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We evaluate different Neural Radiance Field (NeRF) techniques for the 3D reconstruction of plants in varied environments, from indoor settings to outdoor fields. Traditional methods usually fail to capture the complex geometric details of plants, which is crucial for phenotyping and breeding studies. We evaluate the reconstruction fidelity of NeRFs in 3 scenarios with increasing complexity and compare the results with the point cloud obtained using light detection and ranging as ground truth. In the most realistic field scenario, the NeRF models achieve a 74.6% F1 score after 30 min of training on the graphics processing unit, highlighting the efficacy of NeRFs for 3D reconstruction in challenging environments. Additionally, we propose an early stopping technique for NeRF training that almost halves the training time while achieving only a reduction of 7.4% in the average F1 score. This optimization process substantially enhances the speed and efficiency of 3D reconstruction using NeRFs. Our findings demonstrate the potential of NeRFs in detailed and realistic 3D plant reconstruction and suggest practical approaches for enhancing the speed and efficiency of NeRFs in the 3D reconstruction process., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Muhammad Arbab Arshad et al.)

Carbon-based nanodots have garnered recent interest for their simple synthesis and versatile utility, ranging from biomedical to (opto) electronic applications, evolving into a tunable and biocompatible material. Here, for the first time, a biochar (lotus leaf) derived carbon nanodots was synthesized through hydrothermal carbonization. The synthesized hollow spherical biochar was engineered via functionalization by grafting -SO 3 H active sites. The attained catalyst was broadly analyzed by XRD, FTIR, TGA, BET, SEM-EDX, TEM, and XPS analysis after which it was applied for the acetalization reaction of crude glycerol (a biodiesel by-product) to form solketal, a potential fuel additive to valorize the large waste stream generated from biodiesel industry. Employing the RSM-CCD methodology, the experimental matrix was executed, and subsequent data were scrutinized through multiple regressions to model a quadratic equation. Under specific reaction parameters-a reaction duration of 14 min, a molar ratio of 7.5:1, and a catalyst loading of 5.7 wt.%, maximum solketal yield (95.7%) was attained through the ultrasonication method. Finally, to conclude, life cycle cost analysis (LCCA) for solketal production was studied here which determined the overall cost of solketal production per kilogram to be 0.719 USD ($), indicating high commercial applicability., (© 2024. The Author(s).)

Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. Results: Through a comprehensive literature review and the Integrated Medicinal Plant Phytochemistry and Therapeutics database (IMPPAT), we identified 33 bioactive molecules from P. longum . Subsequent analyses employing tools such as SwissTargetPrediction, SuperPred, and DIGEP-Pred facilitated the isolation of 676 potential targets, among which 72 intersected with 666 lung cancer-associated genetic markers identified through databases including the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards. Further validation through protein-protein interaction (PPI) networks, gene ontology, pathway analyses, boxplots, and overall survival metrics underscored the therapeutic potential of compounds such as 7-epi-eudesm-4(15)-ene-1β, demethoxypiplartine, methyl 3,4,5-trimethoxycinnamate, 6-alpha-diol, and aristolodione. Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Let G be a connected graph with d i a m ( G ) . Then d ( u , v ) indicates the distance of u and v in G . For any pair of distinct vertices u , v of G , mapping from c : V ( G ) → N such that d G ( u , v ) + | c ( u ) - c ( v ) | ≥ d i a m ( G ) + 1 . The maximum label assigned to any vertex of G under a radio labeling c is known as the span of c . The radio number r n ( G ) of G is defined as the minimum span among all possible radio labelings of G . This paper aims to determine the radio number r n ( c ) for specific constructed families of graphs with diameter 3, such as P 2 2 ( N ( m , n ) ) , K 3 , m ( K n c ) , K 3 , m ( n P 3 ) , K 3 , 3 ( 2 K 1 , n ) , and K 5 ( F 3 n ) ., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ravi Sankar Jeyaraj reports article publishing charges was provided by 10.13039/501100004728Vellore Institute of Technology. Ravi Sankar Jeyaraj reports a relationship with Vellore Institute of Technology that includes: non-financial support. Ravi Sankar Jeyaraj has patent pending to No Patent or Numbers. The authors declare that they have no conflict of interest., (© 2024 The Authors.)

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Muthuramalingam, Jeyasri, Varadharajan, Priya, Dhanapal, Shin, Thiruvengadam, Ramesh, Krishnan, Omosimua, Sathyaseelan and Venkidasamy.)

Recently, nanoparticles have received considerable attention owing to their efficiency in overcoming the limitations of traditional chemotherapeutic drugs. In our study, we synthesized a vanillic acid nanocomposite using both chitosan and silver nanoparticles, tested its efficacy against lung cancer cells, and analyzed its antimicrobial effects. We used several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to determine the stability, morphological characteristics, and properties of the biosynthesized vanillic acid nanocomposites. Furthermore, the vanillic acid nanocomposites were tested for their antimicrobial effects against Escherichia coli and Staphylococcus aureus , and Candida albicans . The data showed that the nanocomposite effectively inhibited microbes, but its efficacy was less than that of the individual silver and chitosan nanoparticles. Moreover, the vanillic acid nanocomposite exhibited anticancer effects by increasing the expression of pro-apoptotic proteins (BAX, Casp3, Casp7, cyt C, and p53) and decreasing the gene expression of Bcl-2. Overall, vanillic acid nanocomposites possess promising potential against microbes, exhibit anticancer effects, and can be effectively used for treating diseases such as cancers and infectious diseases.

Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.

Ataxin-2 (ATXN2) is a gene implicated in spinocerebellar ataxia type II (SCA2), amyotrophic lateral sclerosis (ALS) and Parkinsonism. The encoded protein is a therapeutic target for ALS and related conditions. ATXN2 (or Atx2 in insects) can function in translational activation, translational repression, mRNA stability and in the assembly of mRNP-granules, a process mediated by intrinsically disordered regions (IDRs). Previous work has shown that the LSm (Like-Sm) domain of Atx2, which can help stimulate mRNA translation, antagonizes mRNP-granule assembly. Here we advance these findings through a series of experiments on Drosophila and human Ataxin-2 proteins. Results of Targets of RNA Binding Proteins Identified by Editing (TRIBE), co-localization and immunoprecipitation experiments indicate that a polyA-binding protein (PABP) interacting, PAM2 motif of Ataxin-2 may be a major determinant of the mRNA and protein content of Ataxin-2 mRNP granules. Experiments with transgenic Drosophila indicate that while the Atx2-LSm domain may protect against neurodegeneration, structured PAM2- and unstructured IDR- interactions both support Atx2-induced cytotoxicity. Taken together, the data lead to a proposal for how Ataxin-2 interactions are remodelled during translational control and how structured and non-structured interactions contribute differently to the specificity and efficiency of RNP granule condensation as well as to neurodegeneration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Petrauskas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plants encounter a variety of beneficial and harmful insects during their growth cycle. Accurate identification (i.e., detecting insects' presence) and classification (i.e., determining the type or class) of these insect species is critical for implementing prompt and suitable mitigation strategies. Such timely actions carry substantial economic and environmental implications. Deep learning-based approaches have produced models with good insect classification accuracy. Researchers aim to implement identification and classification models in agriculture, facing challenges when input images markedly deviate from the training distribution (e.g., images like vehicles, humans, or a blurred image or insect class that is not yet trained on). Out-of-distribution (OOD) detection algorithms provide an exciting avenue to overcome these challenges as they ensure that a model abstains from making incorrect classification predictions on images that belong to non-insect and/or untrained insect classes. As far as we know, no prior in-depth exploration has been conducted on the role of the OOD detection algorithms in addressing agricultural issues. Here, we generate and evaluate the performance of state-of-the-art OOD algorithms on insect detection classifiers. These algorithms represent a diversity of methods for addressing an OOD problem. Specifically, we focus on extrusive algorithms, i.e., algorithms that wrap around a well-trained classifier without the need for additional co-training. We compared three OOD detection algorithms: (a) maximum softmax probability, which uses the softmax value as a confidence score; (b) Mahalanobis distance (MAH)-based algorithm, which uses a generative classification approach; and (c) energy-based algorithm, which maps the input data to a scalar value, called energy. We performed an extensive series of evaluations of these OOD algorithms across three performance axes: (a) Base model accuracy: How does the accuracy of the classifier impact OOD performance? (b) How does the level of dissimilarity to the domain impact OOD performance? (c) Data imbalance: How sensitive is OOD performance to the imbalance in per-class sample size? Evaluating OOD algorithms across these performance axes provides practical guidelines to ensure the robust performance of well-trained models in the wild, which is a key consideration for agricultural applications. Based on this analysis, we proposed the most effective OOD algorithm as wrapper for the insect classifier with highest accuracy. We presented the results of its OOD detection performance in the paper. Our results indicate that OOD detection algorithms can significantly enhance user trust in insect pest classification by abstaining classification under uncertain conditions., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Mojdeh Saadati et al.)

A methodological approach based on rare earth elements analysis was developed to observe human activities in the stratigraphic sequence of Alagankulam. The site was one of the main ancient ports in south-eastern India and one of the transoceanic connecting points between East and West during the Classical Period. The sampled sediments where collected from vertical profiles, areas with traces of firing activities and filled deposits. Major, minor and trace element concentrations were measured by the means of spectroscopic and spectrometric techniques. Data from multielemental analysis were then cross-referenced together with archaeological evidence to map the variability within the site and its association with the detected anthropic activities. The matching of the interpretation of the archaeological record and the analytical data has allowed a combined mapping of visible and invisible traces of human activities in the site, giving a deeper insight of the Alagankulam occupational history., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction : Breast cancer results from tissue degradation caused by environmental and genetic factors that affect cells in the body. Matrix metalloproteinases, such as MMP-2 and MMP-9, are considered potential putative markers for tumor diagnosis in clinical validation due to their easy detection in body fluids. In addition, recent reports have suggested multiple roles for MMPs, rather than simply degeneration of the extracellular matrix, which comprises mobilizing growth factors and processing surface molecules. Methods : In this study, the chemotherapeutic effects of anthraquinone (AQ) extracted from edible mushrooms ( Pleurotus ostreatus Jacq. ex Fr.) cells was examined in MCF-7 breast cancer cells. The cytotoxic potential and oxidative stress induced by purified anthraquinone were assessed in MCF-7 cells using MTT and ROS estimation assays. Gelatin Zymography, and DNA fragmentation assays were performed to examine MMP expression and apoptotic induction in the MCF-7 cells treated with AQ. The genes crucial for mutations were examined, and the mutated RNA knockout plausibility was analyzed using the CRISPR spcas9 genome editing software. Results : MCF-7 cells were attenuated in a concentration-dependent manner by the administration of AQ purified from P. ostreatus compared with the standard anticancer drug paclitaxel. AQ supplementation decreased oxidative stress and mitochondrial impairment in MCF-7 cells. Treatment with AQ and AQ with paclitaxel consistently decreased the expression of crucial marker genes such as MMP2 and MMP9 . The mutated genes MMP2 , MMP7 , and MMP9 were assessed and observed to reveal four putative gene knockdown potentials for breast cancer treatment. Conclusions : The synergistic application of AQ and paclitaxel exerted a strong inhibitory effect on the MCF-7 breast cancer cells. Extensive studies are imperative to better understand the action of bioactive mixes on the edible oyster fungus P. ostreatus . The gene knockout potential detected by CRISPR SpCas9 will aid in elite research into anticancer treatments., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Regular monitoring of blood glucose levels is essential for the management of diabetes and the development of appropriate treatment protocols. The conventional blood glucose (BG) testing have an intrusive technique to prick the finger and it can be uncomfortable when it is a regular practice. Intrusive procedures, such as fingerstick testing has negatively influencing patient adherence. Diabetic patients now have an exceptional improvement in their quality of life with the development of cutting-edge sensors and healthcare technologies. intensive care unit (ICU) and pregnant women also have facing challenges including hyperglycemia and hypoglycemia. The worldwide diabetic rate has incited to develop a wearable and accurate non-invasive blood glucose monitoring system. This research developed an Internet of Things (IoT) - enabled wearable blood glucose monitoring (iGM) system to transform diabetes care and enhance the quality of life. The TTGOT-ESP32 IoT platform with a red and near-infrared (R-NIR) spectral range for blood glucose measurement has integrated into this wearable device. The primary objective of this gadget is to provide optimal comfort for the patients while delivering a smooth monitoring experience. The iGM gadget is 98.82 % accuracy when used after 10 hours of fasting and 98.04 % accuracy after 2 hours of breakfast. The primary objective points of the research were continuous monitoring, decreased risk of infection, and improved quality of life. This research contributes to the evolving field of IoT-based healthcare solutions by streaming real-time glucose values on AWS IoT Core to empower individuals with diabetes to manage their conditions effectively. The iGM Framework has a promising future with the potential to transform diabetes management and healthcare delivery., (© 2024. The Author(s).)

Soil pollution from various anthropogenic and natural activities poses a significant threat to the environment and human health. This study explored the sources and types of soil pollution and emphasized the need for innovative remediation approaches. Nanotechnology, including the use of nanoparticles, is a promising approach for remediation. Diverse types of nanomaterials, including nanobiosorbents and nanobiosurfactants, have shown great potential in soil remediation processes. Nanotechnology approaches to soil pollution remediation are multifaceted. Reduction reactions and immobilization techniques demonstrate the versatility of nanomaterials in mitigating soil pollution. Nanomicrobial-based bioremediation further enhances the efficiency of pollutant degradation in agricultural soils. A literature-based screening was conducted using different search engines, including PubMed, Web of Science, and Google Scholar, from 2010 to 2023. Keywords such as "soil pollution, nanotechnology, nanoremediation, heavy metal remediation, soil remediation" and combinations of these were used. The remediation of heavy metals using nanotechnology has demonstrated promising results and offers an eco-friendly and sustainable solution to address this critical issue. Nanobioremediation is a robust strategy for combatting organic contamination in soils, including pesticides and herbicides. The use of nanophytoremediation, in which nanomaterials assist plants in extracting and detoxifying pollutants, represents a cutting-edge and environmentally friendly approach for tackling soil pollution., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Serum titers of SARS-CoV-2-neutralizing antibodies (nAbs) correlate well with protection from symptomatic COVID-19 but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are lifelong after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We, therefore, sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain, and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated the potent induction of high titer nAbs in measles-immune mice and confirmed the significant contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin display of the SARS-CoV-2 spike glycoprotein. In animals primed and boosted with a measles virus (MeV) vaccine encoding the ancestral SARS-CoV-2 spike, high-titer nAb responses against ancestral virus strains were only weakly cross-reactive with the Omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the Omicron BA.1 spike, antibody titers to both ancestral and Omicron strains were robustly elevated, and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that by engineering the antigen, we can develop potent measles-based vaccine candidates against SARS-CoV-2.IMPORTANCEAlthough the live-attenuated measles virus (MeV) is one of the safest and most efficacious human vaccines, a measles-vectored COVID-19 vaccine candidate expressing the SARS-CoV-2 spike failed to elicit neutralizing antibody (nAb) responses in a phase-1 clinical trial, especially in measles-immune individuals. Here, we constructed a comprehensive panel of MeV-based COVID-19 vaccine candidates using a MeV with extensive modifications on the envelope glycoproteins (MeV-MR). We show that artificial trimerization of the spike is critical for the induction of nAbs and that their magnitude can be significantly augmented when the spike protein is synchronously fused to a dodecahedral scaffold. Furthermore, preexisting measles immunity did not abolish heterologous immunity elicited by our vector. Our results highlight the importance of antigen optimization in the development of spike-based COVID-19 vaccines and therapies., Competing Interests: As of July 2021, M.Á.M.-A. was appointed as a scientific director at Vyriad Inc., a clinical-stage biotechnology company developing oncolytic viruses for the treatment of cancers. M.Á.M.-A. and S.J.R. are inventors on a patent application (US Patent App. 17/518,268) filed by the Mayo Clinic relating to the MeV-MR vector that has been licensed to Vyriad Inc. The Mayo Clinic has filed an invention report for the spike protein miniferritin nanoparticle described in this manuscript. The Mayo Clinic may stand to gain financially from the successful outcome of this research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest Policies. The laboratory of S.J.R. has received research support from Vyriad Inc. M.S. has received research support from ArgenX N.V. and Moderna. The laboratory of A.G.-S. has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Merck, and Nanocomposix, and A.G.-S. has consulting agreements involving cash and/or stock for the following companies: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, Synairgen, and Pfizer.

Introduction: Broccoli is a cruciferous vegetable that has been shown to have numerous potential therapeutic benefits because of its bioactive compounds. Methods: In this study, we compared the bioactive efficacy of cooked and uncooked (fresh) stems and florets of broccoli extracted with three different solvents: acetonitrile, methanol, and aqueous extracts. The extraction yield and antioxidant and antibacterial potential of different broccoli extracts were examined. Results: Fresh and boiled floret stem extracts increased the extraction yield. The extraction yields were higher for the methanol and acetonitrile extracts than for the aqueous extracts. The antioxidant efficacy of the different extracts was studied using ABTS, DPPH, and metal ion reduction assays. The acetonitrile and aqueous extracts exhibited higher antioxidant activities than the methanolic extracts in different antioxidant assays. In addition, increased antioxidant activity was observed in fresh florets and boiled broccoli stems. TPC and TFC contents were higher in the methanolic extracts than in the aqueous extracts. Similar to antioxidant activities, anti-inflammatory activities were found to be higher in the acetonitrile and aqueous extracts, particularly in boiled stems and fresh florets. Broccoli extracts have been shown to be active against Bacillus subtilis and moderately effective against Pseudomonas aeruginosa and Staphylococcus aureus . Conclusions: Acetonitrile and aqueous extraction of broccoli might be an ideal choice for extraction methods, which show increased extraction yield and antioxidant and anti-inflammatory potentials. Utilization of phytomolecules from natural sources is a promising alternative approach to synthetic drug development., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Pyrimidines have become an increasingly important core structure in many drug molecules over the past 60 years. This article surveys recent areas in which pyrimidines have had a major impact in drug discovery therapeutics, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article presents the synthesis of the medicinal agents and highlights the role of the biological target with respect to the disease model. Additionally, the biological potency, ADME properties and pharmacokinetics/pharmacodynamics (if available) are discussed. This survey attempts to demonstrate the versatility of pyrimidine-based drugs, not only for their potency and affinity but also for the improved medicinal chemistry properties of pyrimidine as a bioisostere for phenyl and other aromatic π systems. It is hoped that this article will provide insight to researchers considering the pyrimidine scaffold as a chemotype in future drug candidates in order to counteract medical conditions previously deemed untreatable.

Driven by a surge in global interest in natural products, macroalgae or seaweed, has emerged as a prime source for nutraceuticals and pharmaceutical applications. Characterized by remarkable genetic diversity and a crucial role in marine ecosystems, these organisms offer not only substantial nutritional value in proteins, fibers, vitamins, and minerals, but also a diverse array of bioactive molecules with promising pharmaceutical properties. Furthermore, macroalgae produce approximately 80% of the oxygen in the atmosphere, highlighting their ecological significance. The unique combination of nutritional and bioactive attributes positions macroalgae as an ideal resource for food and medicine in various regions worldwide. This comprehensive review consolidates the latest advancements in the field, elucidating the potential applications of macroalgae in developing nutraceuticals and therapeutics. The review emphasizes the pivotal role of omics approaches in deepening our understanding of macroalgae's physiological and molecular characteristics. By highlighting the importance of omics, this review also advocates for continued exploration and utilization of these extraordinary marine organisms in diverse domains, including drug discovery, functional foods, and other industrial applications. The multifaceted potential of macroalgae warrants further research and development to unlock their full benefits and contribute to advancing global health and sustainable industries.

Introduction: Surgical site infections (SSIs) following head and neck cancer surgery are very common postoperative sequelae. Delayed wound healing leads to a poor aesthetic outcome, delay in restarting oral intake, and delay in getting or starting adjuvant therapy. Antibiotic resistance is on the rise necessitating studies that use alternatives to combat the rising antibiotic resistance. Many plant compounds have been studied to explore the possibility. Neem ( Azadirachta indica ), a high medicinal value plant, possesses a vast array of phytocompounds, which are broadly grouped into isoprenoids and non-isoprenoids. These phytocompounds are crucial for its anti-inflammatory, antioxidant, antimicrobial, antipyretic, and various other pharmacological activities., Materials and Methods: In this study, we examined the impact of the extraction solvents on the bioactive potential of neem. Neem leaf samples were extracted with water and ethanol; followed by their biological activities like extraction yield, antioxidant, antimicrobial, and cytotoxicity studies were performed. The extraction yield was found to be higher in the ethanolic extract than in the aqueous extract, which also corroborates with increased antioxidant and antibacterial activity. Both the aqueous and ethanolic extracts of neem exhibited antibacterial activities against dental biofilm-producing pathogens like Staphylococcus aureus, Streptococcus mutans, Pseudomonas aeruginosa, and Escherichia coli. Results: Extraction yield was higher in the ethanolic extract of neem. Antioxidant activity was found to be higher in the ethanolic extract than in the aqueous extract. Neem extract has no toxicity, which was observed through hemolytic and zebrafish embryo toxicity assays. The ethanolic extract of neem was shown to be more effective against the Gram-positive and Gram-negative drug-resistant bacterial pathogen Discussion and conclusion: Thus, the utilization of neem extracts is certainly useful in controlling pathogenic bacterial growth in clinical applications. Further, a detailed mechanism of action of neem extract in bacterial growth inhibition at the molecular level is warranted to utilize their potential in disease management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, S et al.)

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC., (© 2023. The Author(s).)

Upon water loss, some organisms pause their life cycles and escape death. While widespread in microbes, this is less common in animals. Aedes mosquitoes are vectors for viral diseases. Aedes eggs can survive dry environments, but molecular and cellular principles enabling egg survival through desiccation remain unknown. In this report, we find that Aedes aegypti eggs, in contrast to Anopheles stephensi, survive desiccation by acquiring desiccation tolerance at a late developmental stage. We uncover unique proteome and metabolic state changes in Aedes embryos during desiccation that reflect reduced central carbon metabolism, rewiring towards polyamine production, and enhanced lipid utilisation for energy and polyamine synthesis. Using inhibitors targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of desiccation tolerance in Aedes eggs. The metabolic rewiring towards lipid breakdown and dependent polyamine accumulation confers resistance to desiccation. Furthermore, rapid lipid breakdown is required to fuel energetic requirements upon water reentry to enable larval hatching and survival upon rehydration. This study is fundamental to understanding Aedes embryo survival and in controlling the spread of these mosquitoes., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Prasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The increasing demand for food is the result of an increasing population. It is crucial to enhance crop yield for sustainable production. Recently, microRNAs (miRNAs) have gained importance because of their involvement in crop productivity by regulating gene transcription in numerous biological processes, such as growth, development and abiotic and biotic stresses. miRNAs are small, non-coding RNA involved in numerous other biological functions in a plant that range from genomic integrity, metabolism, growth, and development to environmental stress response, which collectively influence the agronomic traits of the crop species. Additionally, miRNA families associated with various agronomic properties are conserved across diverse plant species. The miRNA adaptive responses enhance the plants to survive environmental stresses, such as drought, salinity, cold, and heat conditions, as well as biotic stresses, such as pathogens and insect pests. Thus, understanding the detailed mechanism of the potential response of miRNAs during stress response is necessary to promote the agronomic traits of crops. In this review, we updated the details of the functional aspects of miRNAs as potential regulators of various stress-related responses in agronomic plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Samynathan, Venkidasamy, Shanmugam, Ramalingam and Thiruvengadam.)

Introduction: Globally, lung cancer is a highly harmful type of cancer. An efficient diagnosis system can enable pathologists to recognize the type and nature of lung nodules and the mode of therapy to increase the patient's chance of survival. Hence, implementing an automatic and reliable system to segment lung nodules from a computed tomography (CT) image is useful in the medical industry., Methods: This study develops a novel fully convolutional deep neural network (hereafter called DeepNet) model for segmenting lung nodules from CT scans. This model includes an encoder/decoder network that achieves pixel-wise image segmentation. The encoder network exploits a Visual Geometry Group (VGG-19) model as a base architecture, while the decoder network exploits 16 upsampling and deconvolution modules. The encoder used in this model has a very flexible structural design that can be modified and trained for any resolution based on the size of input scans. The decoder network upsamples and maps the low-resolution attributes of the encoder. Thus, there is a considerable drop in the number of variables used for the learning process as the network recycles the pooling indices of the encoder for segmentation. The Thresholding method and the cuckoo search algorithm determines the most useful features when categorizing cancer nodules., Results and Discussion: The effectiveness of the intended DeepNet model is cautiously assessed on the real-world database known as The Cancer Imaging Archive (TCIA) dataset and its effectiveness is demonstrated by comparing its representation with some other modern segmentation models in terms of selected performance measures. The empirical analysis reveals that DeepNet significantly outperforms other prevalent segmentation algorithms with 0.962 ± 0.023% of volume error, 0.968 ± 0.011 of dice similarity coefficient, 0.856 ± 0.011 of Jaccard similarity index, and 0.045 ± 0.005s average processing time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 M and S.)

Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta . Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17- and interferon-γ-producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.

Background and Objectives: Breast cancer is a significant type of cancer among women worldwide. Studies have reported the anti-carcinogenic activity of Hydrastis Canadensis (Goldenseal) in cancer cell lines. Hydrastis Canadensis could help eliminate toxic substances due to its anti-cancer, anti-inflammatory, and other properties. The design phase includes the identification of potential and effective molecules through modern computational techniques. Objective: This work aims to study Hydrastis Canadensis's effect in controlling hormone-independent breast cancer through in-silico analysis. Materials and Methods: The preliminary screening of reported phytochemicals includes biomolecular networking. Identifying functionally relevant phytochemicals and the respective target mutations/genes leads to selecting 3D proteins of the desired mutations being considered the target. Interaction studies have been conducted using docking. The kinetic and thermodynamic stability of complexes was studied through molecular dynamic simulation and MM-PBSA/GBSA analysis. Pharmacodynamic and pharmacokinetic features have been predicted. The mechanism-wise screening, functional enrichment, and interactional studies suggest that canadaline and Riboflavin effectively interact with the target proteins. Results: Hydrastis Canadensis has been identified as the effective formulation containing all these constituents. The phytoconstituents; Riboflavin and Canadensis showed good interaction with the targets of hormone-independent breast cancer. The complexes were found to be kinetically and thermodynamically stable. Conclusions: Hydrastis Canadensis has been identified as effective in controlling 'hormone-independent or basal-like breast cancer' followed by 'hormone-dependent breast cancer: Luminal A' and Luminal B.

Background and Aims: Induced prismatic effects due to poor fitting spectacle frames is a common problem, seen in most of the spectacle wearers and this improper fitting is often due to optical center demarcation on lenses and this error causes asthenopic symptoms and diplopia. However, these errors are most common in developing countries due to lack of awareness, hence a standardized regulation is required. The current study aimed to estimate the amount of prismatic effect that is induced due to the decentration of an optical center in ophthalmic lens., Methods: A quantitative cross-sectional study was conducted in single vision spectacle wearers ( N  = 120) with a mean age of 25 ± 5 years. The pupillometric evaluation was performed to mark the pupil center on the spectacle lens. A lensometry evaluation was done to mark the optic center of the spectacle lens. A comparison was made to note whether the optic center is aligned with pupillary center. Objective assessment was performed through Prentice's rule (P = cF) and subjective symptoms were assessed through a validated visual comfort questionnaire., Results: In this sample, around 57% of the individual with single vision glasses were not looking through the optic center and experiencing induced prismatic effect of -0.7 to 0.6 prism diopter, with mean decentration of 3.5 mm. Forty percent of the individuals with misaligned optic center showed asthenopic symptoms and visual discomfort., Conclusion: Optometrist should check quality of dispensing and visual performance before handing over the newly dispensed glasses to the patients., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the cellular antioxidant defense system at the posttranscriptional level. During oxidative stress, Nrf2 is released from its negative regulator Kelch-like ECH-associated protein 1 (Keap1) and binds to antioxidant response element (ARE) to transcribe antioxidative metabolizing/detoxifying genes. Various transcription factors like aryl hydrocarbon receptor (AhR) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) and epigenetic modification including DNA methylation and histone methylation might also regulate the expression of Nrf2. Despite its protective role, Keap1/Nrf2/ARE signaling is considered as a pharmacological target due to its involvement in various pathophysiological conditions such as diabetes, cardiovascular diseases, cancers, neurodegenerative diseases, hepatotoxicity and kidney disorders. Recently, nanomaterials have received a lot of attention due to their unique physiochemical properties and are also used in various biological applications, for example, biosensors, drug delivery systems, cancer therapy, etc. In this review, we will be discussing the functions of nanoparticles and Nrf2 as a combined therapy or sensitizing agent and their significance in various diseases such as diabetes, cancers and oxidative stress-mediated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis of indeterminate potential (CHIP) is frequent in aging and involves the expansion of mutated hematopoietic stem and progenitor cells (HSC/Ps) that leads to an increased risk of hematologic malignancy. However, the risk factors that contribute to CHIP-associated clonal hematopoiesis (CH) are poorly understood. Obesity induces a proinflammatory state and fatty bone marrow (FBM), which may influence CHIP-associated pathologies. We analyzed exome sequencing and clinical data for 47,466 individuals with validated CHIP in the UK Biobank. CHIP was present in 5.8% of the study population and was associated with a significant increase in the waist-to-hip ratio (WHR). Mouse models of obesity and CHIP driven by heterozygosity of Tet2, Dnmt3a, Asxl1, and Jak2 resulted in exacerbated expansion of mutant HSC/Ps due in part to excessive inflammation. Our results show that obesity is highly associated with CHIP and that a proinflammatory state could potentiate the progression of CHIP to more significant hematologic neoplasia. The calcium channel blockers nifedipine and SKF-96365, either alone or in combination with metformin, MCC950, or anakinra (IL-1 receptor antagonist), suppressed the growth of mutant CHIP cells and partially restored normal hematopoiesis. Targeting CHIP-mutant cells with these drugs could be a potential therapeutic approach to treat CH and its associated abnormalities in individuals with obesity.

Loss-of-function mutations in the DNA methyltransferase 3A (DNMT3A) are seen in a large number of patients with acute myeloid leukemia (AML) with normal cytogenetics and are frequently associated with poor prognosis. DNMT3A mutations are an early preleukemic event, which - when combined with other genetic lesions - result in full-blown leukemia. Here, we show that loss of Dnmt3a in hematopoietic stem and progenitor cells (HSC/Ps) results in myeloproliferation, which is associated with hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway. PI3Kα/β or the PI3Kα/δ inhibitor treatment partially corrects myeloproliferation, although the partial rescue is more efficient in response to the PI3Kα/β inhibitor treatment. In vivo RNA-Seq analysis on drug-treated Dnmt3a-/- HSC/Ps showed a reduction in the expression of genes associated with chemokines, inflammation, cell attachment, and extracellular matrix compared with controls. Remarkably, drug-treated leukemic mice showed a reversal in the enhanced fetal liver HSC-like gene signature observed in vehicle-treated Dnmt3a-/- LSK cells as well as a reduction in the expression of genes involved in regulating actin cytoskeleton-based functions, including the RHO/RAC GTPases. In a human PDX model bearing DNMT3A mutant AML, PI3Kα/β inhibitor treatment prolonged their survival and rescued the leukemic burden. Our results identify a potentially new target for treating DNMT3A mutation-driven myeloid malignancies.

Overall, combating food waste necessitates a multifaceted approach that includes education, infrastructure, and policy change. By working together to implement these strategies, we can help reduce the negative impacts of food waste and create a more sustainable and equitable food system. The sustained supply of nutrient-rich agrifood commodities is seriously threatened by inefficiencies caused by agricultural losses, which must be addressed. As per the statistical data given by the Food and Agriculture Organisation (FAO) of the United Nations, nearly 33.33% of the food that is produced for utilization is wasted and frittered away on a global level, which can be estimated as a loss of 1.3 billion metric tons per annum, which includes 30% cereals, 20% dairy products 35% seafood and fish, 45% fruits and vegetables, and 20% of meat. This review summarizes the various types of waste originating from various segments of the food industry, such as fruits and vegetables, dairy, marine, and brewery, also focusing on their potential for developing commercially available value-added products such as bioplastics, bio-fertilizers, food additives, antioxidants, antibiotics, biochar, organic acids, and enzymes. The paramount highlights include food waste valorization, which is a sustainable yet profitable alternative to waste management, and harnessing Machine Learning and Artificial Intelligence technology to minimize food waste. Detail of sustainability and feasibility of food waste-derived metabolic chemical compounds, along with the market outlook and recycling of food wastes, have been elucidated in this review.

Purpose: To investigate the quality of life (QoL) in a sample of color vision deficit (CVD) patients in India and how color vision deficiency affects them psychologically, economically, and in productivity related to their work and occupation., Methods: A descriptive and case-control study design using a questionnaire was conducted on N = 120 participants, of whom 60 were patients of CVD (52 male and eight female) who visited two eye facilities in Hyderabad between 2020 and 2021 and 60 were age-matched normal color vision participants who served as controls. We validated English-Telugu adapted version of CVD-QoL, developed by Barry et al. in 2017 (CB-QoL). The CVD-QoL consists of 27 Likert-scale items with factors (lifestyle, emotions, and work). Color vision was assessed using the Ishihara and Cambridge Mollen color vision tests. A six-point Likert scale was used, with lower scores indicating poor QoL (from 1 = severe issue to 6 = no problem)., Results: The CVD-QoL questionnaire's reliability and internal consistency were measured, including Cronbach's α (α =0.70-0.90). There was no significance between the group in age (t = -1.2, P = 0.67) whereas the Ishihara colour vision test, scores showed a significant difference (t = 4.50, P < 0.001). The QoL scores showed a significant difference towards lifestyle, emotions and work (P = 0.001). The CVD group had a poorer QoL score than the normal color vision group odds ratio [OR] =0.31, 95% confidence interval [CI], (P = 0.002, CI = 0.14-0.65, Z = 3.0) . In this analysis, a low CI indicated that the OR was more precise., Conclusion: Color vision deficiency affects Indians' QoL, according to this study. The mean scores of lifestyle, emotions, and work were lower than the UK sample.Since CVD is underreported and possibly affects developing countries more, advocacy for a new health care plan on CVD is essential. Increasing public understanding and awareness could also help diagnosing the CVD population., Competing Interests: None

Introduction: Computer vision and deep learning (DL) techniques have succeeded in a wide range of diverse fields. Recently, these techniques have been successfully deployed in plant science applications to address food security, productivity, and environmental sustainability problems for a growing global population. However, training these DL models often necessitates the large-scale manual annotation of data which frequently becomes a tedious and time-and-resource- intensive process. Recent advances in self-supervised learning (SSL) methods have proven instrumental in overcoming these obstacles, using purely unlabeled datasets to pre-train DL models., Methods: Here, we implement the popular self-supervised contrastive learning methods of NNCLR Nearest neighbor Contrastive Learning of visual Representations) and SimCLR (Simple framework for Contrastive Learning of visual Representations) for the classification of spatial orientation and segmentation of embryos of maize kernels. Maize kernels are imaged using a commercial high-throughput imaging system. This image data is often used in multiple downstream applications across both production and breeding applications, for instance, sorting for oil content based on segmenting and quantifying the scutellum's size and for classifying haploid and diploid kernels., Results and Discussion: We show that in both classification and segmentation problems, SSL techniques outperform their purely supervised transfer learning-based counterparts and are significantly more annotation efficient. Additionally, we show that a single SSL pre-trained model can be efficiently finetuned for both classification and segmentation, indicating good transferability across multiple downstream applications. Segmentation models with SSL-pretrained backbones produce DICE similarity coefficients of 0.81, higher than the 0.78 and 0.73 of those with ImageNet-pretrained and randomly initialized backbones, respectively. We observe that finetuning classification and segmentation models on as little as 1% annotation produces competitive results. These results show SSL provides a meaningful step forward in data efficiency with agricultural deep learning and computer vision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Nagasubramanian, Wang, Frei, Jubery, Lübberstedt and Ganapathysubramanian.)

Natural or synthetic graphite as precursors for the preparation of graphene oxide (GO) have constraints due to their limited availability, high reaction temperature for processing of synthetic graphite and higher generation cost. The use of oxidants, long reaction duration, the generation of toxic gases and residues of inorganic salts, the degree of hazard and low yield are some of the disadvantages of the oxidative-exfoliation methods. Under these circumstances, biomass waste usage as a precursor is a viable alternative. The conversion of biomass into GO by the pyrolysis method is ecofriendly with diverse applications, which partially overcomes the waste disposal problem encountered by the existing methods. In this study, graphene oxide (GO) is prepared from dry leaves of sugarcane plant through a two-step pyrolysis method using ferric (III) citrate as a catalyst, followed by treatment with conc. H 2 SO 4 . The synthesized GO is analyzed by UV-Vis., FTIR, XRD, SEM, TEM, EDS and Raman spectroscopy. The synthesized GO has many oxygen-containing functional groups (-OH, C-OH, COOH, C-O). It shows a sheet-like structure with a crystalline size of 10.08 nm. The GO has a graphitic structure due to the Raman shift of G (1339 cm -1 ) and D (1591 cm -1 ) bands. The prepared GO has multilayers due to the ratio of 0.92 between I D and I G . The weight ratios between carbon and oxygen are examined by SEM-EDS and TEM-EDS and found to be 3.35 and 38.11. This study reveals that the conversion of sugarcane dry leaves into the high-value-added material GO becomes realistic and feasible and thus reduces the production cost of GO.

Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of childhood. The molecular hallmark of JMML is hyperactivation of the Ras/MAPK pathway with the most common cause being mutations in the gene PTPN11, encoding the protein tyrosine phosphatase SHP2. Current strategies for treating JMML include using the hypomethylating agent, 5-azacitidine (5-Aza) or MEK inhibitors trametinib and PD0325901 (PD-901), but none of these are curative as monotherapy. Utilizing an Shp2 E76K/+ murine model of JMML, we show that the combination of 5-Aza and PD-901 modulates several hematologic abnormalities often seen in JMML patients, in part by reducing the burden of leukemic hematopoietic stem and progenitor cells (HSC/Ps). The reduced JMML features in drug-treated mice were associated with a decrease in p-MEK and p-ERK levels in Shp2 E76K/+ mice treated with the combination of 5-Aza and PD-901. RNA-sequencing analysis revealed a reduction in several RAS and MAPK signaling-related genes. Additionally, a decrease in the expression of genes associated with inflammation and myeloid leukemia was also observed in Shp2 E76K/+ mice treated with the combination of the two drugs. Finally, we report two patients with JMML and PTPN11 mutations treated with 5-Aza, trametinib, and chemotherapy who experienced a clinical response because of the combination treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Advances in imaging hardware allow high throughput capture of the detailed three-dimensional (3D) structure of plant canopies. The point cloud data is typically post-processed to extract coarse-scale geometric features (like volume, surface area, height, etc.) for downstream analysis. We extend feature extraction from 3D point cloud data to various additional features, which we denote as 'canopy fingerprints'. This is motivated by the successful application of the fingerprint concept for molecular fingerprints in chemistry applications and acoustic fingerprints in sound engineering applications. We developed an end-to-end pipeline to generate canopy fingerprints of a three-dimensional point cloud of soybean [ Glycine max (L.) Merr.] canopies grown in hill plots captured by a terrestrial laser scanner (TLS). The pipeline includes noise removal, registration, and plot extraction, followed by the canopy fingerprint generation. The canopy fingerprints are generated by splitting the data into multiple sub-canopy scale components and extracting sub-canopy scale geometric features. The generated canopy fingerprints are interpretable and can assist in identifying patterns in a database of canopies, querying similar canopies, or identifying canopies with a certain shape. The framework can be extended to other modalities (for instance, hyperspectral point clouds) and tuned to find the most informative fingerprint representation for downstream tasks. These canopy fingerprints can aid in the utilization of canopy traits at previously unutilized scales, and therefore have applications in plant breeding and resilient crop production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Young, Jubery, Carley, Carroll, Sarkar, Singh, Singh and Ganapathysubramanian.)

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca 2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca 2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Selenium (Se) is a microelement that plays an important nutrient role by influencing various physiological and biochemical traits in plants. It has been shown to stimulate plant metabolism, enhancing secondary metabolites and lowering abiotic and biotic stress in plants. Globally, the enormous applications of nanotechnology in the food and agricultural sectors have vastly expanded. Nanoselenium is more active than bulk materials, and various routes of synthesis of Se nanoparticles (Se-NPs) have been reported in which green synthesis using plants is more attractive due to a reduction in ecological issues and an increase in biological activities. The Se-NP-based biofortification is more significant because it increases plant stress tolerance and positively impacts their metabolism. Se-NPs can enhance plant resistance to various oxidative stresses, promote growth, enhance soil nutrient status, enhance plant antioxidant levels, and participate in the transpiration process. Additionally, they use a readily available, biodegradable reducing agent and are ecologically friendly. This review concentrates on notable information on the different modes of Se-NPs' synthesis and characterization, their applications in plant growth, yield, and stress tolerance, and their influence on the metabolic process.

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 Pantoea stewartii (H2) and Priestia aryabhattai (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 Pantoea stewartii and 3.6 nm for Priestia aryabhattai . 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 LC 50 and LC 90 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 Priestia aryabhattai -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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.