Structure of a novel form of phosphopantetheine adenylyltransferase from Klebsiella pneumoniae at 2.59 Å resolution.

Phosphopantetheine adenylyltransferase (EC. 2.7.7.3, PPAT) catalyzes the penultimate step of the multistep reaction in the coenzyme A (CoA) biosynthesis pathway. In this step, an adenylyl group from adenosine triphosphate (ATP) is transferred to 4'-phosphopantetheine (PNS) yielding 3'-dephospho-coenzyme A (dpCoA) and pyrophosphate (PPi). PPAT from strain C3 of Klebsiella pneumoniae (KpPPAT) was cloned, expressed and purified. It was crystallized using 0.1 M HEPES buffer and PEG10000 at pH 7.5. The crystals belonged to tetragonal space group P41212 with cell dimensions of a = b = 72.82 Å and c = 200.37 Å. The structure was determined using the molecular replacement method and refined to values of 0.208 and 0.255 for Rcryst and Rfree factors, respectively. The structure determination showed the presence of three crystallographically independent molecules A, B and C in the asymmetric unit. The molecules A and B are observed in the form of a dimer in the asymmetric unit while molecule C belongs to the second dimer whose partner is related by crystallographic twofold symmetry. The polypeptide chain of KpPPAT folds into a ß/α structure. The conformations of the side chains of several residues in the substrate binding site in KpPPAT are significantly different from those reported in other PPATs. As a result, the modes of binding of substrates, phosphopantetheine (PNS) and adenosine triphosphate (ATP) differ considerably. The binding studies using fluorescence spectroscopy indicated a KD value of 3.45 × 10-4 M for ATP which is significantly lower than the corresponding values reported for PPAT from other species.

Nanobiomaterials: exploring mechanistic roles in combating microbial infections and cancer.

The initiation of the "nanotechnology era" within the past decade has been prominently marked by advancements in biomaterials. This intersection has opened up numerous possibilities for enhancing the detection, diagnosis, and treatment of various illnesses by leveraging the synergy between biomaterials and nanotechnology. The term "nano biomaterials" referring to biomaterials featuring constituent or surface feature sizes below 100 nm, presents a realm of extraordinary materials endowed with unique structures and properties. Beyond addressing common biomedical challenges, these nano biomaterials contribute unprecedented insights and principles that enrich our understanding of biology, medicine, and materials science. A critical evaluation of recent technological progress in employing biomaterials in medicine is essential, along with an exploration of potential future trends. Nanotechnology breakthroughs have yielded novel surfaces, materials, and configurations with notable applications in the biomedical domain. The integration of nanotechnology has already begun to enhance traditional biomedical practices across diverse fields such as tissue engineering, intelligent systems, the utilization of nanocomposites in implant design, controlled release systems, biosensors, and more. This mini review encapsulates insights into biomaterials, encompassing their types, synthesis methods, and the roles of organic and inorganic nanoparticles, elucidating their mechanisms of action. Furthermore, the focus is squarely placed on nano biomaterials and their versatile applications, with a particular emphasis on their roles in anticancer and antimicrobial interventions. This review underscores the dynamic landscape of nanotechnology, envisioning a future where nano biomaterials play a pivotal role in advancing medical applications, particularly in combating cancer and microbial infections.

Exploring the mechanisms and impacts of melatonin on fish colouration.

The pineal hormone melatonin is a multi-functional molecule with a recognized role in pigment aggregation in chromatophores, mediating its actions through binding to subtypes of its specific receptors. Since its discovery, melatonin has been known to be responsible for pigment aggregation towards the cell centre in fishes, including their embryos, as an adaptation to reduced light and thus results in pale body colouration. Diversity exists in the sensitivity of melanophores towards melatonin at interspecies, intraspecific levels, seasons, and amongst chromatophores at different regions of the animal body. In most of the fishes, melatonin leads to their skin paling at night. It is indicated that the melatonin receptors have characteristically maintained to show the same aggregating effects in fishes and other vertebrates in the evolutionary hierarchy. However, besides this aggregatory effect, melatonin is also responsible for pigment dispersion in certain fishes. Here is the demand in our review to explore further the nature of the dispersive behaviour of melatonin through the so-called ß-melatonin receptors. It is clear that the pigment translocations in lower vertebrates under the effect of melatonin are mediated through the melatonin receptors coupled with other hormonal receptors as well. Therefore, being richly supplied with a variety of receptors, chromatophores and melanocytes can be used as in vitro test models for pharmacological applications of known and novel drugs. In this review, we present diverse effects of melatonin on chromatophores of fishes in particular with appropriate implications on most of the recent findings.

Emerging Field of Nanotechnology in Environment.

The art of utilizing and manipulating micro materials have been dated back to antient era. With the advancement in technologies, the state-of-art methods of nano technologies and nano sciences has been employed in various sectors including environment, product designing, food industry, pharmaceuticals industries to way out solve standard problem of mankind. Due to rapid industrialization and the alarming levels of pollution there has been an urgent need to address the environmental and energy issues. Environmental sustainability concerns the global climate change and pollution including air, water, soil. The field of nanotechnology has proven to be a promising field where sensing and remediation, have been dramatically advanced by the use of nanomaterials. This emergent science of surface to mass ratio is the principle theorem for manipulating structure at molecular levels. The review sums up all the advancements in the field of nanotechnology and their recent application in the environment. New opportunities and challenges have also been discussed in detail to understand the use of nanotechnology as problem-to-solution ratio. Graphical abstract: Image depicting the application of nanotechnology in environmental concerns. The combinations of technologies like bioremediations, bioaugmentations with state-of-the-art nanotechnology like carbon nanotubes and Nano capsules to answer the environmental challenges of soil quality, and plant productivity.

Innovative parallel synthesis of 5-nonanone and furfural from lignocellulosic biomass accompanied by deep economic analysis.

An integrated strategy is developed to utilize all three primary components (cellulose, hemicellulose, and lignin) of lignocellulosic biomass for the coproduction of hydrocarbon fuel (5-nonanone) and bio-chemicals (furfural and high purity lignin). After biomass fractionation, (1) 5-nonanone is produced with high yield of 89% using cellulose-derived γ-valerolactone (GVL), which can potentially serve as a platform molecule for the production of liquid hydrocarbon fuels for the transportation sector; (2) furfural, a valuable platform chemical, is produced using hemicellulose; and (3) production of high-purity lignin, which can be used to produce carbon foams or battery anodes. Separation subsystems are designed to effectively recover the solvents for reuse in the conversion processes, which ultimately improves the economic feasibility of the integrated process, resulting in achieving lower minimum selling price (MSP) of $5.47 GGE-1 for 5-nonanone compared to market price. Heat pump is introduced to perform heat integration, which reduces utility requirements more than 85%. Finally, a wide range of techno-economic analysis is performed to highlight the major cost and technological drivers of the integrated process.

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate.

Depression is the major mental illness which causes along with loss of interest in daily life, a feeling of hopelessness, appetite or weight changes, anger and irritability. Due to the hepatic first-pass metabolism, the absolute bioavailability of fluvoxamine (FVM) after oral administration is about 50%. By avoiding the pre-systemic metabolism, nasal delivery would boost bioavailability of FVM. Additionally, the absorption is anticipated to occur more quickly than it would via the oral route because of the existence of microvilli and high vasculature. A nonionic surfactant, cholesterol and an arachidonic acid-carboxymethyl chitosan (AA-CMCS) conjugate were used to develop FVM-loaded novasomes. To investigate the effects of surfactant concentration, AA-CMCS conjugate concentration and stirring speed on the novasomes' characteristics, a Box-Behnken design was used. The dependent variables chosen were zeta potential, polydispersity index and particle size. The AA-CMCS conjugate was confirmed by 1H-NMR and FTIR. Using Design Expert software (version 7; Stat-Ease Inc., Minneapolis, MN, USA), novasomes were further optimized. The chosen optimal formulation (NAC8) was made up of AA-CMCS conjugate, Span 60 and cholesterol. Particle size, zeta potential and PDI values for NAC8 formulation were 101 nm, -35 mV and 0.263, respectively. The NAC8 formulation's DSC and TGA analysis demonstrated that the medication had been uniformly and amorphously distributed throughout the novasomes. The NAC8 formulation showed 99% and 90% FVM release and permeation, respectively, and the novasome adherence time was 24 h. An improved antidepressant effect along with five-fold increase in bioavailability of FVM was observed after trans-nasal administration of NAC8 formulation compared to the reference commercially available Flumin® tablets. FVM-loaded novasomes administered via the nasal route may therefore constitute an advancement in the management of depression.

Comparative genomics and integrated system biology approach unveiled undirected phylogeny patterns, mutational hotspots, functional patterns, and molecule repurposing for monkeypox virus.

Monkeypox is a viral zoonosis with symptoms that are reminiscent of those experienced in previous smallpox cases. The GSAID database (Global Initiative on Sharing Avian Influenza Data) was used to assess 630 genomes of MPXV. The phylogenetic study revealed six primary clades, as well as a smaller percentage in radiating clades. Individual clades that make up various nationalities may have formed as a result of a particular SNP hotspot type that mutated in a specific population. The most significant mutation based on a mutational hotspot analysis was found at G3729A and G5143A. The gene ORF138, which encodes the Ankyrin repeat (ANK) protein, was found to have the most mutations. This protein mediates molecular recognition via protein-protein interactions. It was shown that 243 host proteins interacted with 10 monkeypox proteins identified as the hub proteins E3, SPI2, C5, K7, E8, G6, N2, B14, CRMB, and A41 through 262 direct connections. The interaction with chemokine system-related proteins provides further evidence that the monkeypox virus suppresses human proteins to facilitate its survival against innate immunity. Several FDA-approved molecules were evaluated as possible inhibitors of F13, a significant envelope protein on the membrane of extracellular versions of the virus. A total of 2500 putative ligands were individually docked with the F13 protein. The interaction between the F13 protein and these molecules may help prevent the monkeypox virus from spreading. After being confirmed by experiments, these putative inhibitors could have an impact on the activity of these proteins and be used in monkeypox treatments.

Fabrication, Characterization and Biomedical Evaluation of a Statistically Optimized Gelatin Scaffold Enriched with Co-Drugs Loaded into Controlled-Release Silica Nanoparticles.

The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (-16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against Candida albicans, the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients' adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.

Therapeutic Benefits of Melatonin against COVID-19.

The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the patients' conditions. Higher melatonin titers in children may provide a protective shield against this disease. The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1ß, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. Nevertheless, within the setting of a clinical intervention, the promising compounds must go through a series of studies before their recommendation. In the clinical field, this is done in a time-ordered sequence, in line with the phase label affixed to proper protocol of trials: phase I-phase II and the final phase III. Nevertheless, while medical recommendations can only be made on the basis of reassuring evidence, there are still three issues worth considering before implementation: representativeness, validity, and lastly generalizability.

Aryl fluorosulfates: powerful and versatile partners in cross-coupling reactions.

Aryl fluorosulfates are versatile building blocks in organic synthesis and have gained increasing attention in SuFEx (Sulfur Fluoride Exchange) click chemistry. They are easily and conveniently prepared from phenols using sulfuryl fluoride SO2F2 as a low-cost sulfonyl fluoride provider. Recently, they served as less toxic and more atom economical alternatives to triflates in an impressive number of carbon-carbon and carbon-heteroatom cross-coupling reactions. In this review, we summarize the current advances and developments in applying aryl fluorosulfates as electrophilic partners in cross-coupling reactions.

Nano-Conversion of Ineffective Cephalosporins into Potent One against Resistant Clinical Uro-Pathogens via Gold Nanoparticles.

Infections caused by resistant bacterial pathogens have increased the complications of clinicians worldwide. The quest for effective antibacterial agents against resistant pathogens has prompted researchers to develop new classes of antibiotics. Unfortunately, pathogens have acted more smartly by developing resistance to even the newest class of antibiotics with time. The culture sensitivity analysis of the clinical samples revealed that pathogens are gaining resistance toward the new generations of cephalosporins at a very fast rate globally. The current study developed gold nanoparticles (AuNPs) that could efficiently deliver the 2nd (cefotetan-CT) and 3rd (cefixime-CX) generation cephalosporins to resistant clinical pathogens. In fact, both CT and CX were used to reduce and stabilize AuNPs by applying a one-pot synthesis approach, and their characterization was performed via spectrophotometry, dynamic light scattering and electron microscopy. Moreover, the synthesized AuNPs were tested against uro-pathogenic resistant clinical strains of Escherichia coli and Klebsiella pneumoniae. CT-AuNPs characteristic SPR peak was observed at 542 nm, and CX-AuNPs showed the same at 522 nm. The stability measurement showed ζ potential as -24.9 mV and -25.2 mV for CT-AuNPs and CX-AuNPs, respectively. Scanning electron microscopy revealed the spherical shape of both the AuNPs, whereas, the size by transmission electron microscopy for CT-AuNPs and CX-AuNPs were estimated to be 45 ± 19 nm and 35 ± 17 nm, respectively. Importantly, once loaded onto AuNPs, both the cephalosporin antibiotics become extremely potent against the resistant strains of E. coli and K. pneumoniae with MIC50 in the range of 0.5 to 0.8 µg/mL. The findings propose that old-generation unresponsive antibiotics could be revived into potent nano-antibiotics via AuNPs. Thus, investing efforts, intellect, time and funds for a nano-antibiotic strategy might be a better approach to overcome resistance than investing the same in the development of newer antibiotic molecule(s).

What Factors Will Influence Chinese International Traveling for Leisure in the Post-COVID-19 Era: Role of Health Priorities and Health-Related Information Literacy.

China used to be the world's leading nation in terms of international (outward) tourism till the COVID-19 outbreak. However, due to the COVID-19 crisis, several new macro and micro-level factors might affect their international (outward) traveling behavior. The purpose of the current research was to examine the avoidance of international traveling for leisure in the Chinese population. The goal of the study was to highlight the importance of information self-efficacy and digital literacy as the key factors influencing tourists' traveling readiness. To achieve the goal, the study adapted the quantitative instruments from existing sources to map media exhaustion, information overload, and perceived health concerns, i.e., perceived effectiveness of health-protective measures, fear of new possible outbreaks, and pandemic crisis at source and destination. Chinese citizens' opinions were collected during the third quarter of the year 2022. Specifically, the quantitative survey from China collected a total number of 1308 respondents. This study used the statistical analysis software SPSS to analyze collected data. The findings conclude that the role of media is pivotal to shaping and predicting future trends in tourism preferences, perception of protective measures against COVID-19, and perceived seriousness of the pandemic crisis in the Chinese population. In addition, technology readiness (as hard self-efficacy) and health-related information literacy (soft self-efficacy) are critical to cope with the dark aspects of information exhaustion, overload, and pandemic seriousness in the post-truth era. The study is unique, as it examines the role of the seriousness of the pandemic at its source and destination and fear of new outbreaks simultaneously, underlining the potential future of immersive tourism (i.e., virtual reality, augmented reality, or mixed reality-based tourism). This study has drawn interesting theoretical and practical implications for researchers, policymakers, and academicians.

Porous Ag3VO4/KIT-6 composite: Synthesis, characterization and enhanced photocatalytic performance for degradation of Congo Red.

Novel Ag3VO4/KIT-6 nanocomposite photocatalyst has been successfully fabricated by a newly-designed simple hard-template induction process, in which the particles of Ag3VO4 were grown on the KIT-6 surface and inside the porous framework of the silica matrix. The developed porous framework nanocomposite was characterized by several techniques including N2-Physiosorption analysis. The obtained nanocomposite revealed a high surface area (273.86 m2/g) along with the possession of monoclinic Ag3VO4, which is highly responsive to visible light (with distinct intensity at about 700 nm). The UV-Vis DRS reveals that the Ag3VO4/KIT-6 photocatalyst bears a bandgap of 2.29 eV which confirms that the material has a good visible light response. The synthesized nanocomposite was tested for its superior physicochemical properties by evaluating its degradation efficiency for Congo Red (CR). The novel composite exhibited superior degradation capability of CR, reaching up to 96.49%, which was around three times the pure Ag3VO4. The detailed kinetic study revealed that the as-prepared material followed a pseudo first order kinetic model for the CR degradation. The study includes a comprehensive parametric study for the formulation of the optimized reaction conditions for photocatalytic reactions. The commercial applicability of the composite material was investigated by a regeneration and recyclability test, which revealed extraordinary results. Furthermore, the possible degradation pathway for CR was also proposed.

An exclusive review of melatonin effects on mammalian melanocytes and melanoma.

Melatonin influences mammalian coat colour and hair follicle pigmentation and also weakly alters the electrical stimulation of retinal cells in the eyes. A direct melanocytic response to melatonin is still uncertain in mammals and human skin pigmentation. Melatonin acts as a free radical scavenger and thus inhibits the initiation of cancer cell growth. Treatment of melanoma sees perspective features in the administration of melatonin along with known chemotherapeutic molecules to improve the efficacy of conventional cytotoxic agents. Being richly supplied with a variety of receptors, melanocytes and melanoma cells can be used as in vitro test models for pharmacological applications of known and novel drugs.

Acute Limb Ischemia Caused by Dissection following Percutaneous Coronary Intervention Using Right Radial Approach.

Iatrogenic aortic dissection is a rare but potentially fatal complication of percutaneous coronary intervention (PCI). Iatrogenic aortic dissection following PCI is rare with most cases reporting dissection originating within the coronary vessels with propagation into the ascending aorta. In this specific case, dissection was without coronary involvement, with dissection extending from the ascending aorta into the descending aorta and iliac vessels. Although PCI via radial approach is associated with fewer vascular complications than with femoral approach, significant adverse outcomes may still occur and require prompt intervention. This case highlights the highly atypical presentation of iatrogenic aortic dissection following cardiac catheterization presenting as acute limb ischemia. In such patients as with ours, immediate surgical intervention is necessary with overall poor prognosis.

Development and Applications of Embedded Passives and Interconnects Employing Nanomaterials.

The advent of nanotechnology has initiated a profound revolution in almost all spheres of technology. The electronics industry is concerned with the ongoing miniaturization of devices and as such requires packaging technologies that will make the devices more compact and resilient. 3D packaging, system in package, and system on chip are the various packaging techniques that utilize nanoscale components for their implementation. The active components of the ICs have kept pace with Moore's law, but the passive components have proven an impediment in the race for miniaturization. Moreover, the toxic effects and nano-scale problems associated with conventional soldering techniques have entailed the active involvement of nanotechnology in the search for answers. Recent advances in these fields and the diverse nanomaterials which are being employed to resolve these issues have been discussed in detail.

Ligand recognition by peptidoglycan recognition protein-S (PGRP-S): structure of the complex of camel PGRP-S with heptanoic acid at 2.15 Å resolution.

Peptidoglycan recognition proteins (PGRPs) are important components of the innate immune system which provide the first line of defense against invading microbes. There are four members in the family of PGRPs in animals of which PGRP-S is a common domain. It is responsible for the binding to microbial cell wall molecules. In order to understand the mode of binding of PGRP-S to the components of the bacterial cell wall, the structure of the complex of camel PGRP-S (CPGRP-S) with heptanoic acid has been determined at 2.15 Å resolution. The structure determination showed the presence of four crystallographically independent protein molecules which are designated as A, B, C, and D. These four protein molecules associate in the form of two homodimers which are represented as A-B and C-D dimers. The association between molecules A and B gives rise to a shallow cleft on the surface at one end of the dimeric interface. One molecule of heptanoic acid is observed at this binding site in the A-B dimer. The association of C and D molecules results in the formation of a long zig-zag tunnel along with the C-D interface. In the cleft at the C-D interface, three molecules of hydrogen peroxide along with other non-water solvent molecules have been observed. The analysis of the several complexes of CPGRP-S with fatty acids and non-fatty acids such as peptidoglycan, lipopolysaccharide, and lipoteichoic acid shows that the fatty acids bind at the A-B site while non-fatty acids interact through C-D interface.

Simulation and Modelling of Hydrogen Production from Waste Plastics: Technoeconomic Analysis.

The global energy demand is expected to increase by 30% within the next two decades. Plastic thermochemical recycling is a potential alternative to meet this tremendous demand because of its availability and high heating value. Polypropylene (PP) and polyethylene (PE) are considered in this study because of their substantial worldwide availability in the category of plastic wastes. Two cases were modeled to produce hydrogen from the waste plastics using Aspen Plus®. Case 1 is the base design containing three main processes (plastic gasification, syngas conversion, and acid gas removal), where the results were validated with the literature. On the other hand, case 2 integrates the plastic gasification with steam methane reforming (SMR) to enhance the overall hydrogen production. The two cases were then analyzed in terms of syngas heating values, hydrogen production rates, energy efficiency, greenhouse gas emissions, and process economics. The results reveal that case 2 produces 5.6% more hydrogen than case 1. The overall process efficiency was enhanced by 4.13%. Case 2 reduces the CO2 specific emissions by 4.0% and lowers the hydrogen production cost by 29%. This substantial reduction in the H2 production cost confirms the dominance of the integrated model over the standalone plastic gasification model.