Photocatalysis has emerged as a crucial technology for utilizing solar energy to combat global warming and energy shortages. In this realm, both organic and inorganic halide/oxide perovskites have attracted considerable interest. Despite the prevalence of research on lead-based perovskites, the focus is shifting towards lead-free alternatives due to lead's detrimental environmental impact. These materials are at the forefront of developments in photovoltaics, optoelectronics, and photocatalysis. When combined with carbon-based materials to form heterojunctions, lead-free perovskites demonstrate outstanding photocatalytic performance while being cost-effective. This review examines various synthesis methods for lead-free perovskites and their numerous heterojunctions with carbon-based materials. It specifically highlights Z- and S-scheduled heterojunctions, emphasizing their use in hydrogen production, carbon dioxide reduction, and oxygen evolution. The review emphasizes the evolving field of scientific research aimed at solving current energy and environmental issues.

Marine cyanobacteria offer a rich source of varied natural products with both chemical and biological diversity. Oscillatoria salina (O. salina) is a filamentous non-heterocystous marine cyanobacterium from Oscillatoriaceae family. In this investigation, we have unveiled bioactive extracts from O. salina using two distinct solvent systems, revealing significant anticancer properties. Our assessment of the organic and aqueous extracts (MCE and AE) of O. salina demonstrated pronounced antiproliferative and antimetastatic effects. Notably, this study is the first to elucidate the anticancer and anti-metastatic potential of O. salina extracts in both 2D and 3D cell culture models. Both MCE and AE induced apoptosis, hindered cell proliferation, invasion, and migration in A549 non-small cell lung cancer cells, accompanied by alterations in cell morphology and cytoskeleton collapse. Moreover, MCE and AE induced spheroid disintegration in A549 cells. Transcriptomics analysis highlighted the significant involvement of Rap1 and p53 signaling pathways in mediating the observed antitumor effects. Mass spectroscopy characterization of these extracts identified 11 compounds, some known for their anticancer potential. HPLC analysis of AE revealed six peaks with UV absorption spectra resembling phycocyanin, a cyanobacterial pigment with well-known anticancer activity. Collectively, these findings underscore the anticancer potential of MCE and AE, containing bioactive metabolites with anticancer and antimetastatic properties.

Geographical epidemiology has been description of geographical patterns of mortality rates as part of descriptive epidemiological investigations, with the goal of developing theories regarding disease causation. Disease mapping, disease clustering, and ecological analysis are the predominant methods of geographical epidemiology, having close relationships between them. For describing the transmission of an illness within a geographically dispersed population, many models incorporating frameworks based on individuals, networks, stochastic processes, as well as partial derivative equations have been made. However, these models need a large amount of information and even a large amount of computational performance. Keeping this in mind, we have tried to create deterministic models formulated as partial differential equations to model spatial epidemics in spatial domains. This has been by assuming two types of population, the susceptible population, and the infective population, considering the functions of space and time. COVID-19 is a global tragedy, with India likely to be among the most hit. The fluctuation in the dispersion of COVID-19-related well-being results is most likely connected with numerous basic factors, like segment, financial, or natural poisons related factors.

This study presents the synthesis of pristine LaMnO3 (LMO) perovskite nanoparticles (NPs) and LMO/rGO nanocomposites (NCs) incorporating 5, 10, and 20 wt.% of reduced graphene oxide (rGO) through an ultrasonicated sol-gel method. The structural, morphological, and optical properties were determined from X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and UV-Vis spectroscopy. The microstructure and crystallite size of NCs were observed as hexagonal perovskite structures in the 23.4- 20.1 nm range. The specific surface area of LMO NPs and LMO/rGO NCs were observed to be 6.63 m2/g and 21.39 m2/g, respectively. The photocatalytic activity of NCs was estimated to be responsible for methylene blue (MB) degradation under sunlight irradiation. The LMO/rGO10 NC showed the highest photocatalytic degradation with a degradation rate of 0.00927 min-1 and the highest stability due to increased catalytic active sites. The LMO/rGO NCs hold the potential for the photocatalytic degradation of discharged dyes from textile industries under natural sunlight irradiation.

The leaves of Pterocarpus santalinus have been identified as a good source of health-beneficial flavonoids through the amalgamation of untargeted metabolomics using UHPLC-ESI-MSn leading to the identification of flavoneglycosides bearing isorhamnetin and quercetin skeletons. To unveil the optimum ultrasonication extraction conditions required for the comprehensive extraction of major flavone-glycosides, isorhamnetin-3-O-(1-d-(2-Oa-L-rhamnopyranosyl)glucopyranoside and isorhamnetin-3-O-(1-d-glucopyranoside, the response surface methodology based on Box-Behnken design was adopted. The influence of input extraction parameters extraction time (X1): 15-45 min, temperature (X2): 40-60 degrees C and biomass-solvent ratio (X3): 60-100 on the extractive yield and comprehensive flavonoid content resulted in the optimal conditions as 19.09 min, 48.65 oC, and 72.15, respectively. The investigation provides a sustainable approach for recovering health-beneficial flavone-glycosides for utilization in various industries.

In the present work, halloysite nanotubes modified with gold nanoparticles (AuNPs-HNT) are successfully prepared by wet chemical method for the catalytic degradation of phenothiazine dyes (azure B (AZB) and toluidine blue O (TBO)) and also cleaner reduction of 4-(4-nitrophenyl)morpholine (4NM) in the sodium borohydride (NaBH4) media. The catalyst is formulated by modifying the HNT support with a 0.964

Metabolomics is emerging as a promising tool to understand the effect of immunometabolism for the development of novel host-directed alternative therapies. Immunometabolism can modulate both innate and adaptive immunity in response to pathogens and vaccinations. For instance, infections can affect lipid and amino acid metabolism while vaccines can trigger bile acid and carbohydrate pathways. Metabolomics as a vaccinomics tool, can provide a broader picture of vaccine-induced biochemical changes and pave a path to potentiate the vaccine efficacy. Its integration with other systems biology tools or treatment modes can enhance the cure, response rate, and control over the emergence of drug-resistant strains. Mycobacterium tuberculosis (Mtb) infection can remodel the host metabolism for its survival, while there are many biochemical pathways that the host adjusts to combat the infection. Similarly, the anti-TB vaccine, Bacillus Calmette-Guerin (BCG), was also found to affect the host metabolic pathways thus modulating immune responses. In this review, we highlight the metabolomic schema of the anti-TB vaccine and its therapeutic applications. Rewiring of immune metabolism upon BCG vaccination induces different signaling pathways which lead to epigenetic modifications underlying trained immunity. Metabolic pathways such as glycolysis, central carbon metabolism, and cholesterol synthesis play an important role in these aspects of immunity. Trained immunity and its applications are increasing day by day and it can be used to develop the next generation of vaccines to treat various other infections and orphan diseases. Our goal is to provide fresh insight into this direction and connect various dots to develop a conceptual framework.

Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis (TB), employs ten enzymes including imidazoleglycerol-phosphate dehydratase (IGPD) for de novo biosynthesis of histidine. The absence of histidine-biosynthesis in humans combined with its essentiality for Mtb makes the enzymes of this pathway major anti-TB drug targets. We explored the inhibitory potential of a small molecule beta-(1,2,4-Triazole-3-yl)-DL-alanine (DLA) against Mtb IGPD. DLA exhibits an in vitro inhibitory efficacy in the lower micromolar range. Higher-resolution crystal structures of native and substrate-bound Mtb IGPD provided additional structural features of this important drug target. Crystal structure of IGPD-DLA complex at a resolution of 1.75 angstrom, confirmed that DLA locks down the function of the enzyme by binding in the active site pocket of the IGPD mimicking the substrate-binding mode to a high degree. In our biochemical study, DLA showed an efficient inhibition of Mtb IGPD. Furthermore, DLA also showed bactericidal activity against Mtb and Mycobacterium smegmatis and inhibited their growth in respective culture medium. Importantly, owing to the favorable ADME and physicochemical properties, it serves as an important lead molecule for further derivatizations.

Nanopharmaceuticals play a great role in drug delivery as they increase the pharmacokinetic profile of a drug to exert a site-specific effect efficiently. In consideration of the pharmacokinetic parameters solubility of a drug is an important factor to affect the bioavailability. To overcome the solubility issues of drugs, emulsions are one of the effective drug delivery systems wherein the lipophilic and aqueous phases are mixed with the aid of surfactants and co-surfactants to obtain a homogenous system designated as micro or nanoemulsions depending upon the globule size of the dispersed phase. Most of these surfactants in use are synthetic or semi-synthetic having toxic and hazardous effects thus created the demand for safe sustainable plant-based natural surfactants. Saponins, triterpenoid glycosides, possess the characteristics of a typical surfactant by bearing both lipophilic (aliphatic terpenoids unit) and hydrophilic (attached sugars) moieties to stabilize an emulsion. Bearing surfactant like properties, saponins act at the interface of two immiscible phases to reduce surface tension resulting in a uniformly dispersed homogenous system. The current chapter highlights the recent advancement/development of saponins stabilized micro, nanoemulsion, and future application in drug delivery.

This chapter focuses on the area of visible light-based photocatalytic material, and the utilization of efficient solar energy is the main challenge of energy storage and environmental pollution. Owing to their wide bandgap, optical as well as electronic properties transition metal oxide nanoparticles have been significantly facilitating the photocatalysis applications. This chapter describes the progress in the variety of nanometal oxides with their small size, high surface to volume ratio, and better photocatalyst applications under the visible light. The mechanisms involved during the photocatalytic reaction, remediation, and energy generation are also introduced. The charge transfer mechanism was also explained while the other metal oxide nanoparticles were doped in the host metal oxide nanoparticles. A brief outlook of different metal oxide nanoparticle is mentioned in this chapter.

( ), the causative agent of human tuberculosis (TB), employs ten enzymes including imidazoleglycerol-phosphate dehydratase (IGPD) for de novo biosynthesis of histidine. The absence of histidine-biosynthesis in humans combined with its essentiality for makes the enzymes of this pathway major anti-TB drug targets. We explored the inhibitory potential of a small molecule β-(1,2,4-Triazole-3-yl)-DL-alanine (DLA) against IGPD. DLA exhibits an in vitro inhibitory efficacy in the lower micromolar range. Higher-resolution crystal structures of native and substrate-bound IGPD provided additional structural features of this important drug target. Crystal structure of IGPD-DLA complex at a resolution of 1.75 Å, confirmed that DLA locks down the function of the enzyme by binding in the active site pocket of the IGPD mimicking the substrate-binding mode to a high degree. In our biochemical study, DLA showed an efficient inhibition of IGPD. Furthermore, DLA also showed bactericidal activity against and and inhibited their growth in respective culture medium. Importantly, owing to the favorable ADME and physicochemical properties, it serves as an important lead molecule for further derivatizations.

Application of mathematics has gotten progressively abundant in epidemic disease research. The complexity of disease is appropriate to quantitative methodologies as it gives difficulties and chances to new turns of events. Thusly, computational modeling demonstrating to epidemiology research by assisting with clarifying components and by giving quantitative expectations that can be approved. The ongoing extension of quantitative models tends to numerous inquiries with respect to Epidemic disease (COVID-19) inception, and treatment reactions and opposition. These models have allowed researchers to better understand the physical phenomena. Computational models can supplement exploratory and clinical investigations, yet additionally challenge flow standards, reclassify our comprehension of systems driving epidemiology and shape future research. © 2021 Scrivener Publishing LLC.

Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type Mtb evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ-/- mouse model, the auxotroph exhibits a similar extent of virulence as that of the wild-type. The results augment the current understanding of host-Mtb interactions and highlight the essentiality of Mtb histidine biosynthesis for its pathogenesis.

Microbial floras present in crop's vicinity and the soil are close partners of plants in all its developmental stages. These are capable of colonising the rhizosphere and phyllosphere as well as living inside the plant tissues as endophytes. The biodiversity of microbes has been observed with the association of plants from different genera and species. The overburdened population has put enormous pressure on modern agriculture and it has to be more productive, sustainable and environmentally friendly to support the future scenario. The use of beneficial micro-organisms (microbial inoculants) as alternatives to chemical pesticides and synthetic fertilisers in agriculture is needed for sustainable agriculture. The diverse range of activities as well as the number of microbes sorted out in different culture collections around the world may provide an important resource to rationalise the use of chemical fertilisers in agriculture.

Bacteria, fungi, virus and nematode constitute the primary class of pathogens causing plant diseases. Plant–pathogen interactions are crucial for the identification of the host and pathogen and further establishments of a network of interaction that can cross regulate the gene expressions in both sides. After infection, the correct identification of pathogen through various molecular interactions elicit a defense response against the pathogen by alteration of gene expression by the host. Co-evolution of pathogen gives them the ability to counter the virulence response of the host and pathogen can also modulate the host gene expression pattern to make it more susceptible to the infection. Small non-coding RNA molecules (siRNAs and miRNAs) efficiently modulate gene expression at the transcriptional and post-transcriptional level and play a vital role in host defense. The pathogen can also use this double-sided sward in their defense by deregulating the plant immunity via transcriptional control of plant genes utilizing RNA interference or suppressing the host RNA interference response with the help of various RNA silencing suppressor proteins. This mini-review focused on the miRNAs involvement in host defense and how different families of these non-coding regulatory RNAs regulate the defense response against the pathogen.

Bacterioferritins (Bfrs) are ferritin-like molecules with a hollow spherical 24-mer complex design that are unique to bacterial and archaeal species. They play a critical role in storing iron(III) within the complex at concentrations much higher than the feasible solubility limits of iron(III), thus maintaining iron homeostasis within cells. Here, the crystal structure of bacterioferritin from Achromobacter (Ach Bfr) that crystallized serendipitously during a crystallization attempt of an unrelated mycobacterial protein is reported at 1.95 Å resolution. Notably, Fe atoms were bound to the structure along with a porphyrin ring sandwiched between the subunits of a dimer. Furthermore, the dinuclear ferroxidase center of Ach Bfr has only a single iron bound, in contrast to the two Fe atoms in other Bfrs. The structure of Ach Bfr clearly demonstrates the substitution of a glutamate residue, which is involved in the interaction with the second Fe atom, by a threonine and the consequent absence of another Fe atom there. The iron at the dinuclear center has a tetravalent coordination, while a second iron with a hexavalent coordination was found within the porphyrin ring, generating a heme moiety. Achromobacter spp. are known opportunistic pathogens; this structure enhances the current understanding of their iron metabolism and regulation, and importantly will be useful in the design of small-molecule inhibitors against this protein through a structure-guided approach.

The absence of a histidine biosynthesis pathway in humans, coupled with histidine essentiality for survival of the important human pathogen Mycobacterium tuberculosis (Mtb), underscores the importance of the bacterial enzymes of this pathway as major antituberculosis drug targets. However, the identity of the mycobacterial enzyme that functions as the histidinol phosphate phosphatase (HolPase) of this pathway remains to be established. Here, we demonstrate that the enzyme encoded by the Rv3137 gene, belonging to the inositol monophosphatase (IMPase) family, functions as the Mtb HolPase and specifically dephosphorylates histidinol phosphate. The crystal structure of Rv3137 in apo form enabled us to dissect its distinct structural features. Furthermore, the holo-complex structure revealed that a unique cocatalytic multizinc-assisted mode of substrate binding and catalysis is the hallmark of Mtb HolPase. Interestingly, the enzyme-substrate complex structure unveiled that although monomers possess individual catalytic sites they share a common product-exit channel at the dimer interface. Furthermore, target-based screening against HolPase identified several small-molecule inhibitors of this enzyme. Taken together, our study unravels the missing enzyme link in the Mtb histidine biosynthesis pathway, augments our current mechanistic understanding of histidine production in Mtb, and has helped identify potential inhibitors of this bacterial pathway.

High-temperature requirement A (HtrA) proteins, which are members of the heat-shock-induced serine protease family, are involved in extracytoplasmic protein quality control and bacterial survival strategies under stress conditions, and are associated with the virulence of several pathogens; they are therefore major drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1 (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a transmembrane helix and a periplasmic region. Here, the crystal structure of the periplasmic region consisting of a protease domain (PD) and a PDZ domain from an M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 Å resolution. Although the mHtrA1S387A PD shows structural features similar to those of other HtrAs, its loops, particularly L3 and LA, display different conformations. Loop L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a transition from an active to an inactive conformation, as reported for an equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer formation owing to its length (50 amino acids) in DegP, is very short in mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and therefore lacks essential interactions for the formation of higher oligomers. Notably, a well ordered loop known as the insertion clamp in the PDZ domain interacts with the protease domain of the adjacent molecule, which possibly aids in the stabilization of a trimeric functional unit of this enzyme. The three-dimensional structure of mHtrA1S387A presented here will be useful in the design of enzyme-specific antituberculosis inhibitors.

The global tuberculosis (TB) epidemic, caused by the pathogen Mycobacterium tuberculosis (Mtb), is aggravated by the emergence of extremely drug resistant and multi-drug resistant strains. The present situation necessitates the identification and characterization of new drug targets. The histidine (His) biosynthetic pathway (Figure), which converts 5-phosphoribosyl-1-pyrophosphate to histidine in ten enzymatic steps, is essential for Mtb growth but is absent in mammals, thus making it an attractive anti-TB drug target. The enzymes of the His pathway are largely conserved across the bacteria, fungi and lower eukaryotes that synthesize histidine de novo with some differences in a few catalytic steps; particularly the fifth, sixth and eighth steps. The determination of the Mtb genome sequence provided a map of the genes involved in its His pathway. However, it was unclear which particular enzyme catalyzes the eighth step-the dephosphorylation of Histidinol phosphate(HOLP) to Histidinol(HOL). In this study, employing bioinformatic approaches, the Histidinol phosphate phosphatase of Mtb was identified. The target protein was overexpressed in M. smegmatis and purified to homogenity. Its function was established using biochemical assays. The protein was crystallized in native as well as in substrate-bound complex forms and their structures were determined. Residues that line the active site pocket and the residues that are involved in catalysis were determined using both crystal structure and mutational studies data. The biological functional unit of HisN is a dimer, the overall structure of a monomer (260 amino acids) folds into two distinct structural domains, N and C-terminal domains. A loop of 20-residue long connects these two domains. The N-terminal domain consists of residues 2-130. Its tertiary structure comprised of two long alpha helices followed by a six-stranded anti-parallel β-sheet. The C-terminal domain comprised of residues 150-260 and folds into a globular structure consisting a five-stranded anti-parallel β-sheet sandwiched between six α-helices.