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Abstract Influenza D virus (IDV), the cattle flu virus, is a novel multi-host RNA virus, circulating silently worldwide, with widespread seropositivity among US cattle, reaching up to 80% in some areas raising a potential threat of cattle-to-human transmission. Currently, five genetic lineages of IDV have been described, but their evolutionary dynamics have not been studied. Although IDV was first identified in 2011, our comprehensive analysis of all known IDV genomes suggests that the earliest ancestors of IDV likely to have evolved towards the end of the 20th century and D/OK lineage appears to have emerged in 2005. We confirmed a significantly higher substitution rate in IDV than in Influenza C virus, which is consistent with their global distribution and multi-host tropism. We identified multiple sub-populations within the D/OK lineage, highlighting extensive diversification and dissemination. Other findings are evidence for potential reassortment among IDV strains in the USA and transboundary circulation of IDV in Europe with introductions into Danish cattle, some of which potentially originated from France. IDV, an emerging virus with a higher rate of evolution and uncontrolled circulation, could facilitate its adaptation to humans. Our findings underscore the importance of targeted surveillance for IDV in humans and at-risk animal populations.

Abstract Nearly 60 million people worldwide are infected with Hepatitis C Virus (HCV), a bloodborne pathogen which leads to liver cirrhosis and increases the risk of hepatocellular carcinoma. Those with limited access to healthcare resources, such as injection drug users and people in low- and middle-income countries, carry the highest burden. The current diagnostic algorithm for HCV is slow and costly, leading to a significant barrier in diagnosis and treatment for those most at risk from HCV. There remains no available vaccine for HCV, and infection is often asymptomatic until significant cirrhosis has occurred, which makes screening incredibly important to prevent liver damage and transmission. Recent investigation has sought to address these issues through improvements in various aspects of the diagnostic procedure, using methods such as isothermal amplification techniques for viral RNA amplification, the use of viral protein as an analyte, and the incorporation of streamlined, self-contained testing systems to reduce administrative skill requirements. This review provides a comprehensive overview of current commercial standards and novel improvements in HCV diagnostics, as well as a framework for future integration of these improvements to develop a one-step diagnostic that meets the needs of those most affected. Graphical Abstract

Abstract Long intergenic non-coding RNAs (lincRNAs) are emerging as regulators of protein-coding genes (PCGs) in many plant and animal developmental processes and stress responses. In this study, we characterize the genome-wide lincRNAs in potatoes responsive to a vascular bacterial disease presumably caused by Candidatus Liberibacter solanacearum (CLso). Approximately 4397 lincRNAs were detected in healthy and infected potato plants at various stages of zebra chip (ZC) disease progression. Of them, ~65% (2844) were novel lincRNAs, and less than 1% (9) were orthologs of Arabidopsis and rice based on reciprocal BLAST analysis, suggesting species-specific expansion. Among the proximal lincRNAs within 50 kbp from a PCG, ~49% were transcribed from the same strand, while ~39% and ~15% followed convergent (head-to-head) and divergent (tail-to-tail) orientations, respectively. Approximately 30% (1308) were differentially expressed following CLso infection, with substantial changes occurring 21 days after infection (DAI). Weighted Gene Co-expression Network Analysis (WGCNA) of lincRNAs and PCGs identified 46 highly correlated lincRNA–PCG pairs exhibiting co-up or co-downregulation. Furthermore, overexpression of selected lincRNAs in transgenic potato hairy roots resulted in perturbation of neighboring PCG expression and conferred tolerance to CLso infection. Our results provide novel insights into potato lincRNAs’ identity, expression dynamics, and functional relevance to CLso infection.

Acute respiratory distress syndrome (ARDS) is a critical, life-threatening condition marked by severe inflammation and impaired lung function. Mesenchymal stromal/stem cells (MSCs) present a promising therapeutic avenue due to their immunomodulatory, anti-inflammatory, and regenerative capabilities. This review comprehensively evaluates MSC-based strategies for ARDS treatment, including direct administration, tissue engineering, extracellular vesicles (EVs), nanoparticles, natural products, artificial intelligence (AI), gene modification, and MSC preconditioning. Direct MSC administration has demonstrated therapeutic potential but necessitates optimization to overcome challenges related to effective cell delivery, homing, and integration into damaged lung tissue. Tissue engineering methods, such as 3D-printed scaffolds and MSC sheets, enhance MSC survival and functionality within lung tissue. EVs and MSC-derived nanoparticles offer scalable and safer alternatives to cell-based therapies. Likewise, natural products and bioactive compounds derived from plants can augment MSC function and resilience, offering complementary strategies to enhance therapeutic outcomes. In addition, AI technologies could aid in optimizing MSC delivery and dosing, and gene editing tools like CRISPR/Cas9 allow precise modification of MSCs to enhance their therapeutic properties and target specific ARDS mechanisms. Preconditioning MSCs with hypoxia, growth factors, or pharmacological agents further enhances their therapeutic potential. While MSC therapies hold significant promise for ARDS, extensive research and clinical trials are essential to determine optimal protocols and ensure long-term safety and effectiveness.

The aim of the present study was to make a polyherbal formulation of three herbs that would offset the negative effects of the high-fat cafeteria diet on rats and the beneficial effects of exercise. The ingredients for this herbal remedy included a water extract of Garcinia cambogia fruit, Trigonella foenum-graecum seed, and Glycyrrhiza glabra root in a 1:1:1 ratio. Nine groups of six male Wistar albino rats were chosen. Animals in Group I were normal and fed a standard diet; animals in Group II were given HFCD to prevent disease; animals in Group III were given HFCD plus exercise; while animals in Groups IV and V were given PHF at doses of 400 and 200 mg/kg p. o. Daily, respectively, in addition to HFCD; while animals in Groups VI and VII were exercised obese rats prevented from gaining more weight had their serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels lowered. HDL cholesterol was raised. Further, the liver biopsy showed increased mononuclear cells; fat globules numbered less; and the enzymes and cells that are regenerating were at lower levels. The polyherbal formulation plus exercise exhibited significant anti-obesity efficacy at 400 mg/kg p. o.; the effect was equivalent to orlistat plus exercise. The research employed HFCD-induced obese rats as a model to investigate the joint effects of PHF and exercise against obesity.

LncRNA-based control affects cardiac pathophysiologies like myocardial infarction, coronary artery disease, hypertrophy, and myotonic muscular dystrophy. This study used a gene-break transposon (GBT) to screen zebrafish (Danio rerio) for insertional mutagenesis. We identified three insertional mutants where the GBT captured a cardiac gene. One of the adult viable GBT mutants had bradycardia (heart arrhythmia) and enlarged cardiac chambers or hypertrophy; we named it “bigheart.” Bigheart mutant insertion maps to grin2bb or N-methyl D-aspartate receptor (NMDAR2B) gene intron 2 in reverse orientation. Rapid amplification of adjacent cDNA ends analysis suggested a new insertion site transcript in the intron 2 of grin2bb. Analysis of the RNA sequencing of wild-type zebrafish heart chambers revealed a possible new transcript at the insertion site. As this putative lncRNA transcript satisfies the canonical signatures, we called this transcript grin2bb associated RNA transcript (grin2bbART). Using in situ hybridization, we confirmed localized grin2bbART expression in the heart, central nervous system, and muscles in the developing embryos and wild-type adult zebrafish atrium and bulbus arteriosus. The bigheart mutant had reduced Grin2bbART expression. We showed that bigheart gene trap insertion excision reversed cardiac-specific arrhythmia and atrial hypertrophy and restored grin2bbART expression. Morpholino-mediated antisense downregulation of grin2bbART in wild-type zebrafish embryos mimicked bigheart mutants; this suggests grin2bbART is linked to bigheart. Cardiovascular tissues use Grin2bb as a calcium-permeable ion channel. Calcium imaging experiments performed on bigheart mutants indicated calcium mishandling in the heart. The bigheart cardiac transcriptome showed differential expression of calcium homeostasis, cardiac remodeling, and contraction genes. Western blot analysis highlighted Camk2d1 and Hdac1 overexpression. We propose that altered calcium activity due to disruption of grin2bbART, a putative lncRNA in bigheart, altered the Camk2d-Hdac pathway, causing heart arrhythmia and hypertrophy in zebrafish.

Abstract Background Xenopus has served as a valuable model system for biomedical research over the past decades. Notably, ADAR was first detected in frog oocytes and embryos as an activity that unwinds RNA duplexes. However, the scope of A-to-I RNA editing by the ADAR enzymes in Xenopus remains underexplored. Results Here, we identify millions of editing events in Xenopus with high accuracy and systematically map the editome across developmental stages, adult organs, and species. We report diverse spatiotemporal patterns of editing with deamination activity highest in early embryogenesis before zygotic genome activation and in the ovary. Strikingly, editing events are poorly conserved across different Xenopus species. Even sites that are detected in both X. laevis and X. tropicalis show largely divergent editing levels or developmental profiles. In protein-coding regions, only a small subset of sites that are found mostly in the brain are well conserved between frogs and mammals. Conclusions Collectively, our work provides fresh insights into ADAR activity in vertebrates and suggest that species-specific editing may play a role in each animal’s unique physiology or environmental adaptation.

Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections.

Stomata regulates conductance, transpiration and photosynthetic traits in plants. Increased stomatal density may contribute to enhanced water loss and thereby help improve the transpirational cooling process and mitigate the high temperature-induced yield losses. However, genetic manipulation of stomatal traits through conventional breeding still remains a challenge due to problems involved in phenotyping and the lack of suitable genetic materials. Recent advances in functional genomics in rice identified major effect genes determining stomatal traits, including its number and size. Widespread applications of CRISPR/Cas9 in creating targeted mutations paved the way for fine tuning the stomatal traits for enhancing climate resilience in crops. In the current study, attempts were made to create novel alleles of OsEPF1 (Epidermal Patterning Factor), a negative regulator of stomatal frequency/density in a popular rice variety, ASD 16, using the CRISPR/Cas9 approach. Evaluation of 17 T0 progenies identified varying mutations (seven multiallelic, seven biallelic and three monoallelic mutations). T0 mutant lines showed a 3.7–44.3% increase in the stomatal density, and all the mutations were successfully inherited into the T1 generation. Evaluation of T1 progenies through sequencing identified three homozygous mutants for one bp insertion. Overall, T1 plants showed 54–95% increased stomatal density. The homozygous T1 lines (# E1-1-4, # E1-1-9 and # E1-1-11) showed significant increase in the stomatal conductance (60–65%), photosynthetic rate (14–31%) and the transpiration rate (58–62%) compared to the nontransgenic ASD 16. Results demonstrated that the genetic alterations in OsEPF1 altered the stomatal density, stomatal conductance and photosynthetic efficiency in rice. Further experiments are needed to associate this technology with canopy cooling and high temperature tolerance.

Male and female mice deficient in DIAPH1 are protected from the development of experimental atherosclerosis and display reduced cholesterol levels; these changes are linked to the regulation of SREBP1 subcellular localization.

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The designed molecules were then further subjected to ADMET and molecular docking studies. Out of 34 designed compounds, the top-10 molecules from the computation studies were synthesized, characterized, and evaluated for COX-2 inhibition and anti-cancer activity. Initially, the target compounds were screened for the protein denaturation assay. The results of the top-five molecules T2, T3, T5, T6, and T9 were further subjected to in vitro COX-2 enzymatic assay and anti-cancer activity. As far as COX-2 inhibitory activity is considered, two compounds, T3 and T5, exhibited the half maximum inhibitory concentration (IC50) at 0.781 µM and 0.781 µM respectively. Further, the two compounds T3 and T5, when evaluated for COX-1 inhibition, exhibited excellent inhibitory activity with T3 IC50 of 4.655μM and T5 with IC50 of 5.596 μM. The compound T5 showed more significant human COX-2 inhibition, with a selectivity index of 7.16, when compared with T3, which had a selectivity index of 5.96. Further, in vitro anti-cancer activity was screened against two cancer cell lines in which compounds T2 and T3 were active against A549 cell lines and T6 was active against the HepG2 cell line. Stronger binding energy was found by comparing MM-PBSA simulations with molecular docking, which suggests that compounds T3 and T5 have a better possibility of being effective compounds, in which T5 showed higher binding affinity. The results suggest that these compounds have the potential to develop effective COX-2 inhibitors as anti-cancer agents.

Objective: Psychostimulant use induces oxidative stress and alters redox imbalance, influencing epigenetic signatures in the central nervous system (CNS). Among the various epigenetic changes, DNA methylation is directly linked to oxidative stress metabolism via critical redox intermediates such as NAD+, S-adenosylmethionine (SAM), and 2-oxoglutarate. Fluctuations in these intermediates directly influence epigenetic signatures, which leads to detectable alterations in gene expression and protein modification. This review focuses on recent advances in the impact of psychostimulant use on redox-imbalance-induced DNA methylation to develop novel epigenetics-based early interventions. Methods: This review is based on collective research data obtained from the PubMed, Science Direct, and Medline databases. The keywords used in the electronic search in these databases were redox, substance use disorder, psychostimulants, DNA methylation, and neurological diseases. Results: Instability in DNA methylation levels and redox expression effects are reported in various behavioral models stimulated by psychostimulants and opioids, indicating the widespread involvement of epigenetic changes in DNA methylation signatures in neurological disorders. Discussion: This review summarizes the need for more studies and experimental evaluations of DNA-methylation-based strategies that may help to understand the association between psychostimulant use and oxidative stress or redox-linked metabolic recalibration influencing neuronal impairments.

Mental fatigue has shown to be one of the root causes of decreased productivity and overall cognitive performance, by decreasing an individual’s ability to inhibit responses, process information and concentrate. The effects of mental fatigue have led to occupational errors and motorway accidents. Early detection of mental fatigue can prevent the escalation of symptoms that may lead to chronic fatigue syndrome and other disorders. To date, in clinical settings, the assessment of mental fatigue and stress is done through self-reported questionnaires. The validity of these questionnaires is questionable, as they are highly subjective measurement tools and are not immune to response biases. This review examines the wider presence of mental fatigue in the general population and critically compares its various detection techniques (i.e., self-reporting questionnaires, heart rate variability, salivary cortisol levels, electroencephalogram, and saccadic eye movements). The ability of these detection tools to assess inhibition responses (which are sensitive enough to be manifested in a fatigue state) is specifically evaluated for a reliable marker in identifying mentally fatigued individuals. In laboratory settings, antisaccade tasks have been long used to assess inhibitory control and this technique can potentially serve as the most promising assessment tool to objectively detect mental fatigue. However, more studies need to be conducted in the future to validate and correlate this assessment with other existing measures of mental fatigue detection. This review is intended for, but not limited to, mental health professionals, digital health scientists, vision researchers, and behavioral scientists.

Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to the diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain-like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD. Despite the HFHFrHC diet upregulating MLKL (2.5-fold), WT mice livers showed no increase in necroptosis markers or associated proinflammatory cytokines. Surprisingly, Mlkl−/− mice experienced exacerbated liver inflammation without protection from diet-induced liver damage, steatosis, or fibrosis. In contrast, Mlkl+/− mice showed a significant reduction in these parameters that was associated with elevated Pparα and Pparγ levels. Both Mlkl−/− and Mlkl+/− mice on the HFHFrHC diet resisted diet-induced obesity, attributed to the increased beiging, enhanced oxygen consumption, and energy expenditure due to adipose tissue, and exhibited improved insulin sensitivity. These findings highlight the tissue-specific effects of MLKL on the liver and adipose tissue, and they suggest a dose-dependent effect of MLKL on liver pathology.

Marine microorganisms have been demonstrated to be an important source for bioactive molecules. In this paper we report the synthesis of Ni nanoparticles (NiSNPs) used as reducing and capping agents for five bacterial strains isolated from an Antarctic marine consortium: Marinomonas sp. ef1, Rhodococcus sp. ef1, Pseudomonas sp. ef1, Brevundimonas sp. ef1, and Bacillus sp. ef1. The NiSNPs were characterized by Ultraviolet–visible (UV–vis) spectroscopy, Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopic analysis. The maximum absorbances in the UV–Vis spectra were in the range of 374 nm to 422 nm, corresponding to the Surface plasmon resonance (SPR) of Nickel. DLS revealed NiSNPs with sizes between 40 and 45 nm. All NiSNPs were polycrystalline with a face-centered cubic lattice, as revealed by XRD analyses. The NiSNPs zeta potential values were highly negative. TEM analysis showed that the NiSNPs were either spherical or rod shaped, well segregated, and with a size between 20 and 50 nm. The FTIR spectra revealed peaks of amino acid and protein binding to the NiSNPs. Finally, all the NiSNPs possess significant antimicrobial activity, which may play an important role in the management of infectious diseases affecting human health.

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

Sporisorium reilianum, the causal agent of sorghum (Sorghum bicolor (L.) Moench) head smut, is present in most sorghum-producing regions. This seed replacement fungal disease can reduce yield by up to 80% in severely infected fields. Management of this disease can be challenging due to the appearance of different pathotypes within the pathogenic population. In this research, the genetic variability and pathogenicity of isolates collected from five Texas Counties was conducted. Due to the lack of available space, 21 out of 32 sequenced isolates were selected and evaluated for virulence patterns on the six sorghum differentials, Tx7078, BTx635, SC170-6-17 (TAM2571), SA281 (Early Hegari), Tx414, and BTx643. The results reveal the occurrence of a new pathotype, 1A, and four previously documented US pathotypes when the 21 isolates were evaluated for virulence patterns on the differentials. The most prevalent was pathotype 5, which was recovered from Brazos, Hidalgo, Nueces, and Willacy Counties, Texas. This pathotype was followed by 1A and 6 in frequency of recovery. Pathotype 4 was identified only from isolates collected from Hidalgo County, while pathotype 1 was from Burleson County, Texas. It appeared that the previous US head smut pathotypes (2 and 3) are no longer common, and the new pathotypes, 1A, 5, and 6, are now predominant. The phylogenetic tree constructed from the single-nucleotide polymorphism (SNP) data through the neighbor-joining method showed high genetic diversity among the tested isolates. Some of the diverse clades among the tested isolates were independent of their sampled locations. Notably, HS37, HS49, and HS65 formed a clade and were classified as 1A in the virulence study, while HS 61 and HS 66, which were collected from Nueces County, were grouped and identified as pathotype 5.

Anthracnose, incited by Colletotrichum sublineola, is the most destructive foliar disease of sorghum and, under severe conditions, yield losses can exceed 80% on susceptible cultivars. The hyper-variable nature of the pathogen makes its management challenging despite the occurrence of several resistant sources. In this study, the genetic variability and pathogenicity of 140 isolates of C. sublineola, which were sequenced using restriction site-associated sequencing (RAD-Seq), resulted in 1244 quality SNPs. The genetic relationship based on the SNP data showed low to high genetic diversity based on isolates’ origin. Isolates from Georgia and North Carolina were grouped into multiple clusters with some level of genetic relationships to each other. Even though some isolates from Texas formed a cluster, others clustered with isolates from Puerto Rico. The isolates from Puerto Rico showed scattered distribution, indicating the diverse nature of these isolates. A population structure and cluster analysis revealed that the genetic variation was stratified into eight populations and one admixture group. The virulence pattern of 30 sequenced isolates on 18 sorghum differential lines revealed 27 new pathotypes. SC748-5, SC112-14, and Brandes were resistant to all the tested isolates, while BTx623 was susceptible to all. Line TAM428 was susceptible to all the pathotypes, except for pathotype 26. Future use of the 18 differentials employed in this study, which contains cultivars/lines which have been used in the Americas, Asia, and Africa, could allow for better characterization of C. sublineola pathotypes at a global level, thus accelerating the development of sorghum lines with stable resistance to the anthracnose pathogen.

This study aims to increase Bacillus and Streptomyces antagonistic activity against the root rot and wilt diseases of pulses caused by Macrophomina phaseolina and Fusarium oxysporum f. sp. udum, respectively. To increase antagonistic action, Bacillus subtilis BRBac4, Bacillus siamensis BRBac21, and Streptomyces cavourensis BRAcB10 were subjected to random mutagenesis using varying doses of gamma irradiation (0.5–3.0 kGy). Following the irradiation, 250 bacterial colonies were chosen at random for each antagonistic strain and their effects against pathogens were evaluated in a plate assay. The ERIC, BOX, and random amplified polymorphic studies demonstrated a clear distinction between mutant and wild-type strains. When mutants were compared to wild-type strains, they showed improved plant growth-promoting characteristics and hydrolytic enzyme activity. The disease suppression potential of the selected mutants, B. subtilis BRBac4-M6, B. siamensisi BRBac21-M10, and S. cavourensis BRAcB10-M2, was tested in green gram, black gram, and red gram. The combined inoculation of B. siamensis BRBac21-M10 and S. cavourensis BRAcB10-M2 reduced the incidence of root rot and wilt disease. The same treatment also increased the activity of the defensive enzymes peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase. These findings suggested that gamma-induced mutation can be exploited effectively to improve the biocontrol characteristics of Bacillus and Streptomyces. Following the field testing, a combined bio-formulation of these two bacteria may be utilised to address wilt and root-rot pathogens in pulses.

Aquatic animals are continually being exposed to stressors under farming conditions, increasing risks to gut health that result in dysbiosis. Since restrictions are imposed on the frequent use of antibiotics in aquaculture, there is emerging demand for economically viable, environmentally safe, and sustainable alternatives for the intensive production of aquaculture species. The application of beneficial microorganisms as probiotics has been suggested and widely practiced in recent times. Bacteria and fungi are ubiquitous microorganisms that can grow in various environments where organic substrates are available. Being rich in nutrients, a fish’s aquatic environment and gastrointestinal tract confer a favorable culture milieu for the microorganisms. However, the colonization and probiotic potential of fungi and mycelial bacteria resembling fungi (actinobacteria), either in the culture environment or within the gastrointestinal tracts of fish, have received less emphasis. Apart from bacilli and lactic acid bacteria, as the most conventionally used probiotics in aquaculture, numerous studies have focused on other promising alternatives. Diverse species of yeasts and molds belonging to the kingdom ‘Fungi’ have been characterized for their prospective roles in nutrition, immunomodulation, and disease prevention in fish. Bioactive compounds such as manno-oligosaccharides and β-glucans are recognized as fungal postbiotics that improve innate immunity and disease resistance in fish. Actinobacteria are known to possess different hydrolytic enzymes and novel secondary metabolites representing their probiotic attributes. The application of these groups in water quality amelioration has also been explored. Thus, this paper presents an overview of the present status of knowledge pertaining to the effects of yeasts (Candida, Cryptococcus, Debaryomyces, Geotrichum, Leucosporidium, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Sporidiobolus, Sporobolomyces, Trichosporon and Yarrowialipolytica), molds (Aspergillus spp.) and actinobacteria (Streptomyces) as probiotics in finfish aquaculture, as well as their occurrence within the gastrointestinal tracts of finfish. Furthermore, probiotic mechanisms, selection criteria, and future perspectives on using fungi and actinobacteria as promising probiotics are discussed.

The salinization and sodification of agricultural lands in arid and semi-arid regions of the world are two limiting factors in crop production. In India, an area of about 6.72 million ha is salt-affected, of which 3.77 million ha is sodic soil. To evaluate the reclamation potential of soil amendment, a laboratory incubation study was conducted at the Agricultural College and Research Institute, Tiruchirappalli (2022). Different soil amendments, viz., T1-Pongamia GLM @ 6.25 t ha−1, T2-Pressmud @ 10 t ha−1, T3-CSR GROMOR 25 kg ha−1, T4-Marine gypsum 50% GR, T5-Marine gypsum @ 50% GR + Pongamia GLM 6.25 t ha−1, T6-Marine gypsum 50% GR + Pressmud 10 t ha−1, T7-Marine gypsum 50% GR + CSR GROMOR 25 kg ha−1 and T8-Control (no amendments), were used for incubation. After 90 days of incubation, a pot culture using post-incubated soil was raised to study the seedling parameters of green gram, which was laid out in a randomized block design with three replications. The analysis of post-incubated soil using ICP-MS shows higher levels of cations, viz., Ca (+67%), Mg (+65%) and K (+66%), were found in marine gypsum @ 50% GR + CSR GROMOR @ 25 kg ha−1 with lower values of pH (−15%), EC (−63%), ESP (−39%) and Na (−58%) compared to the control. The same treatment recorded higher chlorophyll, relative water content and seedling vigor index I and II in green gram. The results indicated that marine gypsum + CSR GROMOR had a positive impact on reducing soil sodicity and improving soil fertility.

The purpose of this article is to investigate a suitable path planning algorithm for a multi-agent-based Plug & Produce system that can run online during manufacturing. This is needed since in such systems, resources can move around frequently, making it hard to manually create robot paths. To find a suitable algorithm and verify that it can be used online in a Plug & Produce system, a comparative study between various existing sampling-based path planning algorithms was conducted. Much research exists on path planning carried out offline; however, not so much is performed in online path planning. The specific requirements for Plug & Produce are to generate a path fast enough to eliminate manufacturing delays, to make the path energy efficient, and that it run fast enough to complete the task. The paths are generated in a simulation environment and the generated paths are tested for robot configuration errors and errors due to the target being out of reach. The error-free generated paths are then tested on an industrial test bed environment, and the energy consumed by each path was measured and validated with an energy meter. The results show that all the implemented optimal sampling-based algorithms can be used for some scenarios, but that adaptive RRT and adaptive RRT* are more suitable for online applications in multi-agent systems (MAS) due to a faster generation of paths, even though the environment has more constraints. For each generated path the computational time of the algorithm, move-along time and energy consumed are measured, evaluated, compared, and presented in the article.

(1) Background: The latest research illustrates that microglia phenotype is not the binary ‘resting’ and ‘activated’ profiles. Instead, there is wide diversity in microglia states. Similarly, when testing different stimulation protocols for BV2 microglia, we discovered differences in the response of the cells in terms of the production of intracellular ROS (iROS), nitric oxide (NO), CD40 expression, and migratory capacity. (2) Methods: BV2 microglia were treated with single interferon gamma (IFN-γ) stimulation, LPS/IFN-γ co-stimulation, and priming with IFN-γ followed by stimulation with LPS for 24 h. The responses of BV2 microglia were then assessed using the H2DCFDA test for iROS, the Griess assay for NO, immunophenotyping for CD40/CD11b/MHC II, and migration using a transwell apparatus. (3) Results: Single stimulation with IFN-γ induced NO but not ROS in BV2 microglia. Co-stimulation with LPS200IFN-γ2.5 induced a higher iROS production (a 9.2-fold increase) and CD40 expression (28031 ± 8810.2 MFI), compared to priming with primedIFN-γ50LPS100 (a 4.0-fold increase in ROS and 16764 ± 1210.8 MFI of CD40). Co-stimulation also induced cell migration. On the other hand, priming BV2 microglia (primedIFN-γ50LPS100) resulted in a higher NO production (64 ± 1.4 µM) compared to LPS200IFN-γ2.5 co-stimulation (44 ± 1.7 µM). Unexpectedly, priming inhibited BV2 migration. (4) Conclusions: Taken together, the findings from this project reveal the ability of co-stimulation and priming in stimulating microglia into an inflammatory phenotype, and the heterogeneity of microglia responses towards different stimulating approaches.

Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be necessary to avoid inappropriate treatment strategies. Hence, the search for other alternative strategies as effective biofilm treatment options has become a growing area of research. The current review aims to give an overview of the mechanisms governing biofilm formation and the different strategies employed so far in the control of biofilm infections caused by P. aeruginosa. Moreover, this review can also help researchers to search for new antibiofilm agents to tackle the effect of biofilm infections that are currently imprudent to conventional antibiotics.

The shoulder is a unique and complex joint in the human body with three bones and four joints, which makes it the most unstable joint in the body due to the amount of motion. To improve approaches toward understanding the performance of overhead throwing movements, this systematic review summarizes the type of analysis related to shoulder biomechanics involving overhead sporting motions. A search of seven databases identified 33 eligible studies, which were subsequently scored using the Modified Coleman Methodology Score scale. A total of nine articles from badminton, seven from baseball, five from volleyball, five from tennis, three from cricket, and one from softball were reviewed. All 33 studies evaluated shoulder kinematics and 12 of them also investigated the forces and torques (kinetics). The most common methods used were 3D motion analysis (76%), digital video cameras (15%), electromagnetic tracking system (6%), and finally 3% used IMU sensors. Overall, shoulder external rotation during the back swing, internal rotation, and elbow extension during the forward acceleration phase were the strongest predictors of high velocity overhead throwing movement. The findings provide some useful insights and guidance to researchers in their future contribution to the existing body of literature on shoulder overhead throwing movement biomechanics.

Electric vehicles (EVs) are universally recognized as an incredibly effective method of lowering gas emissions and dependence on oil for transportation. Electricity, rather than more traditional fuels like gasoline or diesel, is used as the main source of energy to recharge the batteries in EVs. Future oil demand should decline as a result of the predicted rise in the number of EVs on the road. The charging infrastructure is considered as a key element of EV technology where the recent research is mostly focused. A strong charging infrastructure that serves both urban and rural areas, especially those with an unstable or nonexistent electrical supply, is essential in promoting the global adoption of EVs. Followed by different EV structures such as fuel-cell- and battery-integrated EVs, the charging infrastructures are thoroughly reviewed in three modes, specifically—off-grid (standalone), grid-connected, and hybrid modes (capable of both standalone and grid-connected operations). It will be interesting for the readers to understand in detail several energy-source-based charging systems and the usage of charging stations for different power levels. Towards the improvement of the lifetime and efficiency of EVs, charging methods and charging stations in integration with microgrid architectures are thoroughly investigated. EVs are a multi-energy system, which requires effective power management and control to optimize energy utilization. This review article also includes an evaluation of several power management and control strategies followed by the impact assessment of EVs on the utility grid. The findings and the future research directions provided in this review article will be extremely beneficial for EV operators and research engineers.

Neuroendocrine-immune homeostasis in health and disease is a tightly regulated bidirectional network that influences predisposition, onset and progression of age-associated disorders. The complexity of interactions among the nervous, endocrine and immune systems necessitates a complete review of all the likely mechanisms by which each individual system can alter neuroendocrine-immune homeostasis and influence the outcome in age and disease. Dysfunctions in this network with age or external/internal stimuli are implicated in the development of several disorders including autoimmunity and cancer. The existence of sympathetic noradrenergic innervations on lymphoid organs in synaptic association with immune cells that express receptors for endocrine mediators such as hormones, neural mediators such as neurotransmitters and immune effector molecules such as cytokines explains the complicated nature of the regulatory pathways that must always maintain homeostatic equilibrium within and among the nervous, endocrine and immune systems. The incidence, development and progression of cancer, affects each of the three systems by disrupting regulatory pathways and tipping the scales away from homeostasis to favour pathways that enable it to evade, override and thrive by using the network to its advantage. In this review, we have explained how the neuroendocrine-immune network is altered in female reproductive aging and cancer, and how these modulations contribute to incidence and progression of cancer and hence prove to be valuable targets from a therapeutic standpoint. Reproductive aging, stress-associated central pathways, sympathetic immunomodulation in the periphery, inflammatory and immunomodulatory changes in central, peripheral and tumor-microenvironment, and neuro-neoplastic associations are all likely candidates that influence the onset, incidence and progression of cancer.

Traditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which cannot be correctly represented by the traditional fixed set of static coordinates. Representing such protein behaviors remains challenging and necessarily involves a complex interpretation of conformational states, including probabilistic descriptions. Relating protein dynamics and multiple conformations to their function as well as their physiological context (e.g., post-translational modifications and subcellular localization), therefore, remains elusive for much of the proteome, with studies to investigate the effect of protein dynamics relying heavily on computational models. We here investigate the possibility of delineating three classes of protein conformational behavior: order, disorder, and ambiguity. These definitions are explored based on three different datasets, using interpretable machine learning from a set of features, from AlphaFold2 to sequence-based predictions, to understand the overlap and differences between these datasets. This forms the basis for a discussion on the current limitations in describing the behavior of dynamic and ambiguous proteins.

Robust activation of mTOR (mammalian target of rapamycin) signaling in diabetes exacerbates myocardial injury following lethal ischemia due to accelerated cardiomyocyte death with cardiac remodeling and inflammatory responses. We examined the effect of rapamycin (RAPA, mTOR inhibitor) on cardiac remodeling and inflammation following myocardial ischemia/reperfusion (I/R) injury in diabetic rabbits. Diabetic rabbits (DM) were subjected to 45 min of ischemia and 10 days of reperfusion by inflating/deflating a previously implanted hydraulic balloon occluder. RAPA (0.25 mg/kg, i.v.) or DMSO (vehicle) was infused 5 min before the onset of reperfusion. Post-I/R left ventricular (LV) function was assessed by echocardiography and fibrosis was evaluated by picrosirius red staining. Treatment with RAPA preserved LV ejection fraction and reduced fibrosis. Immunoblot and real-time PCR revealed that RAPA treatment inhibited several fibrosis markers (TGF-β, Galectin-3, MYH, p-SMAD). Furthermore, immunofluorescence staining revealed the attenuation of post-I/R NLRP3-inflammasome formation with RAPA treatment as shown by reduced aggregation of apoptosis speck-like protein with a caspase recruitment domain and active-form of caspase-1 in cardiomyocytes. In conclusion, our study suggests that acute reperfusion therapy with RAPA may be a viable strategy to preserve cardiac function with the alleviation of adverse post-infarct myocardial remodeling and inflammation in diabetic patients.

The main aim of this study is to synthesize contrast microbubbles (MB) functionalized with engineered protein ligands using a microfluidic device to target breast cancer specific vascular B7-H3 receptor in vivo for diagnostic ultrasound imaging. We used a high-affinity affibody (ABY) selected against human/mouse B7-H3 receptor for engineering targeted MBs (TMBs). We introduced a C-terminal cysteine residue to this ABY ligand for facilitating site-specific conjugation to DSPE-PEG-2K-maleimide (M. Wt = 2.9416 kDa) phospholipid for MB formulation. We optimized the reaction conditions of bioconjugations and applied it for microfluidic based synthesis of TMBs using DSPE-PEG-ABY and DPPC liposomes (5:95 mole %). The binding affinity of TMBs to B7-H3 (MBB7-H3) was tested in vitro in MS1 endothelial cells expressing human B7-H3 (MS1B7-H3) by flow chamber assay, and by ex vivo in the mammary tumors of a transgenic mouse model (FVB/N-Tg (MMTV-PyMT)634Mul/J), expressing murine B7-H3 in the vascular endothelial cells by immunostaining analyses. We successfully optimized the conditions needed for generating TMBs using a microfluidic system. The synthesized MBs showed higher affinity to MS1 cells engineered to express higher level of hB7-H3, and in the endothelial cells of mouse tumor tissue upon injecting TMBs in a live animal. The average number (mean ± SD) of MBB7-H3 binding to MS1B7-H3 cells was estimated to be 354.4 ± 52.3 per field of view (FOV) compared to wild-type control cells (MS1WT; 36.2 ± 7.5/FOV). The non-targeted MBs did not show any selective binding affinity to both the cells (37.7 ± 7.8/FOV for MS1B7-H3 and 28.3 ± 6.7/FOV for MS1WT cells). The fluorescently labeled MBB7-H3 upon systemic injection in vivo co-localized to tumor vessels, expressing B7-H3 receptor, as validated by ex vivo immunofluorescence analyses. We have successfully synthesized a novel MBB7-H3 via microfluidic device, which allows us to produce on demand TMBs for clinical applications. This clinically translatable MBB7-H3 showed significant binding affinity to vascular endothelial cells expressing B7-H3 both in vitro and in vivo, which shows its potential for clinical translation as a molecular ultrasound contrast agent for human applications.

Exploration of seaweeds to unravel their bioactive metabolites from the perspective of wider applications gained substantial importance. The present study was performed to investigate the total phenolic, flavonoid, tannin content, antioxidant activity and antibacterial potential of various solvent extracts of green seaweed Caulerpa racemosa. The methanolic extract showed higher phenolic (11.99 ± 0.48 mg gallic acid equivalents/g), tannin (18.59 ± 0.54 mg tannic acid equivalents/g) and flavonoid (33.17 ± 0.76 mg quercetin equivalents/g) content than other extracts. Antioxidant activity was determined by using 2,2-diphenylpicrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay with different concentrations of C. racemosa extracts. The methanolic extract showed higher scavenging potential in both the DPPH and ABTS activity with the inhibition value of 54.21 ± 1.39% and 76.62 ± 1.08%, respectively. Bioactive profiling was also identified by using Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FT-IR) techniques. These studies revealed the presence of valuable bioactive compounds in C. racemosa extracts and these compounds might be responsible for antimicrobial, antioxidant, anticancer and anti-mutagenic properties. Major compounds identified in GC-MS were 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, 3-hexadecene and Phthalic acid. In terms of antibacterial activity, C. racemosa has promising antibacterial potential against aquatic pathogens Aeromonas hydrophila, Aeromonas veronii and Aeromonas salmonicida. Further evaluation studies focusing aquatic related aspects would reveal the novel bioproperties and applications of C. racemosa.

Overactivation of immune responses is a hallmark of autoimmune disease pathogenesis. This includes the heightened production of inflammatory cytokines such as Tumor Necrosis Factor α (TNFα), and the secretion of autoantibodies such as isotypes of rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA). Fcγ receptors (FcγR) expressed on the surface of myeloid cells bind Immunoglobulin G (IgG) immune complexes. Recognition of autoantigen-antibody complexes by FcγR induces an inflammatory phenotype that results in tissue damage and further escalation of the inflammatory response. Bromodomain and extra-terminal protein (BET) inhibition is associated with reduced immune responses, making the BET family a potential therapeutic target for autoimmune diseases such as rheumatoid arthritis (RA). In this paper, we examined the BET inhibitor PLX51107 and its effect on regulating FcγR expression and function in RA. PLX51107 significantly downregulated expression of FcγRIIa, FcγRIIb, FcγRIIIa, and the common γ-chain, FcϵR1-γ, in both healthy donor and RA patient monocytes. Consistent with this, PLX51107 treatment attenuated signaling events downstream of FcγR activation. This was accompanied by a significant decrease in phagocytosis and TNFα production. Finally, in a collagen-induced arthritis model, PLX51107-treatment reduced FcγR expression in vivo accompanied by a significant reduction in footpad swelling. These results suggest that BET inhibition is a novel therapeutic approach that requires further exploration as a treatment for patients with RA.

Tilapia is a widely cultured species native to Africa; these fish are prolific breeders and constitute an economically important fish species supplying higher-quality protein. To meet the global food demand and achieve the UN’s Sustainable Developmental Goals (SDG), the aquaculture industry has conceived of productive solutions with the potential for adaptability, palatability, and profitability. Tilapia may play a vital role with respect to the possibility for sustainability in the nutrition and aquaculture sectors. India contributes to the promotion of aquacultural practices through a structural framework focused on agricultural, environmental, geographical, and socio-economic factors that provide opportunities for tilapia farming. Globally, the Indian aquaculture sector is currently the second largest in terms of aquacultural production but is moving toward different species that meet SDG and facilitate international marketing opportunities. The farming of aquacultural species with innovative technology constitutes an efficient use of resources. Productive research on feeding, disease management, construction, and layout helps overcome the challenges faced in aquaculture. These focused and sustained factors of the aquaculture industry offer a latent contribution to global food security. This review reports on the state of the art, the challenges regarding tilapia aquaculture in India, and the Indian government’s schemes, missions, subsidies, projects and funding related to tilapia production.

Gingipains (RgpA, RgpB, and Kgp) are major virulence factors of the periodontitis-causing bacterium Porphyromonas gingivalis. Isolation of gingipains from the crude protein sample of P. gingivalis is critical for studying the underlying invasion mechanism that contributes to periodontitis, Alzheimer’s disease, and cardiovascular disease (CVD). Chromatographic processes and molecular cloning are two standard techniques often used for gingipains isolation, which are time-consuming and costly. In this study, considerably easier methods based on passive-mediated diffusion gel elution and gelatin zymogram were used to isolate and characterize gingipains. Importantly, proteins eluted from Native-PAGE showed enzymatic activity for both Rgp and Kgp. In gelatin zymography, the proteins with a molecular size of ~50 kDa and above 245 kDa were suggested as arginine-specific gingipains. The passive diffusion-mediated gel elution method is a simpler technique to isolate gingipains from crude protein samples of P. gingivalis. By using covalent and highly specific gingipain inhibitors, gelatin zymography enabled an individual characterization of gingipain activity and inhibition. Finally, this protocol can be easily extended by adding the isoelectric focusing to further improve the protein separation and characterization.

Broadcasting, radar, sonar and space telecommunication systems use phased arrays to produce directed signals to be transmitted at the desired angle. This system requires a large number of antenna elements. The presence of faulty element(s) in an array causes asymmetry, which results in a deformed radiation pattern with higher sidelobe levels. Higher sidelobe levels indicate waste of energy by transmitting and receiving signals in unwanted directions. Hence, it is important to develop a method that detects faulty elements and corrects the radiation pattern. To correct the failed radiation pattern, failed elements in an array must be identified first. There have been various studies conducted on linear array failed radiation pattern correction and the finding of faulty elements, but investigation on the planar array is limited. Further, the optimization suggested for linear arrays does not necessarily work for the planar array. In this study, planar array faulty antenna detection was developed with pattern search (PS), simulated annealing (SA), and particle swarm optimization (PSO) methods by reducing the Signal to Noise Ratio (SNR) as the objective function. The analysis was varied for 8 × 8 and 6 × 6 planar arrays with different types of failures. The results were compared to find the best method to identify the faulty element’s location in a planar array. The pattern search method produced outstanding results in finding the faulty element’s locations by providing 100% accuracy for all types of failure, while other methods failed to do the same.

Parrish et al. demonstrate the modification of an incoming solar spectrum through downconversion of high energy UV/blue photons into orange/red photons using luminescent quantum dot films, leading to improved growth of leaf vegetables. Such technology can improve greenhouse productivity while reducing energy costs and can be useful to realize self-sustaining human settlements beyond Earth.

The present work was delineated to formulate and evaluate antioxidant and photoprotective properties of melanin produced by Pseudomonas mosseliistrain STSGRDS1 against the purchased fungal melanin STSGRDM1 as standard. Initially, antioxidant assay was examined for the isolated bacterial melanin STSGRDS1 against the standard melanin STSGRDM1 that already have substantiated to have the antioxidant ability by DPPH and ABTS, following with the detailed screening of radical scavenging activity were performed which includes the valuation of peroxides, hydroxyl radicals, reduction potential, and phosphomolybdenum method. This report depicts the antioxidant potential of the extracted melanin that could be further used as a potent antioxidant on scientific basis, as the percentage of free radical scavenging increased with increasing concentration of melanin. The study also signifies that bacterial melanin formulated creams had the potency to protect against ultraviolet (UV) rays with sun protection factor (SPF) enhancement ranging from 1.95 to 26.06 and transmission spectroscopy revealed that the formulations have satisfied protection against UV A and UV B rays with good average UV A protection factor indicating sunscreen activity of the pigment. As a result, the isolated bacterial strain has immense photoprotection potential and radical scavenging activity that can be resorted to in cosmetic formulations, UVprotection devices, etc.

The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN’s mg/Kg LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands (CO/H2S/N3-)$\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.

In recent years, green nanotechnology has gained considerable importance for the synthesis of nanoparticles due to its economic viability and biosafety. In the current study, silver nanoparticles were synthesized using two bacterial isolates, H2 and H3, which were isolated from soil samples collected from the Western Ghats, Tamil Nadu, and identified at the species level as Pantoeastewartii (H2) and Priestiaaryabhattai (H3) by sequencing their 16s rRNA genes. Intracellularly synthesized silver nanoparticles were characterized by UV–visible spectroscopy, Fourier transform infrared spectroscopy, atomic force microscopy, and particle size analysis. AFM studies show that both of the bacterial synthesized Ag NPs were circular-shaped and disaggregated, with an average size distribution of 4 nm for Pantoeastewartii and 3.6 nm for Priestiaaryabhattai. Furthermore, their larvicidal activity, antimicrobial, histopathological, and biotoxicity effects were determined. The synthesized Ag NPs exhibited potent larvicidal activity against fourth instars of Ae.aegypti, An.stephensi, and Cx.quinquefasciatus exposed to a 50 µg/mL concentration for 24 h based on their LC50 and LC90 values. Histopathological studies of the affected mosquito larvae clearly show damage to the epithelial cells, food bolus, basement membrane, muscles, and midgut parts. The maximum antimicrobial activity of Priestiaaryabhattai-synthesized Ag NPs was observed for Streptomyces varsoviensis MTCC-1537, and that of Pantoea stewartii-synthesized Ag NPs was against Escherichia coli MTCC-43. The toxicity test on non-target organisms such as Artemia nauplii and zebrafish embryos indicates no visible abnormalities or mortality after their exposure for 48h. It is concluded that silver nanoparticles can easily be synthesized using Pantoea stewartii (H2) and Priestia aryabhattai (H3) as capping and reducing agents. Silver nanoparticles showed potent larvicidal activities and could potentially be used in integrated vector control programs because they are safe for other inhabitants of the same aquatic environment as mosquito larvae.

Bioluminescence (BL) is an excellent optical readout for bioassays and molecular imaging. Herein, we accomplished new near infrared bioluminescence resonance energy transfer (NIR-BRET) templates for monitoring molecular events in cells with higher sensitivity. We first identified the best resonance energy donor for the NIR-BRET templates through the characterization of many coelenterazine (CTZ)–marine luciferase combinations. As a result, we found that NLuc–DBlueC and ALuc47–nCTZ combinations showed luminescence in the blue emission wavelength with excellent BL intensity and stability, for example, the NLuc–DBlueC and ALuc47–nCTZ combinations were 17-fold and 22-fold brighter than their second highest combinations, respectively, and were stably bright in living mammalian cells for at least 10 min. To harness the excellent BL properties to the NIR-BRET systems, NLuc and ALuc47 were genetically fused to fluorescent proteins (FPs), allowing large “blue-to-red” shifts, such as LSSmChe, LSSmKate2, and LSSmNep (where LSS means Large Stokes Shift). The excellent LSSmNep–NLuc combination showed approximately 170 nm large resonance energy shift from blue to red. The established templates were further utilized in the development of new NIR-BRET systems for imaging steroid hormone activities by sandwiching the ligand-binding domain of a nuclear receptor (NR-LBD) between the luciferase and the FP of the template. The NIR-BRET systems showed a specific luminescence signal upon exposure to steroid hormones, such as androgen, estrogen, and cortisol. The present NIR-BRET templates are important additions for utilizing their advantageous imaging of various molecular events with high efficiency and brightness in physiological samples.

The performance of speaker recognition systems is very well on the datasets without noise and mismatch. However, the performance gets degraded with the environmental noises, channel variation, physical and behavioral changes in speaker. The types of Speaker related feature play crucial role in improving the performance of speaker recognition systems. Gammatone Frequency Cepstral Coefficient (GFCC) features has been widely used to develop robust speaker recognition systems with the conventional machine learning, it achieved better performance compared to Mel Frequency Cepstral Coefficient (MFCC) features in the noisy condition. Recently, deep learning models showed better performance in the speaker recognition compared to conventional machine learning. Most of the previous deep learning-based speaker recognition models has used Mel Spectrogram and similar inputs rather than a handcrafted features like MFCC and GFCC features. However, the performance of the Mel Spectrogram features gets degraded in the high noise ratio and mismatch in the utterances. Similar to Mel Spectrogram, Cochleogram is another important feature for deep learning speaker recognition models. Like GFCC features, Cochleogram represents utterances in Equal Rectangular Band (ERB) scale which is important in noisy condition. However, none of the studies have conducted analysis for noise robustness of Cochleogram and Mel Spectrogram in speaker recognition. In addition, only limited studies have used Cochleogram to develop speech-based models in noisy and mismatch condition using deep learning. In this study, analysis of noise robustness of Cochleogram and Mel Spectrogram features in speaker recognition using deep learning model is conducted at the Signal to Noise Ratio (SNR) level from −5 dB to 20 dB. Experiments are conducted on the VoxCeleb1 and Noise added VoxCeleb1 dataset by using basic 2DCNN, ResNet-50, VGG-16, ECAPA-TDNN and TitaNet Models architectures. The Speaker identification and verification performance of both Cochleogram and Mel Spectrogram is evaluated. The results show that Cochleogram have better performance than Mel Spectrogram in both speaker identification and verification at the noisy and mismatch condition.

Delamination in laminated structures is a concern in high-performance structural applications, which challenges the latest non-destructive testing techniques. This study assesses the delamination damage in the glass fiber-reinforced laminated composite structures using structural health monitoring techniques. Glass fiber-reinforced rectangular laminate composite plates with and without delamination were considered to obtain the forced vibration response using an in-house developed finite element model. The damage was diagnosed in the laminated composite using machine learning algorithms through statistical information extracted from the forced vibration response. Using an attribute evaluator, the features that made the greatest contribution were identified from the extracted features. The selected features were further classified using machine learning algorithms, such as decision tree, random forest, naive Bayes, and Bayes net algorithms, to diagnose the damage in the laminated structure. The decision tree method was found to be a computationally effective model in diagnosing the delamination of the composite structure. The effectiveness of the finite element model was further validated with the experimental results, obtained from modal analysis using fabricated laminated and delaminated composite plates. Our proposed model showed 98.5% accuracy in diagnosing the damage in the fabricated composite structure. Hence, this research work motivates the development of online prognostic and health monitoring modules for detecting early damage to prevent catastrophic failures of structures.

This paper presents a new triple phase shift (TPS) closed-loop control scheme of a dual active bridge (DAB) LCC resonant DC/DC converter to improve wireless charging power transfer efficiency. The primary side inverter phase shift angle regulates the battery charging current/voltage. The secondary side rectifier phase shift angle regulates the rectifier AC load resistance to match its optimized setting. The inverter-to-rectifier phase shift angle is set to achieve unity power factor operation of the DAB rectifier and inverter. The mathematical formulation of the TPS shift control is given for each phase shift angle. The analytical calculation, circuit simulation, and experimental test are carried out in a power scaled-down DAB LCC resonant wireless charging converter laboratory hardware setup to validate the proposed TPS close-loop control scheme. The PLECS circuit simulation shows that DAB LCC resonant SiC MOSFET operates at zero-voltage-switching (ZVS) with a unity power factor in emulated constant current (CC) mode battery charging. In constant voltage (CV) mode operation, one inverter/rectifier Leg does not operate at ZVS switching when Sic MOSFET is switched on near zero current. The experimental results show that the efficiency is greatly improved for CV mode charging with large DC load resistance connected if rectifier AC load resistance matching control is enabled. The measured efficiency matches well with the analytical calculation. The estimated efficiency improvement will be much more significant for EV applications in the kW power range with greater winding loss. The challenges and possible solutions to implement TPS PWM modulation in two separate inverter and rectifier control hardware are explained for future TPS control algorithm development in practical wireless charging products.

The HfO2 nanoparticles and the nanocomposites of HfO2-graphene (10, 30, and 50 wt%) were prepared via precipitation and simple mixing method. The XRD pattern confirmed the presence of monoclinic HfO2 and hexagonal graphene in the nanocomposite. Raman spectroscopy studies revealed the formation of HfO2-graphene nanocomposite. According to SEM and TEM images the HfO2, NPs are spherical, and their size is less than 10 nm, anchored on the surface of the graphene sheets. The EDX spectrum shows carbon, oxygen, and HfO2 and reveals the formation of the HfO2-graphene nanocomposite. The UV-vis absorption spectra show the optical properties of synthesized HfO2-graphene nanocomposite. The study examines the influence of different ratios of the addition of graphene on the photocatalytic activity of HfO2-graphene. It was found that the HfO2-graphene (50 wt%) 40 mg nanocomposite exhibits enhanced photocatalytic activity than the bare HfO2 towards the methylene blue photodegradation, an aromatic pollutant in water under UV light irradiation, which can be applied optimally for individually wastewater management system. The HfO2-graphene (50 wt%) photocatalyst degrades 81 ± 2% of tetracycline in 180 min, implying that tetracycline can be degraded more efficiently under UV light. The enhancement in photocatalytic activity under UV light illumination can be attributed to the effective separation of photogenerated electrons, inhibiting recombination in the HfO2-graphene composite.

Cardiac hormones act on the regulation of blood pressure (BP) and cardiovascular homeostasis. These hormones include atrial and brain natriuretic peptides (ANP, BNP) and activate natriuretic peptide receptor-A (NPRA), which enhance natriuresis, diuresis, and vasorelaxation. In this study, we established the ANP-dependent homologous downregulation of NPRA using human embryonic kidney-293 (HEK-293) cells expressing recombinant receptor and MA-10 cells harboring native endogenous NPRA. The prolonged pretreatment of cells with ANP caused a time- and dose-dependent decrease in 125I-ANP binding, Guanylyl cyclase (GC) activity of receptor, and intracellular accumulation of cGMP leading to downregulation of NPRA. Treatment with ANP (100 nM) for 12 h led to an 80% decrease in 125I-ANP binding to its receptor, and BNP decreased it by 62%. Neither 100 nM c-ANF (truncated ANF) nor C-type natriuretic peptide (CNP) had any effect. ANP (100 nM) treatment also decreased GC activity by 68% and intracellular accumulation cGMP levels by 45%, while the NPRA antagonist A71915 (1 µM) almost completely blocked ANP-dependent downregulation of NPRA. Treatment with the protein kinase G (PKG) stimulator 8-(4-chlorophenylthio)-cGMP (CPT-cGMP) (1 µM) caused a significant increase in 125I-ANP binding, whereas the PKG inhibitor KT 5823 (1 µM) potentiated the effect of ANP on the downregulation of NPRA. The transfection of miR-128 significantly reduced NPRA protein levels by threefold compared to control cells. These results suggest that ligand-dependent mechanisms play important roles in the downregulation of NPRA in target cells.

The low response rates associated with immune checkpoint inhibitor (ICI) use has led to a surge in research investigating adjuvant combination strategies in an attempt to enhance efficacy. Repurposing existing drugs as adjuvants accelerates the pace of cancer immune therapy research; however, many combinations exacerbate the immunogenic response elicited by ICIs and can lead to adverse immune-related events. Metformin, a widely used type 2 diabetes drug is an ideal candidate to repurpose as it has a good safety profile and studies suggest that metformin can modulate the tumour microenvironment, promoting a favourable environment for T cell activation but has no direct action on T cell activation on its own. In the current study we used PET imaging with [18F]AlF-NOTA-KCNA3P, a radiopharmaceutical specifically targeting KV1.3 the potassium channel over-expressed on active effector memory T-cells, to determine whether combining PD1 with metformin leads to an enhanced immunological memory response in a preclinical colorectal cancer model. Flow cytometry was used to assess which immune cell populations infiltrate the tumours in response to the treatment combination. Imaging with [18F]AlF-NOTA-KCNA3P demonstrated that adjuvant metformin significantly improved anti-PD1 efficacy and led to a robust anti-tumour immunological memory response in a syngeneic colon cancer model through changes in tumour infiltrating effector memory T-cells.

Nosocomial infections pose an imminent challenge to hospitalized Coronavirus disease-19 (COVID-19) patients due to complex interplay of dysregulated immune response combined with immunomodulator therapy. In the pre-pandemic era, immunomodulatory therapy has shown benefit in certain autoimmune conditions with untamed inflammatory response. Efforts to recapitulate these immunomodulatory effects in COVID-19 patients has gained impetus and were followed by NIH COVID-19 expert panel recommendations. The current NIH guideline recommends interleukin-6 inhibitors (tocilizumab and sarilumab) and Janus kinase inhibitors (baricitinib and tofacitinib). Several landmark research trials like COVAVTA, EMPACTA, REMDACTA, STOP-COVID and COV BARRIER have detailed the various effects associated with administration of immunomodulators. The historical evidence of increased infection among patients receiving immunomodulators for autoimmune conditions, raised concerns regarding administration of immunomodulators in COVID-19 patients. The aim of this review article is to provide a comprehensive update on the currently available literature surrounding this issue. We reviewed 40 studies out of which 37 investigated IL-6 inhibitors and 3 investigated JAK inhibitors. Among the studies reviewed, the reported rates of nosocomial infections among the COVID-19 patients treated with immunomodulators were similar to patients receiving standard of care for COVID-19. However, these studies were not powered to assess the side effect profile of these medications. Immunomodulators, by dampening the pyrogenic response and inflammatory markers may delay detection of infections among the patients. This underscores the importance of long-term surveillance which are necessary to discover the potential risks associated with these agents.

Often, patients fail to respond to immune checkpoint inhibitor (ICI) treatment despite favourable biomarker status. Numerous chemotherapeutic agents have been shown to promote tumour immunogenicity when used in conjunction with ICIs; however, little is known about whether such combination therapies lead to a lasting immune response. Given the potential toxicity of ICI–chemotherapy combinations, identification of biomarkers that accurately predict how individuals respond to specific treatment combinations and whether these responses will be long lasting is of paramount importance. In this study, we explored [18F]AlF-NOTA-KCNA3P, a peptide radiopharmaceutical that targets the Kv1.3 potassium channel overexpressed on T-effector memory (TEM) cells as a PET imaging biomarker for lasting immunological memory response. The first-line colon cancer chemotherapies oxaliplatin and 5-fluorouracil were assessed in a syngeneic colon cancer model, either as monotherapies or in combination with PD1, comparing radiopharmaceutical uptake to memory-associated immune cells in the tumour. [18F]AlF-NOTA-KCNA3P reliably separated tumours with immunological memory responses from non-responding tumours and could be used to measure Kv1.3-expressing TEM cells responsible for durable immunological memory response to combination therapy in vivo.

The global targeted disruption of the natriuretic peptide receptor-A (NPRA) gene (Npr1) in mice provokes hypertension and cardiovascular dysfunction. The objective of this study was to determine the mechanisms regulating the development of cardiac fibrosis and dysfunction in Npr1 mutant mice. Npr1 knockout (Npr1−/−, 0-copy), heterozygous (Npr1+/−, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were treated with the transforming growth factor (TGF)-β1 receptor (TGF-β1R) antagonist GW788388 (2 µg/g body weight/day; ip) for 28 days. Hearts were isolated and used for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analyses. The Npr1−/− (0-copy) mice showed a 6-fold induction of cardiac fibrosis and dysfunction with markedly induced expressions of collagen-1α (3.8-fold), monocyte chemoattractant protein (3.7-fold), connective tissue growth factor (CTGF, 5.3-fold), α-smooth muscle actin (α-SMA, 6.1-fold), TGF-βRI (4.3-fold), TGF-βRII (4.7-fold), and phosphorylated small mothers against decapentaplegic (pSMAD) proteins, including pSMAD-2 (3.2-fold) and pSMAD-3 (3.7-fold), compared with wild-type mice. The expressions of phosphorylated extracellular-regulated kinase ERK1/2 (pERK1/2), matrix metalloproteinases-2, -9, (MMP-2, -9), and proliferating cell nuclear antigen (PCNA) were also significantly upregulated in Npr1 0-copy mice. The treatment of mutant mice with GW788388 significantly blocked the expression of fibrotic markers, SMAD proteins, MMPs, and PCNA compared with the vehicle-treated control mice. The treatment with GW788388 significantly prevented cardiac dysfunctions in a sex-dependent manner in Npr1 0-copy and 1-copy mutant mice. The results suggest that the development of cardiac fibrosis and dysfunction in mutant mice is predominantly regulated through the TGF-β1-mediated SMAD-dependent pathway.