄-decorated reduced graphene oxide (Co₃O₄-rGO) is reported as an effective heterogeneous photocatalyst for the decomposition of organic dyes. The synthesis of Co₃O₄-rGO was confirmed via spectroscopic techniques including XRD, XPS, TEM, and FTIR. After characterization, the prepared Co₃O₄-rGO composite was tested as a photocatalyst for the degradation of methylene blue and methyl orange. The photocatalytic efficiency of Co₃O₄-rGO was >95% after 60 min, corresponding to 200 mg/L as the initial concentration of each dye. The photodegradation of MB and MO was confirmed by BOD and COD measurements. Experimental parameters like the re-usability of Co₃O₄-rGO, the effect of catalyst dosage, and the effect of dye concentration on photocatalytic activity were also investigated. The photocatalytic activity of Co₃O₄-rGO for the degradation of MB was 2.13 and 3.43 times higher than that of Co₃O₄ and rGO, respectively. Similarly, the photocatalytic activity of Co₃O₄-rGO for the degradation of MO was 2.36 and 3.56 times higher than that of Co₃O₄ and rGO, respectively. Hence, Co₃O₄-rGO was found to be an efficient and reusable photocatalyst for the decomposition of selected dyes in the aqueous medium. Full article

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4’s genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4’s connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4’s carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy. Full article

This study reports the interfacial phenomenon of cefotaxime in combination with nonionic surfactants, Triton X-100 (TX-100) and Tween-80 (TW-80), and their mixed micellar formulations. Cefotaxime was enclosed in a micellar system to improve its solubility and effectiveness. TX-100 and TW-80 were used in an amphiphilic self-assembly process to create the micellar formulation. The effect of the addition of TX-100, a nonionic surfactant, on the ability of TW-80 to solubilize the drug was examined. The values of the critical micelle concentration (CMC) were determined via UV-Visible spectroscopy. Gibbs free energies (ΔG_p and ΔG_b), the partition coefficient (K_x), and the binding constant (K_b) were also computed. In a single micellar system, the partition coefficient (K_x) was found to be 33.78 × 10⁶ and 2.78 × 10⁶ in the presence of TX-100 and TW-80, respectively. In a mixed micellar system, the value of the partition coefficient for the CEF/TW-80 system is maximum (5.48 × 10⁶) in the presence of 0.0019 mM of TX-100, which shows that TX-100 significantly enhances the solubilizing power of micelles. It has been demonstrated that these surfactants are effective in enhancing the solubility and bioavailability of therapeutic compounds. This study elaborates on the physicochemical characteristics and solubilization of reactive drugs in single and mixed micellar media. This investigation, conducted in the presence of surfactants, shows a large contribution to the binding process via both hydrogen bonding and hydrophobic interactions. Full article