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Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~105–107 M−1, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20–29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments. [ABSTRACT FROM AUTHOR]

Renewable biofuels, such as biodiesel, bioethanol, and biobutanol, serve as long-term solutions to fossil fuel depletion. A sustainable approach feedstock for their production is plant biomass, which is degraded to sugars with the aid of microbes-derived enzymes, followed by microbial conversion of those sugars to biofuels. Considering their global demand, additional efforts have been made for their large-scale production, which is ultimately leading breakthrough research in biomass energy. Metagenomics is a powerful tool allowing for functional gene analysis and new enzyme discovery. Thus, the present article summarizes the revolutionary advances of metagenomics in the biofuel industry and enlightens the importance of unexplored habitats for novel gene or enzyme mining. Moreover, it also accentuates metagenomics potentials to explore uncultivable microbiomes as well as enzymes associated with them. [ABSTRACT FROM AUTHOR]

Aim: Fungal biofilms interfere with the wound healing processes. Henceforth, the study aims to fabricate a biomaterial-based nano-scaffold with the dual functionalities of wound healing and antibiofilm activity. Methods: Nanofibers comprising acacia gum, polyvinyl alcohol and inclusion complex of eugenol in β-cyclodextrin (EG-NF) were synthesized using electrospinning. Antibiofilm studies were performed on Candida species, and the wound-healing activity was evaluated through an in vivo excision wound rat model. Results: The EG-NF potentially eradicated the mature biofilm of Candida species and their clinical isolates. Further, EG-NF also enhanced the re-epithelization and speed of wound healing in in vivo rat experiments. Conclusion: The study established the bifunctional applications of eugenol nanofibers as a transdermal substitute with antifungal potency. [ABSTRACT FROM AUTHOR]

Candida tropicalis is an emerging non-albicans Candida species which is pathogenic to the immune-compromised humans, especially in tropical countries, including India. The acquired resistance of Candida species towards antifungal therapies is of major concern. Moreover, limited efficacy and dosage constraint of synthetic drugs have indicated the prerequisite of finding new and natural drugs for treatment. In the present study, we have compared the influence of citral and thymol on C. tropicalis and its biofilm along with expression levels of certain antifungal tolerance genes. The antifungal and anti-biofilm activities of the both were studied using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) reduction assay, field emission scanning electron microscope (FE-SEM) and confocal laser scanning microscope (CLSM) and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. Citral and thymol have damaged the cells with distorted surface and less viability. Quantitative real-time PCR analysis showed augmented expression of the cell membrane biosynthesis genes including ERG11/CYT450 against citral and the cell wall related tolerance genes involving CNB1 against thymol thus, depicting their differential mode of actions. [ABSTRACT FROM AUTHOR]

Simple sequence repeat (SSR) markers are highly efficient for genetic mapping and molecular breeding in crop plants. Chromosomes 7S and 7U of related non-progenitorAegilopsspecies possess superior genetic systems for high grain iron and zinc content. This study was undertaken to conduct a comprehensive analysis of transferability and polymorphism among group-7 anchored SSR markers of bread wheat (Triticum aestivumL.) toAegilopsspecies for wheat improvement. The study revealed 77% transferability of group 7-specific SSR markers of bread wheat to 7U/7S chromosomes ofAegilopsspecies. More than 80% of the 7D specific markers were found to be transferable with a high level of polymorphism. The transferability to 7S and 7U genome suggested higher similarity between bread wheat genome(s) and S genome as compared with U genome ofAegilopsspecies. These polymorphic markers are highly informative, robust and cost-effective for molecular breeding and could be further utilized for identification of introgression/transfer(s) of 7S/7U chromosomal fragments in bread wheat genome through wide hybridization. [ABSTRACT FROM AUTHOR]

PurposeTo transfer the 2S chromosomal fragment(s) ofAegilops kotschyi(2Sk) into the bread wheat genome which could lead to the biofortification of wheat with high grain iron and zinc content. Materials and methodsWheat-Ae. kotschyi2A/2Sksubstitution lines with high grain iron and zinc content were used to transfer the gene/loci for high grain Fe and Zn content into wheat using seed irradiation approach. ResultsBread wheat plants derived from 40 krad-irradiated seeds showed the presence of univalents and multivalents during meiotic metaphase-I. Genomic in situ hybridization analysis of seed irradiation hybrid F2seedlings showed several terminal and interstitial signals indicated the introgression ofAe. kotschyichromosome segments. This proves the efficacy of seed radiation hybrid approach in gene transfer experiments. All the radiation-treated hybrid plants with high grain Fe and Zn content were analyzed with wheat group 2 chromosome-specific polymorphic simple sequence repeat markers to identify the introgression of small alien chromosome fragment(s). ConclusionRadiation-induced hybrids showed more than 65% increase in grain iron and 54% increase in Zn contents with better harvest index than the elite wheat cultivar WL711 indicating effective and compensating translocations of 2Skfragments into wheat genome. [ABSTRACT FROM AUTHOR]

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China's Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency's (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic. [ABSTRACT FROM AUTHOR]

Plastic materials, particularly polyethylene, are the potential source of environmental pollution. In the present study, a fungal strain was isolated from plastic waste dumpsites capable of adhering to high-density polyethylene (HDPE) surface. The fungal strain was identified as Aspergillus niger (ITCC no. 6052). A visible increase in the growth of the fungi was observed on the surface of the polyethylene when cultured in minimal medium at 30°C and 120 rpm, for 1 month. Approximately 3.44% reduction (gravimetrically) in mass and 61% reduction in tensile strength of polyethylene was observed after 1 month of incubation with fungal isolate. Scanning electron microscope analysis showed hyphael penetration and cracks on the surface of polyethylene. A thick network of fungal hyphae forming a biofilm was also observed on the surface of the plastic pieces. The efficient biofilm formation on polyethylene surface by Aspergillus niger (ITCC no. 6052) is attributed to its high cell surface hydrophobicity. This study indicated that Aspergillus niger (ITCC no. 6052) has ability to degrade thermally oxidized polyethylene. [ABSTRACT FROM AUTHOR]

Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus's spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease. [ABSTRACT FROM AUTHOR]

Minimal natural resistance in guar against Alternaria cyamopsidis blight or leaf spots requires the need to develop improved cultivars with high level of resistance. In this study, we report the silencing of AcCHS7 gene with pSilentCHS7-2 and pARTCHS7 constructs in Alternaria pathogen and guar plants of HG 2–20 variety, respectively. The down-regulation of AcCHS7 delays the disease progression in guar by damaging the hyphae, reducing mycelium growth and conidiation in Alternaria. Hence, this study demonstrates the role of host induced post-transcriptional gene silencing of AcCHS7 as an effective approach to increase the guar productivity by developing resistance against Alternaria cyamopsidis. • Alternaria cyamopsidis causes leaf spot disease in guar which results in yield loss. • AcCHS7 silencing reduce sporulation and mycelium growth in Alternaria cyamopsidis. • The disease progression in transgenic guar plants got delayed by 7-8 weeks. • Survival rate of transgenics was 70% compared to wild plants on fungal infection. [ABSTRACT FROM AUTHOR]

The first committed step of the shikimate pathway is catalyzed by a metalloenzyme 3-deoxy- d -arabino-heptulosonate-7-phosphate synthase (DAH7PS), which exhibits vulnerability to the oxidative stress. DAH7PS undergoes inactivation in multiple ways in the presence of redox metal, H 2 O 2 , and superoxide. The molecular mechanism and susceptibility of its inactivation might differ in different organisms and are presently unclear. In the present work, we have cloned, expressed and purified a DAH7PS from Providencia alcalifaciens (PaDAH7PS). The oligomeric state and effect of redox metal treatment on its stability were analyzed through the size exclusion chromatography. The FTIR, MALDI-TOF/TOF-MS studies revealed that methionine residues were modified to methionine sulfoxide in PaDAH7PS. During oxidation, PaDAH7PS is altered into partially folded protein and unfolded states as determined by CD and Fluorescence studies. A significant loss in enzymatic activity of PaDAH7PS was determined and the formation of amorphous aggregates was visualized using AFM imaging and also confirmed by ThT binding based assay. This is the first report where we have shown a hexameric DAH7PS and the methionine residues of PaDAH7PS get oxidize in the presence of oxidative stress. The partially folded and unfolded oligomeric states with high β-content of PaDAH7PS might be the critical precursors for aggregation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Eucalyptol/β-cyclodextrin loaded nanofibers fabricated using electrospinning. • Antibiofilm activity of eucalyptol enhanced due to its encapsulation in nanofibers. • These nanofibers could be used as an antifungal agent in future. Fungal infections pose a serious threat to humankind due to the toxicity of conventional antifungal therapy and continuous emerging incidence of multidrug resistance. Essential oils fascinated researchers because of their broad antimicrobial activity and minimal cytotoxicity. However, hydrophobic, volatile and low water solubility of essential oils hinder their applications in pharmaceutical industries. Therefore, in this study we have loaded eucalyptol/ β-cyclodextrin inclusion complex to gellan/polyvinyl alcohol nanofibers (EPNF) to eradicate Candida albicans and Candida glabrata biofilms. The electrospun nanofibers characterized by various physicochemical techniques and it was observed that EPNF possess highly hydrophilic surface property that facilitate rapid drug release. EPNF inhibited approximately 70% biofilm of C. albicans and C. glabrata. Time kill results depicted that eucalyptol (EPTL) encapsulation in the nanofibers prolonged its antifungal activity than the pure EPTL. Electron microscopy studies revealed that EPNF disrupted the cell surface of Candida. Collectively the current study suggested nanofiber encapsulation enhanced antibiofilm activity of eucalyptol and these nanoscale systems can serve as an alternative therapeutic strategy to treat fungal infections. Further, the developed nanofibrous materials can be applied as cost effective coating agent for biomedical implants. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease with complex pathogenesis and multiple etiological factors. Besides the essential role of autoreactive T cells and constellation of cytokines, the discovery of IL-23/Th17 axis as a central signaling pathway has unraveled the mechanism of accelerated inflammation in psoriasis. This has provided insights into psoriasis pathogenesis and revolutionized the development of effective biological therapies. Moreover, genome-wide association studies have identified several candidate genes and susceptibility loci associated with this disease. Although involvement of cellular innate and adaptive immune responses and dysregulation of immune cells have been implicated in psoriasis initiation and maintenance, there is still a lack of unifying mechanism for understanding the pathogenesis of this disease. Emerging evidence suggests that psoriasis is a high-mortality disease with additional burden of comorbidities, which adversely affects the treatment response and overall quality of life of patients. Furthermore, changing trends of psoriasis-associated comorbidities and shared patterns of genetic susceptibility, risk factors and pathophysiological mechanisms manifest psoriasis as a multifactorial systemic disease. This review highlights the recent progress in understanding the crucial role of different immune cells, proinflammatory cytokines and microRNAs in psoriasis pathogenesis. In addition, we comprehensively discuss the involvement of various complex signaling pathways and their interplay with immune cell markers to comprehend the underlying pathophysiological mechanism, which may lead to exploration of new therapeutic targets and development of novel treatment strategies to reduce the disastrous nature of psoriasis and associated comorbidities. • Psoriasis is a momentous health challenge affecting more than 125 million people globally. • IL-23/Th17 axis provided insights into immunological interactions and cytokines constellation in psoriasis. • Despite the role of immune responses and dysregulated immune cells, psoriasis lacks a unifying mechanism of pathogenesis. • Multifactorial pathophysiology and additional comorbidities present psoriasis as a systemic disease. • Understanding the interplay of complex signaling pathways in psoriasis-related comorbidities is important. [ABSTRACT FROM AUTHOR]

In the present work, new chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method was established and validated for the quantification of pomalidomide (PMD) enantiomers in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm, 5 μm; because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. The mobile phase was maintained as methanol: glacial acetic acid (499.50 ml:50 μL). Ultraviolet wavelength for detection was 220 nm. PMD enantiomer-I and enantiomer-II were separated at 8.83 and 15.34 min, respectively. Limit of detection and limit of quantification for each enantiomer and the calibration curve of standard PMD was linear in range between 10-5,000 ng mL-1. The method was validated according to The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH(Q2R1)) specific guidelines. We found no interference peak with PMD chromatogram obtained. This is a simple, reliable and specific method for detection and quantification of enantiomer of PMD in human plasma sample., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fusarium oxysporum f.sp. lycopersici is a phytopathogen which causes vascular wilt disease in tomato plants. The survival tactics of both pathogens and hosts depend on intricate interactions between host plants and pathogenic microbes. Iron-binding proteins (IBPs) and copper-binding proteins (CBPs) play a crucial role in these interactions by participating in enzyme reactions, virulence, metabolism, and transport processes. We employed high-throughput computational tools at the sequence and structural levels to investigate the IBPs and CBPs of F. oxysporum. A total of 124 IBPs and 37 CBPs were identified in the proteome of Fusarium. The ranking of amino acids based on their affinity for binding with iron is Glu > His> Asp > Asn > Cys, and for copper is His > Asp > Cys respectively. The functional annotation, determination of subcellular localization, and Gene Ontology analysis of these putative IBPs and CBPs have unveiled their potential involvement in a diverse array of cellular and biological processes. Three iron-binding glycosyl hydrolase family proteins, along with four CBPs with carbohydrate-binding domains, have been identified as potential effector candidates. These proteins are distinct from the host Solanum lycopersicum proteome. Moreover, they are known to be located extracellularly and function as enzymes that degrade the host cell wall during pathogen-host interactions. The insights gained from this report on the role of metal ions in plant-pathogen interactions can help develop a better understanding of their fundamental biology and control vascular wilt disease in tomato plants., (© 2024 Wiley Periodicals LLC.)

Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL 1 ), 3-methoxysalicylaldehyde (HL 2 ), 5-bromosalicylaldehyde (HL 3 ), and 3,5-di- tert -butylsalicylaldehyde (HL 4 ) react with [V IV O(acac) 2 ] in MeOH followed by aerial oxidation to give [V V O 2 (L 1 )] ( 1 ), [V V O 2 (L 2 )] ( 2 ), [V V O 2 (L 3 )] ( 3 ), and [V V O 2 (L 4 )] ( 4 ). Complex [V IV O(acac)(L 1 )] ( 5 ) is also isolable from [V IV O(acac) 2 ] and HL 1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H 2 O 2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC 50 = 16 μg/mL, 4 with MIC 50 = 12 μg/mL, and 5 with MIC 50 = 16 μg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis . On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC 50 in the 27.3-33.5 μg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 μg/mL) compared to MCF-7.