Natural product inspired diastereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones and their in-silico studies.

Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

Recent advances in the synthesis and utility of thiazoline and its derivatives.

Thiazolines and their derivatives hold significant importance in the field of medicinal chemistry due to their promising potential as pharmaceutical agents. These molecular entities serve as critical scaffolds within numerous natural products, including curacin A, thiangazole, and mirabazole, and play a vital role in a wide array of physiological reactions. Their pharmacological versatility encompasses anti-HIV, neurological, anti-cancer, and antibiotic activities. Over the course of recent decades, researchers have extensively explored and developed analogs of these compounds, uncovering compelling therapeutic properties such as antioxidant, anti-tumor, anti-microbial, and anti-inflammatory effects. Consequently, thiazoline-based compounds have emerged as noteworthy targets for synthetic endeavors. In this review, we provide a comprehensive summary of recent advancements in the synthesis of thiazolines and thiazoline-based derivatives, along with an exploration of their diverse potential applications across various scientific domains.

Oxidative stress in Alzheimer's disease: current knowledge of signaling pathways and therapeutics.

Alzheimer's disease's pathophysiology is still a conundrum. Growing number of evidences have elucidated the involvement of oxidative stress in the pathology of AD rendering it a major target for therapeutic development. Reactive oxygen species (ROS) generated by altered mitochondrial function, dysregulated electron transport chain and other sources elevate aggregated Aß and neurofibrillary tangles which further stimulating the production of ROS. Oxidative stress induced damage to lipids, proteins and DNA result in neuronal death which leads to AD. In addition, oxidative stress induces apoptosis that is triggered by the modulation of ERK1/2 and Nrf2 pathway followed by increased GSK-3ß expression and decreased PP2A activity. Oxidative stress exaggerates disease condition by interfering with various signaling pathways like RCAN1, CREB/ERK, Nrf2, PP2A, NFκB and PI3K/Akt. Studies have reported the role of TNF-α in oxidative stress stimulation that has been regulated by drugs like etanercept increasing the level of anti-oxidants. Other drugs like pramipexole, memantine, carvedilol, and melatonin have been reported to activate CREB/RCAN1 and Nrf2 pathways. In line with this, epigallocatechin gallate and genistein also target Nrf2 and CREB pathway leading to activation of downstream pathways like ARE and Keap1 which ameliorate oxidative stress condition. Donepezil and resveratrol reduce oxidative stress and activate AMPK pathway along with PP2A activation thus promoting tau dephosphorylation and neuronal survival. This study describes in detail the role of oxidative stress in AD, major signaling pathways involving oxidative stress induced AD and drugs under development targeting these pathways which may aid in therapeutic advances for AD.

Tackling municipal solid waste crisis in India: Insights into cutting-edge technologies and risk assessment.

Municipal Solid Waste (MSW) management is a pressing global concern, with increasing interest in Waste-to-Energy Technologies (WTE-T) to divert waste from landfills. However, WTE-T adoption is hindered by financial uncertainties. The economic benefits of MSW treatment and energy generation must be balanced against environmental impact. Integrating cutting-edge technologies like Artificial Intelligence (AI) can enhance MSW management strategies and facilitate WTE-T adoption. This review paper explores waste classification, generation, and disposal methods, emphasizing public awareness to reduce waste. It discusses AI's role in waste management, including route optimization, waste composition forecasting, and process parameter optimization for energy generation. Various energy production techniques from MSW, such as high-solids anaerobic digestion, torrefaction, plasma pyrolysis, incineration, gasification, biodegradation, and hydrothermal carbonization, are examined for their advantages and challenges. The paper emphasizes risk assessment in MSW management, covering chemical, mechanical, biological, and health-related risks, aiming to identify and mitigate potential adverse effects. Electronic waste (E-waste) impact on human health and the environment is thoroughly discussed, highlighting the release of hazardous substances and their contribution to air, soil, and water pollution. The paper advocates for circular economy (CE) principles and waste-to-energy solutions to achieve sustainable waste management. It also addresses complexities and constraints faced by developing nations and proposes strategies to overcome them. In conclusion, this comprehensive review underscores the importance of risk assessment, the potential of AI and waste-to-energy solutions, and the need for sustainable waste management to safeguard public health and the environment.

A novel hybrid model integrating MFCC and acoustic parameters for voice disorder detection.

Voice is an essential component of human communication, serving as a fundamental medium for expressing thoughts, emotions, and ideas. Disruptions in vocal fold vibratory patterns can lead to voice disorders, which can have a profound impact on interpersonal interactions. Early detection of voice disorders is crucial for improving voice health and quality of life. This research proposes a novel methodology called VDDMFS [voice disorder detection using MFCC (Mel-frequency cepstral coefficients), fundamental frequency and spectral centroid] which combines an artificial neural network (ANN) trained on acoustic attributes and a long short-term memory (LSTM) model trained on MFCC attributes. Subsequently, the probabilities generated by both the ANN and LSTM models are stacked and used as input for XGBoost, which detects whether a voice is disordered or not, resulting in more accurate voice disorder detection. This approach achieved promising results, with an accuracy of 95.67%, sensitivity of 95.36%, specificity of 96.49% and f1 score of 96.9%, outperforming existing techniques.

Artificial Intelligence and Machine Learning in Pharmacological Research: Bridging the Gap Between Data and Drug Discovery.

Artificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.

Probing interaction of atherogenic lysophosphatidylcholine with functionalized graphene nanosheets: theoretical modelling and experimental validation.

CONTEXT: The potential of graphene derivatives for theranostic applications depends on their compatibility with cellular and biomolecular components. Lysophosphatidylcholine (LPC), a lipid component present in oxidized low-density lipoproteins, microvesicles and free circulation in blood, plays a critical role in the pathophysiology of various diseases. Using density functional theory-based methods, we systematically investigated the interaction of atherogenic LPC molecule with different derivatives of graphene, including pristine graphene, graphene with defect, N-doped graphene, amine-functionalized graphene, various graphene oxides and hydroxylated graphene oxides. We observed that the adsorption of LPC on graphene derivatives is highly selective based on the orientation of the functional groups of LPC interacting with the surface of the derivatives. Hydroxylated graphene oxide exhibited the strongest interaction with LPC with adsorption energy of - 2.1 eV due to the interaction between the hydroxyl group on graphene and the phosphate group of LPC. The presence of aqueous medium further enhanced this interaction indicating favourable adsorption of LPC and graphene oxide in biological systems. Such strong interaction leads to substantial change in the electronic structure of the LPC molecule, which results in the activation of this molecule. In contrast, amine-modified graphene showed the least interaction. These theoretical results are in line with our experimental fluorescence spectroscopic data of LPC/1-anilino-8-napthalene sulfonic acid complex. Our present comprehensive investigation employing both theoretical and experimental methods provides a deeper understanding of graphene-lipid interaction, which holds paramount importance in the design and fabrication of graphene-based nanomaterials for biomedical applications. METHODS: In this study, we employed the density functional theory-based methods to investigate the electronic and structural properties of graphene derivatives and LPC molecule using the Quantum Espresso package. The exchange-correlation functional was described within generalized gradient approximation (GGA) as parameterized by Perdew, Burke and Ernzerhof (PBE). The valence electrons were represented using plane wave basis sets. `The Grimme's dispersion method was used to include the van der Waals dispersion correction.

Platelet-derived microvesicles induce intracellular calcium mobilization in human platelets.

Platelet-derived microvesicles (PMVs) represent a significant proportion of microvesicles in circulation and have been linked to various pathophysiological complications. Recent research suggests that PMVs carry significant amounts of cargo that can affect cellular functions by influencing calcium oscillations in target cells. As calcium is involved in multiple cellular processes, including hemostasis and thrombosis, this study aimed to investigate the impact of PMVs on platelet calcium mobilization. The study found that PMVs increase platelet intracellular calcium levels via both intracellular storage and extracellular space in a dose-dependent manner. The study highlighted the critical role of the dense tubular system, acidic vacuoles, mitochondrial stores, and store-operated calcium entry (SOCE) in PMV-mediated calcium release in human platelets. Moreover, the study revealed that PMV-induced calcium rise in platelets does not occur via sarcoendoplasmic reticulum calcium ATPase, and extracellular calcium addition further increases the calcium level in platelets, demonstrating the involvement of SOCE. These findings provide insights into the platelet stimulation signaling mechanisms and contributes to our understanding of platelet and cell behavior when exposed to PMV-rich environments.

Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases.

The blood platelet plays an important role but often remains under-recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease-activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant-based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area.

All That We Need to Know About the Current and Past Outbreaks of Monkeypox: A Narrative Review.

Monkeypox is a rare, zoonotic viral illness that was initially endemic mainly to Africa. The virus later spread to non-African countries and, in 2022, it exploded on a global scale, with an unprecedented number of cases. The rapid, multi-country transmission, primarily in men who have sex with men (MSM), and evolving clinical manifestations and demographic traits of the current outbreak have raised serious concerns among the international health community. An in-depth inquiry into the past and present outbreaks are required, especially when contrasting features are witnessed across countries and outbreaks. This narrative review aims to summarize the evolution in the epidemiology, clinical features, mode of transmission, and management protocol of human monkeypox infection (H-MPVX) over the decades. For a detailed characterization of the novelties associated with the current outbreak that would facilitate the accurate dissemination of information and policy-making, we performed a thorough literature search for MPVX infection on PubMed, Google Scholar, and Science Direct, using appropriate keywords to choose relevant articles.

A Systematic Review of 5110 Cases of Monkeypox: What Has Changed Between 1970 and 2022?

The recent monkeypox (MPVX) outbreak has been characterized by an unprecedented increase in cases, unlike any other outbreaks in the past. The disease pattern and transmissibility are also different from previous outbreaks. This systematic review aimed to evaluate whether the current outbreak has significant contrasting features from the previous ones, necessitating changes in prevention and control guidelines. A thorough literature search related to MPVX infection was performed on the online databases PubMed, Google Scholar, and ScienceDirect using appropriate keywords "MPVX", "men who have sex with men (MSM)", "transmission", and "smallpox vaccination", for choosing relevant articles from the inception of MPVX in 1970 to August 31, 2022. We identified 5110 cases of MPVX, documented in 63 articles on MPVX. We discovered that the median age of MPVX infection has slowly increased since its inception, and currently, it is more common in adults. Compared to previous outbreaks, a significantly greater male preponderance is witnessed in the current outbreak. Only 238 (4.65%) out of the 5110 evaluated patients were vaccinated with the smallpox vaccine in our review. There were 107 mortalities, most of which were children below the age of 10 years. Out of the 1534 cases identified in 2022, 1134 (73.92%) patients admitted that they had been involved in sexual relations within the last 21 days (MSM/gay/bisexual). We found that in contrast to previous outbreaks, human-to-human transmission is more common in this outbreak, with most cases having no link with endemic countries. There are evolving traits and undetected transmission modes of MPVX infection that require new disease mitigation strategies.

Rhizospheric microbial consortium of Lilium lancifolium Thunb. causes lily root rot under continuous cropping system.

Tiger lily (Lilium lancifolium Thunb.) is a cash crop with a long history of cultivation in China. Its roots have long been used as a valuable component of Chinese medicine. Continuous cropping, the conventional planting approach for tiger lily, often leads to severe root rot disease, but it is not yet clear how this planting method leads to root rot. In this study, we analyzed the rhizosphere microbiome and predicted microbial protein function in tiger lily planted with the continuous cropping method in three different geological types of soil. In order to explore the specific rhizosphere microbiota triggering root rot disease, tiger lily was compared to maize grown in a similar system, which showed no disease development. An analysis of the chemical elements in the soil revealed that the Pseudomonas and Streptomyces genera, with pathogenic functions, were dominant in the tiger lily rhizosphere. The lower soil pH of tiger lily compared to maize supports the accumulation of pathogenic bacteria in the tiger lily rhizosphere. Meanwhile, we discovered that bacteria of the Flavobacterium genus, with their predicted phosphate transport function, specifically accumulated in the maize rhizosphere. Our findings suggest that Pseudomonas and Streptomyces bacteria may result in continuous cropping-induced root rot disease in tiger lily and that Flavobacterium could serve to protect maize from pathogenic bacteria.

ESTIMATION OF PERSONAL DOSE EQUIVALENT HP(0.07) USING CASO4:DY TEFLON DISC-BASED EXTREMITY DOSEMETER.

The radiation workers in India use extremity dosemeter in occupational areas where there is likelihood of receiving significant dose to extremities of the body. Algorithm used for the estimation of whole body dose and extremity dose of wrist are same and is based on slab phantom calibration. However, internationally, different phantoms are recommended for calibration of dosemeter used for extremity and whole body. The recommended quantity for estimation of dose to extremity is the personal dose equivalent Hp(0.07) at 0.07 mm depth. In light of this, an algorithm was developed for estimation of wrist dose in terms of Hp(0.07) based on calibration performed on ISO recommended pillar phantom. Performance of the dosemeter for the estimation of Hp(0.07) with new algorithm was carried out at different angular exposures of photon beams and mixed field of photon and beta. Comparison of results obtained for two types of ISO phantoms (slab and pillar) is also performed for photon beams to highlight the uncertainty caused due to the use of the slab phantom. In case of beta radiation, it was found that the size and shape of the phantom has very little influence in the response of the dosemeter. Performance of the dosemeter using ISO slab and ISO pillar phantoms for beta radiation using the prevalent algorithm was carried out and found to be within the uncertainty limits laid down by ISO except at angle 60°.

Plant latent defense response to microbial non-pathogenic factors antagonizes compatibility.

Unlike microbe-associated molecular patterns (MAMPs) that are readily targeted by host immunity, microbial non-pathogenic factors (NPFs) appear negligible as they do not elicit defense. Little is known about whether and how NPFs may be monitored by hosts to control compatibility. Herein, a forward genetic screening isolated an Arabidopsis mutant with a loss of plant-rhizobacteria mutualism, leading to the disclosure of a plant latent defense response (LDR) to NPFs. The activation of LDR in the mutant, named rol1 for regulator of LDR 1, is triggered by several non-pathogenic volatile organic compounds and antagonizes plant compatibility with the beneficial bacterium Bacillus amyloliquefaciens GB03. The activation of LDR in rol1 is mediated through the prokaryotic pathway of chloroplastic lipid biosynthesis. The rol1 root microbiome showed a reduced proportion of the Bacillaceae family. We propose that, parallel to the forefront immunity to MAMPs, LDR to certain NPFs provides a hidden layer of defense for controlling compatibility with commensal or beneficial microbes.

Tobacco smoking habits and nicotine dependence among the college students of University of Delhi, India.

Background: According to the report on tobacco control in India, tobacco use causes eight to nine lakh deaths annually in India. Tobacco use is on the rise among youngsters especially the college students. The Government of India has made a mandatory display of pictorial health warnings for both smoking and smokeless forms of tobacco products under the Cigarettes and Other Tobacco Product Act, 2003. The objective of the present study was to assess the prevalence of tobacco smoking and to assess nicotine dependence among the college students of the University of Delhi. Methods: A cross-sectional study was conducted among 400 college students of Delhi University from October to December 2019. A semi-structured self-administered questionnaire method was used to collect data on smoking; pictorial warnings and Fragerstrom criteria were used to assess nicotine dependence. Result: Out of the 400 study participants 92 (23%) participants were ever smokers. Among 62 current smokers, the mean age (±SD) of initiation of smoking was 17.3 years (±2.07), median (interquartile range [IQR]) number of cigarettes smoked per day was 3 (2-6), a majority (80.7%) used to smoke after 30 min of waking up in the morning, majority (59.7%) had low nicotine dependence. About half of the past smokers 47% (14 out of 30) and the current smokers 58% (36 out of 62) told that they had no effect of pictorial warning for quitting or decreasing smoking. Conclusion: The present study revealed the tobacco smoking pattern among college students of Delhi. The majority of smokers and non-smokers perceived that pictorial warning is ineffective in driving to quit smoking.

Noise-Activated Fast Locomotion of DNA through the Frictional Landscape of Nanoporous Gels.

It is hypothesized that nonlinear solid friction between the gel matrix and DNA molecules inhibits the motion of DNA through the nanopores of the gel during electrophoresis. In this article, it is demonstrated that external noise can alleviate the effect of solid friction, thus enhancing the mobility of DNA in an electrophoretic setting. In the presence of noise, the mobility of DNA increases by more than ∼113% compared to conventional electrophoresis. Although at a high power of noise, DNA exhibits Arrhenius kinetics, at a low power of noise, super-Arrhenius kinetics suggests the collective behavior of the activated motion of DNA molecules. A stochastic simulation following modified Langevin dynamics with the asymmetric pore size distribution of the agarose gel successfully predicts the mobility of DNA molecules and reveals the salient features of the overall dynamics. This "noise lubricity" may have a broader applicability from molecular to macroscopic locomotion.

Flavonoid-attracted Aeromonas sp. from the Arabidopsis root microbiome enhances plant dehydration resistance.

Flavonoids are stress-inducible metabolites important for plant-microbe interactions. In contrast to their well-known function in initiating rhizobia nodulation in legumes, little is known about whether and how flavonoids may contribute to plant stress resistance through affecting non-nodulating bacteria. Here we show that flavonoids broadly contribute to the diversity of the Arabidopsis root microbiome and preferentially attract Aeromonadaceae, which included a cultivable Aeromonas sp. H1 that displayed flavonoid-induced chemotaxis with transcriptional enhancement of flagellum biogenesis and suppression of fumarate reduction for smooth swims. Strain H1 showed multiple plant-beneficial traits and enhanced plant dehydration resistance, which required flavonoids but not through a sudden "cry-for-help" upon stress. Strain H1 boosted dehydration-induced H2O2 accumulation in guard cells and stomatal closure, concomitant with synergistic induction of jasmonic acid-related regulators of plant dehydration resistance. These findings revealed a key role of flavonoids, and the underlying mechanism, in mediating plant-microbiome interactions including the bacteria-enhanced plant dehydration resistance.

Species Composition and Diversity Dynamics of Actinomycetes in Arid and Semi-arid Salt Basins of Rajasthan.

Species composition and diversity dynamics of the actinomycetes was studied in five salt basins of arid and semi-arid areas of Rajasthan, India. A novel approach integrating molecular (16S rRNA gene) and diversity indices was applied to reveal species composition and diversity dynamics. Fifty-three actinomycetes isolates were isolated from five arid and semi-arid salt basins. Molecular characterization resulted in the identification of actinomycetes species belonging to three genera namely, Streptomyces, Nocardiopsis, and Actinoalloteichus. The diversity study among actinomycetes species validates their universal occurrence in arid and semi-arid regions of Rajasthan. The species N. dassonvillei subsp. albirubida was omnipresent in all the five salt basins but its relative manifestation was not static across habitats. The study revealed that three species N. chromatogenes, S. durbertensis, and S. mangrovicola are being reported for the first time from India. The maximum species of actinomycetes were recorded from Pachpadra (14) and the minimum from Didwana area (6). This study not only documents the hitherto wealth of actinomycetes species in arid and semi-arid salt basins of Rajasthan but also reveals the composition and diversity dynamics of actinomycetes.