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This study aimed to optimize mesalamine (MES)-nanoparticles (NPs) using Box Behnken Design and investigate its in vivo antioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose (EC) NP containing MES has particles size of 142 ± 2.8 nm, zeta potential (ZP) of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed NPs has a uniform and spherical shape. The in-vitro release data disclosed that the EC NPs containing MES showed bursts release of 52% ± 1.6% in simulated stomach media within 2 h, followed by a steady release of 93% ± 2.9% in simulated intestinal fluid that lasted for 48 h. The MES release from NP best match with the Korsmeyer-Peppas model ( R = 0.962) and it followed Fickian diffusion case I release mechanism. The formulation stability over six-months at 25 °C ± 2 °C with 65% ± 5% relative humidity, and 40 °C ± 2 °C with 75% ± 5% relative humidity showed no significant changes in colour, EE, particle sizes and ZP. As per 2 results, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.in vivo results, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis., (Creative Commons Attribution license.)

Thuwalamides A-E (1, 3, 5, 6 and 8), previously undescribed polychlorinated amides, along with ten previously reported related compounds (2, 4, 7 and 9-15), were isolated from the organic extract of the marine sponge Lamellodysidea herbacea (Keller), collected off the village of Thuwal in the Red Sea at Saudi Arabia. The structures of the isolated compounds have been determined through extensive analysis of their NMR and MS data, while their absolute stereochemistry was unequivocally established via single crystal X-ray diffraction. Additionally, the absolute stereochemistry of the previously reported compounds 2 and 4, whose configuration was not determined, has also been established using single-crystal X-ray crystallographic analysis. The antibacterial activity of compounds 1-15 was evaluated against Escherichia coli and Staphylococcus aureus. Among them, compound 14 displayed activity against S. aureus comparable to vancomycin that was used as a positive control with a MIC value of 4 μg/mL., 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 © 2024 Elsevier Ltd. All rights reserved.)

This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.

14-3-3 proteins, ubiquitously present in eukaryotic cells, are regulatory proteins involved in a plethora of cellular processes. In plants, they have been studied in the context of metabolism, development, and stress responses. Recent studies have highlighted the pivotal role of 14-3-3 proteins in regulating plant immunity. The ability of 14-3-3 proteins to modulate immune responses is primarily attributed to their function as interaction hubs, mediating protein-protein interactions and thereby regulating the activity and overall function of their binding partners. Here, we shed light on how 14-3-3 proteins contribute to plant defense mechanisms, the implications of their interactions with components of plant immunity cascades, and the potential for leveraging this knowledge for crop improvement strategies., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024. Published by Elsevier Ltd.)

In the SARS-CoV-2 pandemic, the so far two most effective approved antivirals are the protease inhibitors nirmatrelvir, in combination with ritonavir (Paxlovid) and ensitrelvir (Xocova). However, antivirals and indeed all antimicrobial drugs are sooner or later challenged by resistance mutations. Studying such mutations is essential for treatment decisions and pandemic preparedness. At the same time, generating resistant viruses to assess mutants is controversial, especially with pathogens of pandemic potential like SARS-CoV-2. To circumvent gain-of-function research with non-attenuated SARS-CoV-2, a previously developed safe system based on a chimeric vesicular stomatitis virus dependent on the SARS-CoV-2 main protease (VSV-M pro ) was used to select mutations against ensitrelvir. Ensitrelvir is clinically especially relevant due to its single-substance formulation, avoiding drug-drug interactions by the co-formulated CYP3A4 inhibitor ritonavir in Paxlovid. By treating VSV-M pro with ensitrelvir, highly-specific resistant mutants against this inhibitor were selected, while being still fully or largely susceptible to nirmatrelvir. We then confirmed several ensitrelvir-specific mutants in gold standard enzymatic assays and SARS-CoV-2 replicons. These findings indicate that the two inhibitors can have distinct viral resistance profiles, which could determine treatment decisions., Competing Interests: Declaration of Competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. D.v.L. is founder of ViraTherapeutics GmbH. D.v.L serves as a scientific advisor to Boehringer Ingelheim and Pharma KG. E.H. and D.v.L have received an Austrian Science Fund (FWF) grant in the special call “SARS urgent funding”. J.P., X.H. and D.W. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. hold stocks of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. are inventors on the patent application “Coronavirus replicons for antiviral screening and testing”. All other authors declare no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS). Docking scores were further validated by multiple receptor conformer (MRC)-based docking studies. Based on the MRC-based docking results, eight molecules were shortlisted for ADMET analysis. Molecular dynamics (MD) simulations were further performed to evaluate the conformational stability of the ligand-protein complexes. Binding energies were computed by the gmx_MMPBSA method. The data were obtained in terms of root-mean square deviation, and root-mean square fluctuation justified the stability of Austrocortilutein A, Austrocortirubin, and Confluentin in complex with several proteins under physiological conditions. Among these, Austrocortilutein A displayed better binding affinity with PBP1a and ILERS when compared with their respective reference ligands. This study is preliminary and aims to help drive the search for compounds that have the capacity to overcome the anti-microbial resistance of prevalent bacteria, using natural compounds produced by wild mushrooms. Further experimental validation is required to justify the clinical use of the studied compounds., 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 Authors.)

Replication stress describes endogenous and exogenous challenges to DNA replication in the S-phase. Stress during this critical process causes helicase-polymerase decoupling at replication forks, triggering the S-phase checkpoint, which orchestrates global replication fork stalling and delayed entry into G2. The replication stressor most often used to induce the checkpoint response in yeast is hydroxyurea (HU), a clinically used chemotherapeutic. The primary mechanism of S-phase checkpoint activation by HU has thus far been considered to be a reduction of deoxynucleotide triphosphate synthesis by inhibition of ribonucleotide reductase (RNR), leading to helicase-polymerase decoupling and subsequent activation of the checkpoint, facilitated by the replisome-associated mediator Mrc1. In contrast, we observe that HU causes cell cycle arrest in budding yeast independent of both the Mrc1-mediated replication checkpoint response and the Psk1-Mrc1 oxidative signaling pathway. We demonstrate a direct relationship between HU incubation and reactive oxygen species (ROS) production in yeast and human cells and show that antioxidants restore growth of yeast in HU. We further observe that ROS strongly inhibits the in vitro polymerase activity of replicative polymerases (Pols), Pol α, Pol δ, and Pol ε, causing polymerase complex dissociation and subsequent loss of DNA substrate binding, likely through oxidation of their integral iron-sulfur (Fe-S) clusters. Finally, we present "RNR-deg," a genetically engineered alternative to HU in yeast with greatly increased specificity of RNR inhibition, allowing researchers to achieve fast, nontoxic, and more readily reversible checkpoint activation compared to HU, avoiding harmful ROS generation and associated downstream cellular effects that may confound interpretation of results., Competing Interests: Competing interests statement:The authors declare no competing interest.

Climate changes threat global food security and food production. Soil salinization is one of the major issues of changing climate, causing adverse impacts on agricultural crops. Germination and seedlings establishment are damaged under these conditions, so seeds must be safeguard before planting. Here, we use recycled organic tree waste combined with cold (low-pressure) plasma treatment as grain coating to improve the ability of wheat seed cultivars (Misr-1 and Gemmeza-11) to survive, germinate and produce healthy seedlings. The seeds were coated with biofilms of lignin and hash carbon to form a protective extracellular polymeric matrix and then exposed them to low-pressure plasma for different periods of time. The effectiveness of the coating and plasma was evaluated by characterizing the physical and surface properties of coated seeds using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) spectroscopy, and wettability testing. We also evaluated biological and physiological properties of coated seeds and plants they produced by studying germination and seedling vigor, as well as by characterizing fitness parameters of the plants derived from the seeds. The analysis revealed the optimal plasma exposure time to enhance germination and seedling growth. Taken together, our study suggests that combining the use of recycled organic tree waste and cold plasma may represent a viable strategy for improving crop seedlings performance, hence encouraging plants cultivation in stressed ecosystems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Elgendy 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 3D chromatin organization plays a major role in the control of gene expression. However, our comprehension of the governing principles behind nuclear organization remains incomplete. Particularly, the spatial segregation of loci with similar repressive transcriptional states in plants poses a significant yet poorly understood puzzle. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by β-amyloid (Aβ) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aβ and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aβ deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mpro resistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mpro variants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available protease inhibitors (nirmatrelvir and ensitrelvir) with cell-based, biochemical and SARS-CoV-2 replicon assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mpro inhibitors, will help to understand SARS-CoV-2 protease inhibitor resistance mechanisms and show the relevance of specific mutations, thereby informing treatment decisions., Competing Interests: D.v.L. is founder of ViraTherapeutics GmbH. D.v.L serves as a scientific advisor to Boehringer Ingelheim and Pharma KG. E.H. and D.v.L have received an Austrian Science Fund (FWF) grant in the special call “SARS urgent funding”. E.H. is a registered consultant at Guidepoint. S.A.M and R.S.H. are inventors on the patent application “Live cell assay for protease inhibition”, application number WO/2022/094463. J.P., X.H. and D.W. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. hold stocks of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. are inventors on the patent application “Coronavirus replicons for antiviral screening and testing”. This work is not in any way sponsored or to any extent influenced by any of the authors’ employment statuses. All other authors declare they have no competing interests., (Copyright: © 2024 Costacurta 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.)

Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes., Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis., Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis., Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 Alzahrani et al.)

Strigolactones exhibit dual functionality as regulators of plant architecture and signaling molecules in the rhizosphere. The important model crop rice exudes a blend of different strigolactones from its roots. Here, we identify the inaugural noncanonical strigolactone, 4-oxo-methyl carlactonoate (4-oxo-MeCLA), in rice root exudate. Comprehensive, cross-species coexpression analysis allowed us to identify a cytochrome P450, OsCYP706C2, and two methyl transferases as candidate enzymes for this noncanonical rice strigolactone biosynthetic pathway. Heterologous expression in yeast and Nicotiana benthamiana indeed demonstrated the role of these enzymes in the biosynthesis of 4-oxo-MeCLA, which, expectedly, is derived from carlactone as substrate. The oscyp706c2 mutants do not exhibit a tillering phenotype but do have delayed mycorrhizal colonization and altered root phenotype. This work sheds light onto the intricate complexity of strigolactone biosynthesis in rice and delineates its role in symbiosis and development.

Lipids play crucial roles in human biology, serving as energy stores, cell membranes, hormone production, and signaling molecules. Accordingly, their study under lipidomics has advanced the study of living organisms. 1-Dimensional (D) and 2D NMR methods, particularly 1D 1 H and 2D 1 H- 1 H Total Correlation Spectroscopy (TOCSY), are commonly used in lipidomics for quantification and structural identification. However, these NMR methods suffer from low sensitivity, especially in cases of low concentrated molecules such as protons attached to hydroxy, esters, aliphatic, or aromatic unsaturated carbons. Such molecules are common in complex mixtures such as dairy products and plant oils. On the other hand, lipids have highly populated fractions of methyl and methylene groups that result in intense peaks that overwhelm lower peaks and cause inhomogeneities in 2D TOCSY spectra. In this study, we applied a method of suppression to suppress these intense peaks of methyl and methylene groups to detect weaker peaks. The suppression method was investigated on samples of cheese, butter, a mixture of lipids, coconut oil, and olive oil. A significant improvement in peak sensitivity and visibility of cross-peaks was observed, leading to enhanced comparative quantification and structural identification of a greater number of lipids. Additionally, the enhanced sensitivity reduced the time required for the qualitative and comparative quantification of other lipid compounds and components. This, in turn, enables faster and more reliable structural identification and comparative quantification of a greater number of lipids. Additionally, it reduces the time required for the qualitative, and comparative quantification due to the enhancement of sensitivity., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (This journal is © The Royal Society of Chemistry.)

The simian virus 40 (SV40) replisome only encodes for its helicase; large T-antigen (L-Tag), while relying on the host for the remaining proteins, making it an intriguing model system. Despite being one of the earliest reconstituted eukaryotic systems, the interactions coordinating its activities and the identification of new factors remain largely unexplored. Herein, we in vitro reconstituted the SV40 replisome activities at the single-molecule level, including DNA unwinding by L-Tag and the single-stranded DNA-binding protein Replication Protein A (RPA), primer extension by DNA polymerase δ, and their concerted leading-strand synthesis. We show that RPA stimulates the processivity of L-Tag without altering its rate and that DNA polymerase δ forms a stable complex with L-Tag during leading-strand synthesis. Furthermore, similar to human and budding yeast Cdc45-MCM-GINS helicase, L-Tag uses the fork protection complex (FPC) and the mini-chromosome maintenance protein 10 (Mcm10) during synthesis. Hereby, we demonstrate that FPC increases this rate, and both FPC and Mcm10 increase the processivity by stabilizing stalled replisomes and increasing their chances of restarting synthesis. The detailed kinetics and novel factors of the SV40 replisome establish it as a closer mimic of the host replisome and expand its application as a model replication system., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.

The ocean's mercury (Hg) content has tripled due to anthropogenic activities, and although the dark ocean (>200 m) has become an important Hg reservoir, concentrations of the toxic and bioaccumulative methylmercury (MeHg) are low and therefore very difficult to measure. As a consequence, the current understanding of the Hg cycle in the deep ocean is severely data-limited, and the factors controlling MeHg, as well as its transformation rates, remain largely unknown. By analyzing 52 globally distributed bathypelagic deep-ocean metagenomes and 26 new metatranscriptomes from the Malaspina Expedition, our study reveals the widespread distribution and expression of bacterial-coding genes merA and merB in the global bathypelagic ocean (∼4000 m depth). These genes, associated with Hg II reduction and MeHg demethylation, respectively, are particularly prevalent within the particle-attached fraction. Moreover, our results indicate that water mass age and the organic matter composition shaped the structure of the communities harboring merA and merB genes living in different particle size fractions, their abundance, and their expression levels. Members of the orders Corynebacteriales , Rhodobacterales , Alteromonadales , Oceanospirillales , Moraxellales , and Flavobacteriales were the main taxonomic players containing merA and merB genes in the deep ocean. These findings, together with our previous results of pure culture isolates of the deep bathypelagic ocean possessing the metabolic capacity to degrade MeHg, indicated that both methylmercury demethylation and Hg II reduction likely occur in the global dark ocean, the largest biome in the biosphere.

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds., 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 © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Enantiopure 2-halo-1-arylethanols are essential precursors for the synthesis of pharmaceuticals, agrochemicals, and fine chemicals. This study investigates the asymmetric reduction of 2-haloacetophenones and their substituted analogs to obtain their corresponding optically active 2-halo-1-arylethanols using secondary alcohol dehydrogenase from Thermoanaerobacter pseudethanolicus ( Te SADH) mutants. Specifically, the ΔP84/A85G and P84S/A85G Te SADH mutants were evaluated for the asymmetric reduction of 2-haloacetophenones, generating their corresponding optically active halohydrins with high enantioselectivities. The asymmetric reduction of 2-haloacetophenones and their substituted analogs using the ΔP84/A85G Te SADH mutant yielded their corresponding ( S )-2-halo-1-arylethanols with high enantiopurity in accordance with the anti -Prelog's rule. Conversely, the P84S/A85G Te SADH mutant produced ( R )-alcohols when reducing 2-chloro-4'-chloroacetophenone, 2-chloro-4'-bromoacetophenone, and 2-bromo-4'-chloroacetophenone, while generating the ( S )-configured halohydrin from 2-chloro-4'-fluoroacetophenone. Asymmetric reduction of the unsubstituted 2-bromoacetophenone, 2-chloroacetophenone, and 2,2,2-trifluoroacetophenone resulted in production of their ( S )-halohydrins with the tested mutants, which reflects the importance of the nature of the substituent on the substrate's ring in controlling the stereopreference of these Te SADH-catalyzed reduction reactions. These findings contribute to the understanding and application of Te SADH in synthesizing optically active compounds and aid in the design of further mutants with the desired stereopreference., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs., 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 Alghrably, Bennici, Szczupaj, Alasmael, Qutub, Maatouk, Chandra, Nowakowski, Emwas and Jaremko.)

Root-knot nematodes (RKNs) are a vital pest that causes significant yield losses and economic damage to potato plants. The use of chemical pesticides to control these nematodes has led to environmental concerns and the development of resistance in the nematode populations. Endophytic fungi offer an eco-friendly alternative to control these pests and produce secondary metabolites that have nematicidal activity against RKNs. The objective of this study is to assess the efficacy of Aspergillus flavus (ON146363), an entophyte fungus isolated from Trigonella foenum-graecum seeds, against Meloidogyne incognita in filtered culture broth using GC-MS analysis. Among them, various nematicidal secondary metabolites were produced: Gadoleic acid, Oleic acid di-ethanolamide, Oleic acid, and Palmitic acid. In addition, biochemical compounds such as Gallic acid, Catechin, Protocatechuic acid, Esculatin, Vanillic acid, Pyrocatechol, Coumarine, Cinnamic acid, 4, 3-indol butyl acetic acid and Naphthyl acetic acid by HPLC. The fungus was identified through morphological and molecular analysis, including ITS 1-4 regions of ribosomal DNA. In vitro experiments showed that culture filtrate of A. flavus had a variable effect on reducing the number of egg hatchings and larval mortality, with higher concentrations showing greater efficacy than Abamectin. The fungus inhibited the development and multiplication of M. incognita in potato plants, reducing the number of galls and eggs by 90% and 89%, respectively. A. flavus increased the activity of defense-related enzymes Chitinas, Catalyse, and Peroxidase after 15, 45, and 60 days. Leaching of the concentrated culture significantly reduced the second juveniles' stage to 97% /250 g soil and decreased the penetration of nematodes into the roots. A. flavus cultural filtrates via soil spraying improved seedling growth and reduced nematode propagation, resulting in systemic resistance to nematode infection. Therefore, A. flavus can be an effective biological control agent for root-knot nematodes in potato plants. This approach provides a sustainable solution for farmers and minimizes the environmental impact., (© 2024. The Author(s).)

A cell's ability to survive and to evade cancer is contingent on its ability to retain genomic integrity, which can be seriously compromised when nucleic acid phosphodiester bonds are disrupted. DNA Ligase 1 (LIG1) plays a key role in genome maintenance by sealing single-stranded nicks that are produced during DNA replication and repair. Autosomal recessive mutations in a limited number of individuals have been previously described for this gene. Here we report a homozygous LIG1 mutation (p.A624T), affecting a universally conserved residue, in a patient presenting with leukopenia, neutropenia, lymphopenia, pan-hypogammaglobulinemia, and diminished in vitro response to mitogen stimulation. Patient fibroblasts expressed normal levels of LIG1 protein but exhibited impaired growth, poor viability, high baseline levels of gamma-H2AX foci, and an enhanced susceptibility to DNA-damaging agents. The mutation reduced LIG1 activity by lowering its affinity for magnesium 2.5-fold. Remarkably, it also increased LIG1 fidelity > 50-fold against 3' end 8-Oxoguanine mismatches, exhibiting a marked reduction in its ability to process such nicks. This is expected to yield increased ss- and dsDNA breaks. Molecular dynamic simulations, and Residue Interaction Network studies, predicted an allosteric effect for this mutation on the protein loops associated with the LIG1 high-fidelity magnesium, as well as on DNA binding within the adenylation domain. These dual alterations of suppressed activity and enhanced fidelity, arising from a single mutation, underscore the mechanistic picture of how a LIG1 defect can lead to severe immunological disease., (© 2024. The Author(s).)

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Omran, Alzahrani, Ezzat, Ellithy, Tarek, Khairy, Ghit, Elgeushy, Ibrahim Al-Hazani, Aziz Ibrahim, Falemban, Bamagous, Elhawary, Jaremko, Saied and Mohamed.)

Sodium nitrite (NaNO 2 ) is a widely used food ingredient, although excessive concentrations can pose potential health risks. In the present study, we evaluated the deterioration effects of NaNO 2 additives on hematology, metabolic profile, liver function, and kidney function of male Wistar rats. We further explored the therapeutic potential of supplementation with S. costus root ethanolic extract (SCREE) to improve NaNO 2 -induced hepatorenal toxicity. In this regard, 65 adult male rats were divided into eight groups; Group 1: control, Groups 2, 3, and 4 received SCREE in 200, 400, and 600 mg/kg body weight, respectively, Group 5: NaNO 2 (6.5 mg/kg body weight), Groups 6, 7 and 8 received NaNO 2 (6.5 mg/kg body weight) in combination with SCREE (200, 400, and 600 mg/kg body weight), respectively. Our results revealed that the NaNO 2 -treated group shows a significant change in deterioration in body and organ weights, hematological parameters, lipid profile, and hepatorenal dysfunction, as well as immunohistochemical and histopathological alterations. Furthermore, the NaNO 2 -treated group demonstrated a considerable increase in the expression of TNF-α cytokine and tumor suppressor gene P53 in the kidney and liver, while a significant reduction was detected in the anti-inflammatory cytokine IL-4 and the apoptosis suppressor gene BCL-2, compared to the control group. Interestingly, SCREE administration demonstrated the ability to significantly alleviate the toxic effects of NaNO 2 and improve liver function in a dose-dependent manner, including hematological parameters, lipid profile, and modulation of histopathological architecture. Additionally, SCREE exhibited the ability to modulate the expression levels of inflammatory cytokines and apoptotic genes in the liver and kidney. The phytochemical analysis revealed a wide set of primary metabolites in SCREE, including phenolics, flavonoids, vitamins, alkaloids, saponins and tannins, while the untargeted UPLC/T-TOF-MS/MS analysis identified 183 metabolites in both positive and negative ionization modes. Together, our findings establish the potential of SCREE in mitigating the toxic effects of NaNO 2 by modulating metabolic, inflammatory, and apoptosis. Together, this study underscores the promise of SCREE as a potential natural food detoxifying additive to counteract the harmful impacts of sodium nitrite., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Elshaer, Hamad, Sobhy, Darwish, Baghdadi, H. Abo Nahas, El-Demerdash, Kabeil, Altamimi, Al-Olayan, Alsunbul, Docmac, Jaremko, Hafez and Saied.)

Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates. The majority of cases of diabetes in 2021 (>90.0%) were type 2 diabetes, which is largely indicative of the prevalence of diabetes in general, particularly in older adults (K. L. Ong, et al. , Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021, Lancet , 2023, 402 (10397), 203-234). Nowadays, slowing the progression of diabetic complications is the only effective way to manage diabetes with the available therapeutic options. However, novel biomarkers and treatments are urgently needed to control cytokine secretion, advanced glycation end products (AGEs) production, vascular inflammatory effects, and cellular death. Emerging research has highlighted the intricate interplay between reactive oxygen species (ROS) and protein aggregation in the pathogenesis of diabetes. In this scenario, the main aim of this paper is to provide a comprehensive review of the current understanding of the molecular mechanisms underlying ROS-induced cellular damage and protein aggregation, specifically focusing on their contribution to diabetes development. The role of ROS as key mediators of oxidative stress in diabetes is discussed, emphasizing their impact on cellular components and signaling. Additionally, the involvement of protein aggregation in impairing cellular function and insulin signaling is explored. The synergistic effects of ROS and protein aggregation in promoting β-cell dysfunction and insulin resistance are examined, shedding light on potential targets for therapeutic intervention., Competing Interests: All authors declare that they have no conflicts of interest that could inappropriately influence this manuscript., (This journal is © The Royal Society of Chemistry.)

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Microbial biofilms are behind microbiologically influenced corrosion (MIC). Sessile cells in biofilms are many times more concentrated volumetrically than planktonic cells in the bulk fluids, thus providing locally high concentrations of chemicals. More importantly, "electroactive" sessile cells in biofilms are capable of utilizing extracellularly supplied electrons (e.g., from elemental Fe) for intracellular reduction of an oxidant such as sulfate in energy metabolism. MIC directly caused by anaerobic biofilms is classified into two main types based on their mechanisms: extracellular electron transfer MIC (EET-MIC) and metabolite MIC (M-MIC). Sulfate-reducing bacteria (SRB) are notorious for their corrosivity. They can cause EET-MIC in carbon steel, but they can also secrete biogenic H 2 S to corrode other metals such as Cu directly via M-MIC. This study investigated the use of conductive magnetic nanowires as electron mediators to accelerate and thus identify EET-MIC of C1020 by Desulfovibrio vulgaris. The presence of 40 ppm (w/w) nanowires in ATCC 1249 culture medium at 37 °C resulted in 45 % higher weight loss and 57 % deeper corrosion pits after 7-day incubation. Electrochemical tests using linear polarization resistance and potentiodynamic polarization supported the weight loss data trend. These findings suggest that conductive magnetic nanowires can be employed to identify EET-MIC. The use of insoluble 2 μm long nanowires proved that the extracellular section of the electron transfer process is a bottleneck in SRB MIC of carbon steel., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The secretory pathway is essential for plant immunity, delivering diverse antimicrobial molecules into the extracellular space. Arabidopsis thaliana soluble N-ethylmaleimide-sensitive-factor attachment protein receptor SNAP33 is a key actor of this process. The snap33 mutant displays dwarfism and necrotic lesions, however the molecular determinants of its macroscopic phenotypes remain elusive. Here, we isolated several new snap33 mutants that exhibited constitutive cell death and H 2 O 2 accumulation, further defining snap33 as an autoimmune mutant. We then carried out quantitative transcriptomic and proteomic analyses showing that numerous defense transcripts and proteins were up-regulated in the snap33 mutant, among which genes/proteins involved in defense hormone, pattern-triggered immunity, and nucleotide-binding domain leucine-rich-repeat receptor signaling. qRT-PCR analyses and hormone dosages supported these results. Furthermore, genetic analyses elucidated the diverse contributions of the main defense hormones and some nucleotide-binding domain leucine-rich-repeat receptor signaling actors in the establishment of the snap33 phenotype, emphasizing the preponderant role of salicylic acid over other defense phytohormones. Moreover, the accumulation of pattern-triggered immunity and nucleotide-binding domain leucine-rich-repeat receptor signaling proteins in the snap33 mutant was confirmed by immunoblotting analyses and further shown to be salicylic acid-dependent. Collectively, this study unveiled molecular determinants underlying the Arabidopsis snap33 mutant phenotype and brought new insights into autoimmunity signaling., (© 2024 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Key Message: Modification of silent latent endosperm-enabled promoters (SLEEPERs) allows the ectopic activation of non-expressed metabolic genes in rice callus Metabolic engineering in plants typically involves transgene expression or the mutation of endogenous genes. An alternative is promoter modification, where small changes in the promoter sequence allow genes to be switched on or off in particular tissues. To activate silent genes in rice endosperm, we screened native promoters for near-miss cis-acting elements that can be converted to endosperm-active regulatory motifs. We chose rice PHYTOENE SYNTHASE 1 (PSY1), encoding the enzyme responsible for the first committed step in the carotenoid biosynthesis pathway, because it is not expressed in rice endosperm. We identified six motifs within a 120-bp region, upstream of the transcriptional start site, which differed from endosperm-active elements by up to four nucleotides. We mutated four motifs to match functional elements in the endosperm-active BCH2 promoter, and this promoter was able to drive GFP expression in callus and in seeds of regenerated plants. The 4 M promoter was not sufficient to drive PSY1 expression, so we mutated the remaining two elements and used the resulting 6 M promoter to drive PSY1 expression in combination with a PDS transgene. This resulted in deep orange callus tissue indicating the accumulation of carotenoids, which was subsequently confirmed by targeted metabolomics analysis. PSY1 expression driven by the uncorrected or 4 M variants of the promoter plus a PDS transgene produced callus that lacked carotenoids. These results confirm that the adjustment of promoter elements can facilitate the ectopic activation of endogenous plant promoters in rice callus and endosperm and most likely in other tissues and plant species., (© 2024. The Author(s).)

Senescence is an important physiological process which directly affects many agronomic traits in plants. Senescence induces chlorophyll degradation, phytohormone changes, cellular structure damage, and altered gene regulation. Although these physiological outputs are well defined, the molecular mechanisms employed are not known. Using dark-induced leaf senescence (DILS) as the experimental system, we investigated the role of N6-methyladenosine (m6A) mRNA methylation during senescence in Arabidopsis (Arabidopsis thaliana). Plants compromised in m6A machinery components like METHYLTRANSFERASE A (mta mutant) and VIRILIZER1 (vir-1 mutant) showed an enhanced DILS phenotype. This was accompanied by compromised chloroplast and photosynthesis performance in mta as well as accumulation of senescence-promoting camalexin and phytohormone jasmonic acid after dark treatment. m6A levels increased during DILS and destabilized senescence-related transcripts thereby preventing premature aging. Due to inefficient decay, senescence-related transcripts like ORESARA1 (ORE1), SENESCENCE-ASSOCIATED GENE 21 (SAG21), NAC-like, activated by AP3/PI (NAP), and NONYELLOWING 1 (NYE1) over-accumulated in mta thereby causing accelerated senescence during DILS. Overall, our data propose that m6A modification is involved in regulating the biological response to senescence in plants, providing targets for engineering stress tolerance of crops., Competing Interests: Conflict of interest statement. The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta-meta, meta-para, para-meta, and para-para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV β-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor., (© 2024. The Author(s).)

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Mangrove forests are recognized as one of the most effective ecosystems for storing carbon. In drylands, mangroves operate at the extremes of environmental gradients and, in many instances, offer one of the few opportunities for vegetation-based sequestering of carbon. Developing accurate and reproducible methods to map carbon assimilation in mangroves not only serves to inform efforts related to natural capital accounting, but can help to motivate their protection and preservation. Remote sensing offers a means to retrieve numerous vegetation traits, many of which can be related to plant biophysical or biochemical responses. The leaf area index (LAI) is routinely employed as a biophysical indicator of health and condition. Here, we apply a linear regression model to UAV-derived multispectral data to retrieve LAI across three mangrove sites located along the coastline of the Red Sea, with estimates producing an R 2 of 0.72 when compared against ground-sampled LiCOR LAI-2200C LAI data. To explore the potential of monitoring carbon assimilation within these mangrove stands, the UAV-derived LAI estimates were combined with field-measured net photosynthesis rates from a LiCOR 6400/XT, providing a first estimate of carbon assimilation in dryland mangrove systems of approximately 3000 ton C km -2  yr -1 . Overall, these results advance our understanding of carbon assimilation in dryland mangroves and provide a mechanism to quantify the carbon mitigation potential of mangrove reforestation efforts., (© 2024. The Author(s).)