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In this study, Bacillus tequilensis TB5 α-amylase from rice-milled by-products (rice bran and de-oiled rice bran) was successfully immobilized onto biologically synthesized magnetic nanoparticles fabricated with chitosan (MNP-Ch) and characterized via different biophysical techniques. Furthermore, the study emphasized incorporating this nanostructure framework (MNP@2mgchitosan_DORB-amy and MNP@3mgchitosan_RB-amy) to offer diverse applications, including enzymatic desizing, cleaning starchy stains, and treating synthetic starchy wastewater. An enzyme loading of > 90 % for both enzymes indicated increased binding sites due to the functional moieties of chitosan on the MNP. The K m was 0.28 and 0.31 mg/mL for the immobilized and free forms of DORB-amy, respectively, and 0.18 and 0.27 mg/mL for the immobilized and free forms of RB-amy, respectively. A low K m indicated an increased affinity of MNP-Ch-immobilized forms of enzymes toward the substrate. The performance of both immobilized enzymes improved at a wide range of pH and temperature, which may be attributed to the covalent binding of the enzyme on to the MNP-Ch. The nanobiocatalysts in the detergent act synergistically to fade the starchy stains. Furthermore, an 8-9 TEGEWA scale rating with > 11 % of starch removal was obtained through the biodesizing of starch-sized cotton fabric. The nanobiocatalyst efficiently decomposed starch and liberated 650-670 mg/L of reducing sugar from the synthetic wastewater, therefore offering promising opportunities for its exploration in a wastewater treatment plant. Thus, the study recommends the potential exploration of sturdy matrices like MNP to offer remarkable applications with maximum operational stability, easier recovery, and higher efficiency., 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 Inc. All rights reserved.)

Global public health is confronted with significant challenges due to the prevalence of cancer and the emergence of treatment resistance. This work focuses on the identification of cyclin-dependent kinase 2 (CDK2) through a systematic computational approach to discover novel cancer therapeutics. A ligand-based pharmacophore model was initially developed using a training set of seven potent CDK2 inhibitors. The obtained most robust model was characterized by three features: one donor (|Don|) and two acceptors (|Acc|). Screening this model against the ZINC database resulted in identifying 108 hits, which underwent further molecular docking studies. The docking results indicated binding affinity, with energy values ranging from -6.59 kcal mol⁻¹ to -7.40 kcal mol⁻¹ compared to the standard Roscovitine. The top 10 compounds (Z1-Z10) selected from the docking data were further screened for ADMET profiling, ensuring their compliance with pharmacokinetic and toxicological criteria. The top 3 compounds (Z1-Z3) chosen from the docking were subjected to Density Functional Theory (DFT) studies. They revealed significant variations in electronic properties, providing insights into the reactivity, stability, and polarity of these compounds. Molecular dynamics simulations confirmed the stability of the ligand-protein complexes, with acceptable RMSD and RMSF values. Specifically, compound Z1 demonstrated stability, around 2.4 Å, and maintained throughout the 100 ns simulation period with minimal conformational changes, stable RMSD, and consistent protein-ligand interactions., 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.)

In the modern environment conscious era, there has been a huge demand for the effective green method to fabricate biomaterials for sustained transdermal release of diltiazem hydrochloride to treat hypertension and cardiac failure. In this vein, the present study explores the amination of waste jute sourced nanocellulose (ANC) and its effect as a reinforcing filler to design electrospun polyvinyl alcohol (PVA)/chitosan based polymeric nanofibrous scaffold for drug delivery. The characterization results of FTIR (Fourier Transform Infrared Spectroscopy) confirm the successful chemical modification of nanocellulose (NCC). SEM (Scanning Electron Microscopy) results indicate the morphological modifications in ANC due to grafting. ANC enhances the mechanical properties of scaffold and sustains the release of the loaded drug to 67.89±3.39% as compared to the pure PVA/chitosan scaffold of 92.63±4.63% over a period of 72 h as shown by the results of in-vitro drug release study. Moreover, the incorporation of 0.5 % ANC improves the anti-bacterial activity against both gram-positive (97.4±4.87%, reduction in viable cells count) and gram-negative bacteria (98.5±4.93%, reduction in viable cells count). Further, the skin irritation and MTT assay authenticate the biocompatibility of the developed scaffold. The overall findings hence prove the efficacy of the engineered scaffold as a potential transdermal patch for sustained drug delivery applications., 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 B.V. All rights reserved.)

Background: The effect of thrombocytopenia has not been studied in the era of novel treatments in multiple myeloma (MM)., Objective: To evaluate the clinical characteristics and outcomes in MM patients presenting with thrombocytopenia., Materials: Newly diagnosed MM patients between 2008 and 2018 who received at least 2 novel agents at induction. Thrombocytopenia was defined as a platelet count of less than < 150,000/mm 3 ., Results: A total of 648 patients were identified. Thrombocytopenia was found in 120 patients (18.5%). Baseline disease characteristics associated with higher rates of thrombocytopenia at baseline included IgA myeloma, P < .01, ISS 3 versus 1 or 2, P < .01, R-ISS 3 versus 1 or 2, P < .01, renal failure (CrCl < 30 mL/min), P < .01, hypercalcemia (Ca > 11.5 mg/dL), P < .01, elevated LDH, P < .03, anemia (Hb < 10 g/dL), P < .01, higher serum monoclonal protein, P < .02, and > 60% plasma cells in the bone marrow, P < .01. Thrombocytopenia was more prevalent across patients with t(4;14) and t(14;16), but was not associated with an overall high-risk fluorescence in situ hybridization (FISH) classification. Median OS was significantly lower among patients with thrombocytopenia (64.4 vs. 145.0 months, P < .01). In multivariable Cox regression, thrombocytopenia was associated with mortality (HR = 2.45, 95% CI, 1.7-3.6) independently of age, sex, high-risk FISH, ISS stage, response at induction, percentage of plasma cells in the BM, and anemia., Conclusion: We found that thrombocytopenia was seen among one-fifth of MM patients and was more common in patients with (t[4; 14] and t[14; 16]). Thrombocytopenia had an independent association with worse survival., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract. The present study attempted to understand the codon usage preferences in genes associated with IBD progression. Compositional analysis, codon usage bias (CUB), Relative synonymous codon usage (RSCU), RNA structure, and expression analysis were performed to obtain a comprehensive picture of codon usage in IBD genes. Compositional analysis of 62 IBD-associated genes revealed that G and T are the most and least abundant nucleotides, respectively. ApG, CpA, and TpG dinucleotides were overrepresented or randomly used, while ApC, CpG, GpT, and TpA dinucleotides were either underrepresented or randomly used in genes related to IBD. The codons influencing the codon usage the most in IBD genes were CGC and AGG. A comparison of codon usage between IBD, and pancreatitis (non-IBD inflammatory disease) indicated that only codon CTG codon usage was significantly different between IBD and pancreatitis. At the same time, there were codons ATA, ACA, CGT, CAA, GTA, CCT, ATT, GCT, CGG, TTG, and CAG for whom codon usage was significantly different for IBD and housekeeping gene sets. The results suggest similar codon usage in at least two inflammatory disorders, IBD and pancreatitis. The analysis helps understand the codon biology, factors affecting gene expression of IBD-associated genes, and the evolution of these genes. The study helps reveal the molecular patterns associated with IBD., 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 B.V. All rights reserved.)

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity., 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. Published by Elsevier B.V.)

Biodegradable and sustainable food preservation materials have gained immense global importance to mitigate plastic pollution and environmental impact. Biopolymers like cellulose offer significant advantages for food preservation, including biodegradability and the ability to extend shelf life. Therefore, the present study aims to prepare gallic acid (GA) and zinc oxide nanoparticles (ZnO NPs) incorporated methylcellulose (MC) composite films by employing a solvent casting technique. The homogeneous SEM micrographs and FTIR spectra evidenced high compatibility among MC and GA/ZnO NPs. The UV barrier capacity, mechanical properties and surface hydrophobicity are remarkably enhanced by GA/ZnO NPs. However, the water vapour permeability and oxygen permeability of MGZ films were reduced by 49.19 % and 57.75 % respectively. Moreover, the MGZ films demonstrated exceptional antioxidant efficacy (∼94.48 %) and inhibition against food-borne pathogens such as B. subtilis, S. aureus (Gram-positive), E. coli, P. aeruginosa (Gram-negative), and C. albicans fungi. Furthermore, the GA/ZnO NPs extended the shelf life of MGZ coated tomato samples up to 27 days and exhibited controlled microbial growth after the preservation study. These results support the application of MGZ films as suitable and effective coating materials for food packaging applications., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Designing stimuli-responsive drug delivery vehicles with higher drug loading capacity, sustained and targeted release of anti-cancer drugs and able to mitigate the shortcomings of traditional systems is need of hour. Herein, we designed stimuli-responsive, self-healable, and adhesive hydrogel through synergetic interaction between [Cho][Gly] (Choline-Glycine) and sodium alginate (SA). The hydrogel was formed as a result of non-covalent interaction between the components of the mixture forming the fibre kind morphology; confirmed through FTIR/computational analysis and SEM/AFM images. The hydrogel exhibited excellent mechanical strength, self-healing ability, adhesive character and most importantly; adjustable injectability. In vitro biocompatibility of the hydrogel was tested on HaCaT and MCF-7 cells, showing >92 % cell viability after 48 h. The hemolysis ratio (<4 %) of the hydrogel confirmed the blood compatibility of the hydrogel. When tested for drug-loading capacity, the hydrogel show 1500 times drug loading for the 5-fluorouracil (5-FU) against the SA based hydrogel. In vitro release data indicated that 5-FU have more preference towards the cancerous cell condition, i.e. acidic pH (>85 %), whereas the drug-loaded hydrogel successfully killed the MCF-7 and HeLa cell with a 50 -1.92 mM value. The studied hydrogel paves way towards controlled and sustained delivery of anti-cancer drug for the treatment of breast cancer., 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 B.V. All rights reserved.)

This study provides the first documentation of three deep conspecific lineages within Panulirus polyphagus in the Indian Ocean, bridging the gap in genetic research. Comparative mitogenomics between lineages (L) at both species and family levels, evolutionary relationships and heterogeneity of sequence divergence within Decapoda, and divergence time estimation were performed. The characterized mitogenomes ranged from 15,685-15,705 bp in size and exhibited a typical pancrustacean pattern. Among the three lineages, L1 predominated the Bay of Bengal, L2 the Arabian Sea, and L2.a, a less common lineage genetically closer to L2, was restricted to the latter region. A minor lineage L1.a, was observed in the Coral Triangle area. All PCGs displayed evidence of purifying selection across species and family levels. The largest genetic distance (K2P) between lineages was 9 %, notably between L1.a and L2.a. The phylogenetic tree subdivided the Achelates into Palinuridae and Scyllaridae, and the topology demonstrated a distinct pattern of lineage diversification within P. polyphagus. AliGROOVE analysis revealed no discernible divergence in Decapoda. The diversification of P. polyphagus appears to have occurred during Miocene, with further diversification in Pliocene. Furthermore, genetic stocks and population connectivity recognized here will provide valuable insight for spatial management planning of this dwindling resource., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coastal pollutants, from harmful algal blooms, sewage and industrial discharges, pose severe risks to marine ecosystems and public health. Recently, Promenade Beach in Puducherry, Southeast-India, experienced reddish-brown water discoloration, suspected to result from either algal blooms or suspended matter. This study monitored the spatial extent and characteristics of the discoloration using Sentinel-2 satellite images from September to November 2023, with field observations and laboratory analyses. Analyses included measurements of chlorophyll-a (Chl-a), Total Suspended Matter (TSM), and the Normalized Difference Chlorophyll Index (NDCI) to differentiate between algal blooms and other pollutants. The satellite data indicated extents of discoloration, with high TSM concentrations (>45 g/m 3 ) and negative NDCI values suggesting absence of algal blooms. No mortality of aquatic organisms was observed during this discoloration, indicating no deleterious impact on aquatic life. This approach highlights the importance of combining satellite technology with field data for effective coastal pollution monitoring, essential for protecting marine ecosystems., 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. We wish to confirm that there are no known conflicts of interest associated with this publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The use of phytomedicine in cancer therapy is a growing field of research that takes use of the medicinal properties of plant-derived compounds. Under the domain of cancer therapy and management, alkaloids, a prominent group of natural compounds, show significant potential. Alkaloids often affect a wide range of essential cellular mechanisms involved in cancer progression. Using this multi-target method may give significant advantages to alkaloids in overcoming resistance mechanisms. For example, berberine, an alkaloid found in Berberis species, may induce apoptosis by activating caspases and regulating apoptotic pathways. Notably, alkaloids like as quinine have showed promise in inhibiting the formation of new blood vessels required for tumor growth. In addition, alkaloids have shown anti-proliferative and anticancer properties mostly via modulating key signaling pathways involved in metastasis, including those regulating epithelial-mesenchymal transition. This work provides a comprehensive overview of naturally occurring alkaloids that exhibit anticancer properties, with a specific emphasis on their underlying molecular mechanisms of action. Furthermore, many methods to modify previously reported difficult physicochemical properties using nanocarriers in order to enhance its systemic bioavailability have been discussed. This study also includes information on newly discovered alkaloids that are now being studied in clinical trials for their potential use in cancer treatment. Further, we have also briefly mentioned on the application of high-throughput screening and molecular dynamics simulation for acceleration on the identification of potent alkaloids based compounds to target and treat cancer., (Copyright © 2024. Published by Elsevier B.V.)

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM) despite common toxicities including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 milligrams (mg) once weekly was associated with lower mortality than higher doses of dexamethasone. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM have not been fully characterized. We conducted a secondary pooled analysis of the S0777 and S1211 SWOG studies of NDMM, which employed lenalidomide-dexamethasone (Rd) alone with or without bortezomib (VRd) and with or without elotuzumab (Elo-VRd). Planned dexamethasone intensity was 40-60 mg weekly in all arms. Patients were categorized into FD-DEX (full-dose dexamethasone maintained throughout induction) or LD-DEX (lowered-dose dexamethasone or discontinuation; only permitted for Grade 3+ toxicities per both study protocols). Of 541 evaluated patients, the LD-DEX group comprised 373 patients (69%). There was no difference in PFS or OS between the FD-DEX or LD-DEX groups, which were balanced in terms of age, stage, and performance status. Predictors of PFS and OS in multivariate models were treatment arm, age ≥70, and thrombocytopenia; FD-DEX did not significantly improve either outcome. Our study suggests that dexamethasone dose reductions are common in multiple myeloma, even within clinical trials. Given dexamethasone's many toxicities and unclear benefit in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective study. NCT00644228, NCT01668719., (Copyright © 2024 American Society of Hematology.)

The current study is intended to enhance unique bioactive and eco-friendly composite films following a simple solvent-casting approach by incorporating cerium oxide nanoparticles (CeO 2 NPs) with a chitosan (CS)/polyvinyl alcohol (PVA) matrix. Antimicrobial activity, preservation impact, mechanisms for the edible berry tomatoes and physicochemical properties of the produced films were tested. FTIR, SEM-EDX, XRD, UV-vis spectroscopy and contact angle were used to characterize the films. Incorporated (3.0 wt%) CeO 2 NPs practically developed composite film's thermal stability, structural, mechanical, bioactive, antioxidant, barrier and wettability properties. The tomatoes' look, weight loss and stiffness were better preserved after 25 days of storage at room temperature (25 ± 5 °C) when 3.0 wt% CeO 2 NPs films were used instead of the original CS/PVA film. CS and CeO 2 NPs have unique physiochemical and antibacterial properties. Food packaging extensively investigates the modified films as antimicrobials and preservatives to increase the shelf life of packaged foods, owing to their ability to inhibit gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa), and filamentous fungi (Bipolaris sorokiniana, Fusarium op., and Alternaria sp.). Our findings indicated that the CeO 2 /CS/PVA composite films could be used as effective wrapping materials for food preservation., Competing Interests: Declaration of competing interest No conflict of interest has been reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cell-fusion mediated generation of multinucleated syncytia represent critical feature during viral infection and in development. Efficiency of syncytia formation is usually illustrated as fusion efficiency under given condition by quantifying total number of nuclei in syncytia normalized to total number of nuclei (both within syncytia and unfused cell nuclei) in unit field of view. However heterogeneity in multinucleated syncytia sizes poses challenge in quantification of cell-fusion multinucleation under diverse conditions. Taking in-vitro SARS-CoV-2 spike-protein variants mediated virus-cell fusion model and placenta trophoblast syncytialization as cell-cell fusion model; herein we emphasize wide application of simple unbiased detailed measure of virus-cell and cell-cell multinucleation using experiential cumulative distribution function (CDF) and fusion number events (FNE) approaches illustrating comprehensive metrics for syncytia interpretation., 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 Inc. All rights reserved.)

Matrix Metalloproteinases (MMPs), which are endopeptidase reliant on zinc, are low in embryonic tissues but increases in response to a variety of physiological stimulus and pathological stresses. Neuro-glial cells, endothelial cells, fibroblasts, and leucocytes secrete MMPs, which cleave extracellular matrix proteins in a time-dependent manner. MMPs affect synaptic plasticity and the development of short-term memory by controlling the size, shape, and excitatory synapses' function through the lateral diffusion of receptors. In addition, MMPs influence the Extracellular Matrix proteins in the Peri-Neuronal Net at the Neuro-glial interface, which aids in the establishment of long-term memory. Through modulating neuronal, and glial cells migration, differentiation, Neurogenesis, and survival, MMPs impact brain development in mammals. In adult brains, MMPs play a beneficial role in physiological plasticity, which includes learning, memory consolidation, social interaction, and complex behaviors, by proteolytically altering a wide variety of factors, including growth factors, cytokines, receptors, DNA repair enzymes, and matrix proteins. Additionally, stress, depression, addiction, hepatic encephalopathy, and stroke may all have negative effects on MMPs. In addition to their role in glioblastoma development, MMPs influence neurological diseases such as epilepsy, schizophrenia, autism spectrum disorder, brain damage, pain, neurodegeneration, and Alzheimer's and Parkinson's. To help shed light on the potential of MMPs as a therapeutic target for neurodegenerative diseases, this review summarizes their regulation, mode of action, and participation in brain physiological plasticity and pathological damage. Finally, by employing different MMP-based nanotools and inhibitors, MMPs may also be utilized to map the anatomical and functional connectome of the brain, analyze its secretome, and treat neurodegenerative illnesses., Competing Interests: Declaration of competing interest The authors declare no conflicting interests., (Copyright © 2024. Published by Elsevier B.V.)

In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds 2, 4 and 5 inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of 1, 2, 3, 4 and 5 against the protein 1F9F were -8.01, -8.70, -9.43, -9.58 and -9.75 kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (1). ADMET analyses of all derivatives have also been carried out., 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 Inc. All rights reserved.)

Background: Patients with metabolic dysfunction-associated steatohepatitis (MASH) are at an increased risk of developing venous thromboembolic events (VTE), including deep vein thrombosis (DVT). To date, the study of DVT in MASH has been hampered by the lack of reliable models that mimic the pathological aspects of human disease., Objectives: To evaluate DVT severity and hypercoagulability in murine and human MASH., Methods: Transcriptional changes in the liver, plasma markers of coagulation, and DVT severity were evaluated in mice fed a chow diet or a high-fructose, high-fat, and high-cholesterol, MASH diet for 24 weeks. Plasma analyses of coagulations markers and thrombin generation assay were performed in a well-characterized cohort of patients with or without MASH., Results: Mice fed the MASH diet developed steatohepatitis and fibrosis, mimicking human MASH. Liver RNA-sequencing revealed a significant upregulation of pathways related to inflammation and coagulation concomitant with increased plasma coagulation markers including increased prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor-1 levels, and endothelin 1. MASH exacerbated DVT severity in mice, as evidenced by increased thrombus weight and higher thrombosis incidence (15/15 vs. 11/15 in controls, p=0.0317). Higher endothelin 1 release and increased apoptosis were found in endothelial cells stimulated with supernatants of palmitate-stimulated HepG2 cells. Patients with MASH exhibited increased plasma coagulation markers and delayed thrombin generation., Conclusion: We report enhanced DVT severity and hypercoagulability, both in murine and human MASH. Our model of MASH-DVT can facilitate a better understanding of the fundamental mechanisms leading to increased VTE in patients with MASH., (Copyright © 2024. Published by Elsevier Inc.)

Oceanic phytoplankton productivity, which regulates atmospheric CO 2 , is crucial for unraveling the complexities of the global carbon cycle. Despite its substantial contribution to the global carbon budget and its critical role in anthropogenic carbon sink, the Southern Ocean (SO) remains under-sampled due to logistical challenges. The present study attempts to elucidate the variability of water column primary production (PP) in the Indian Sector of the Southern Ocean (ISSO) by examining associated physicochemical parameters and physiological conditions of phytoplankton that drive this variability. The study revealed the nutrient limitation in the region north of the Subantarctic Front (SAF) and light limitation coupled with intense zooplankton grazing in the region south of the SAF. Coastal waters exhibit higher PP, characterized by the prevalence of large phytoplankton. The SAF displayed maximum productivity among the fronts, while the Polar Front 2 (PF-2) recorded the lowest. The water column PP varies from 27.01 to 960.69 mg C m -2 d -1 in the frontal region, while the coastal waters recorded productivity up to 1083.56 mg C m -2 d -1 . Phytoplankton in the frontal regions indicated a stable surface abundance, except north of the Subtropical Front (STF), where the oligotrophic condition fosters the growth of picoplankton, subjected to high grazing by microzooplankton. Conversely, in the colder coastal waters, the phytoplankton experienced physiological acclimation. Model-based estimates of PP highlighted the efficacy of the Carbon-based Production Model (CbPM) in estimating net PP (NPP) in these polar waters, surpassing the Vertically Generalized Production Model (VGPM) and Eppley-VGPM. Notably, all model-based PP estimates significantly improved with in situ chlorophyll as input instead of satellite-retrieved chlorophyll. While the models performed well in the coastal water, their performance was suboptimal in the frontal region. This study advances our understanding of the intricate dynamics of phytoplankton productivity in the SO, offering valuable insights for future research endeavors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships with other people or organizations that could have appeared to influence (bias) the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Different bone remodeling algorithms are used to predict bone adaptation and to understand how bones respond to the mechanical stimuli altered by implants. This paper introduces a novel micro-scale bone remodeling algorithm, which deviates from conventional methods by focusing on structure-based bone adaptation instead of density-based approaches., Methods: The proposed model simulated cellular activities such as bone resorption, new bone formation, and maturation of newly formed bone. These activities were assumed to be triggered by mechanical stimuli. Model parameters were evaluated for the 3D geometries of trabecular bone from intact femur developed from micro computed tomography (CT) scan data. Two different hip implants, solid and porous were used, and two different bone remodeling methods were performed using the proposed and conventional methods., Results: Results showed that micro CT scan-based finite element (FE) models accurately captured the microarchitecture and anisotropy of trabecular bone. The predicted bone resorption rate at the peri-prosthetic regions for the solid and porous implants was in the range of 17-27% and 4.5-7.3%, respectively, for a simulated period of four years., Conclusions: The results obtained from FE analysis strongly align with clinical findings, confirming the effectiveness of the proposed algorithm. By emphasizing the structural aspect of bone adaptation, the proposed algorithm brings a fresh perspective on bone adaptation at the peri-prosthetic bone. This method can help researchers and clinicians to improve implant designs for better clinical outcomes., 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. Published by Elsevier Ltd.)

A fundamental necessity in advancing sustainable crop production lies in the establishment of a reliable technique for assessing soil health. Soil health assessment is a challenge considering multiple interactions among dynamic indicators within various management strategies and agroecological contexts. Hence a study was conducted to determine the soil health variables, quantify the soil health index (SHI), and validate them with the productivity of rice (Oryza sativa L.)-wheat (Triticum aestivum L.) system for the Indo Gangetic basin of Bihar, India, under four contrasting agro-climatic zones (ACZ-I, II, IIIA & IIIB). For this study, 100 soil samples (0-15 cm) from each ACZ with a total of 400 soil samples were obtained for analyzing 20 soil health variables (soil physical, chemical, and biological properties). To identify SHI and important soil health variables, principal component analysis (PCA) was employed. Apart from specific variables, soil pH, soil organic carbon (SOC), available Zn and available water capacity (AWC) were identified as common indicators for the four ACZs. Results revealed that under the rice-wheat cropping system, ACZ-IIIB soils had a higher SHI (0.19-0.70) than other ACZs. SHI of ACZ-IIIB was significantly influenced by SOC (19.32 %), available P (10.52 %), clay (10.43 %), pH (10.80 %), and soil respiration (9.8 %). The strong relationship between SHI and system productivity of the rice-wheat (R 2  = 0.79) system indicates that the selected soil health variables are representative of good soil health. It is concluded that ACZ-specific SHIs are a promising strategy for evaluating and monitoring soil health to achieve the United Nations' Sustainable Development Goal of 'zero hunger' by 2030., Competing Interests: Declaration of competing interest The authors declare that there are no known competing financial interests or personal relationships that could have influenced this paper's findings., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis-HEME bound complex by Se interacting directly with HEME, and in the T. versicolor-HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor, and T. selenatis, which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study., 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 Inc. All rights reserved.)

Mitochondrial dysfunction and cognitive impairment are widespread phenomena among the elderly, being crucial factors that contribute to neurodegenerative diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular defense systems, including that against oxidative stress. As such, increased Nrf2 activity may serve as a strategy to avert mitochondrial dysfunction and cognitive decline. Scientific data on Nrf2-mediated neuroprotection was collected from PubMed, Google Scholar, and Science Direct, specifically addressing mitochondrial dysfunction and cognitive impairment in older people. Search terms included "Nrf2", "mitochondrial dysfunction," "cognitive impairment," and "neuroprotection." Studies focusing on in vitro and in vivo models and clinical investigations were included to review Nrf2's therapeutic potential comprehensively. The relative studies have demonstrated that increased Nrf2 activity could improve mitochondrial performance, decrease oxidative pressure, and mitigate cognitive impairment. To a large extent, this is achieved through the modulation of critical cellular signalling pathways such as the Keap1/Nrf2 pathway, mitochondrial biogenesis, and neuroinflammatory responses. The present review summarizes the recent progress in comprehending the molecular mechanisms regarding the neuroprotective benefits mediated by Nrf2 through its substantial role against mitochondrial dysfunction and cognitive impairment. This review also emphasizes Nrf2-target pathways and their contribution to cognitive function improvement and rescue from mitochondria-related abnormalities as treatment strategies for neurodegenerative diseases that often affect elderly individuals., 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 Inc. All rights reserved.)

Hydronephrosis, characterized by the dilation of the renal pelvis and calyces, often results from obstructive uropathy, commonly due to ureterolithiasis. However, rare congenital anomalies, such as a retrocaval ureter (RCU)-where the ureter passes behind the inferior vena cava- can also cause hydronephrosis. This case report describes an 11-year-old male presenting with right-sided flank pain and hematuria. Initial ultrasonography and noncontrast CT revealed right hydronephrosis without ureteral stones. Subsequently, contrast-enhanced CT urography found an abnormality in the course of the right ureter behind the inferior vena cava. He was diagnosed with right retrocaval ureter with hydronephrosis, and managed by surgical resection of the retrocaval segment and uretero-ureteral anastomosis. The postoperative course was uneventful. RCU usually presents in the third or fourth decade of life, however, it should be in the differential diagnosis of hydronephrosis in the pediatric population. The diagnosis of RCU is often delayed and missed till advanced imaging like CT urography is sought for unexplained hydronephrosis. If left untreated, it may lead to chronic renal failure. Therefore, emphasis should be placed on timely diagnosis and management of retrocaval ureter., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The present work focuses on the fabrication of polyvinyl alcohol-chitosan-loaded oleanolic acid-nanofibers (PVA-CS-OLA-NFs) for bacterial infection. The prepared PVA-CS-OLA-NFs were characterized for contact angle, SEM, AFM, XRD, FTIR, and TGA. The solid-state characterization and in vitro performance evaluation of nanofibers reveal consistent interconnection and diameters ranging from 102 ± 9.5 to 386 ± 11.6 nm. The nanofibers have a flat surface topography and exhibit efficient drug entrapment. Moreover, the in vitro release profile of PVA-CS-OLA-NFs was found to be 51.82 ± 1.49 % at 24 h. Furthermore, the hemocompatibility study showed that the developed PVA-CS-OLA-NFs are non-hemolytic to human blood. The PVA-CS-OLA-NFs demonstrate remarkable antibacterial capabilities, as evidenced by their MBC and MIC values, which range from 128 and 32 μg/mL, against the strains of S. aureus. The in-vivo fluorescence optical imaging showed the sustained PVA-CS-OLA-NFs release at the wound site infected with S. aureus for a longer duration of time. Moreover, the PVA-CS-OLA-NFs showed superior wound healing performance against S. aureus infected wounds compared to the marketed formulation. Further, the laser Doppler imaging system improved oxygen saturation, blood supply, and wound healing by providing real-time blood flow and oxygen saturation information., 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 B.V. All rights reserved.)

In the realm of plant biology, understanding the intricate regulatory mechanisms governing stress responses stands as a pivotal pursuit. Circular RNAs (circRNAs), emerging as critical players in gene regulation, have garnered attention in recent days for their potential roles in abiotic stress adaptation. A comprehensive grasp of circRNAs' functions in stress response offers avenues for breeders to manipulating plants to develop abiotic stress resistant crop cultivars to thrive in challenging climates. This study pioneers a machine learning-based model for predicting abiotic stress-responsive circRNAs. The K-tuple nucleotide composition (KNC) and Pseudo KNC (PKNC) features were utilized to numerically represent circRNAs. Three different feature selection strategies were employed to select relevant and non-redundant features. Eight shallow and four deep learning algorithms were evaluated to build the final predictive model. Following five-fold cross-validation process, XGBoost learning algorithm demonstrated superior performance with LightGBM-chosen 260 KNC features (Accuracy: 74.55 %, auROC: 81.23 %, auPRC: 76.52 %) and 160 PKNC features (Accuracy: 74.32 %, auROC: 81.04 %, auPRC: 76.43 %), over other combinations of learning algorithms and feature selection techniques. Further, the robustness of the developed models were evaluated using an independent test dataset, where the overall accuracy, auROC and auPRC were found to be 73.13 %, 72.34 % and 72.68 % for KNC feature set and 73.52 %, 79.53 % and 73.09 % for PKNC feature set, respectively. This computational approach was also integrated into an online prediction tool, AScirRNA (https://iasri-sg.icar.gov.in/ascirna/) for easy prediction by the users. Both the proposed model and the developed tool are poised to augment ongoing efforts in identifying stress-responsive circRNAs in plants., 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.)

The bromodomain and extraterminal (BET) family of proteins show altered expression across various cancers. The members of the bromodomain (BRD) family contain epigenetic reader domains that bind to acetylated lysine residues in both histone and non-histone proteins. Since BRD proteins are involved in cancer initiation and progression, therapeutic targeting of these proteins has recently been an area of interest. In experimental settings, JQ1, a commonly used BRD inhibitor, is the first known inhibitor to target BRD-containing protein 4 (BRD4), a ubiquitously expressed BRD and extraterminal family protein. BRD4 is necessary for a normal cell cycle, and its aberrant expression activates pro-inflammatory cytokines, leading to tumor initiation and progression. Various BRD4 inhibitors have been developed recently and tested in preclinical settings and are now in clinical trials. However, as with many targeted therapies, BRD inhibitor treatment can lead to resistance to treatment. Here, we investigated the kinases up-regulated on JQ1 treatment that may serve as target for combination therapy along with BRD inhibitors. To identify kinase targets, we performed a comparative analysis of gene expression data using RNA from BRD inhibitor-treated cells or BRD-modulated cells and identified overexpression of several kinases, including FYN, NEK9, and ADCK5. We further validated, by immunoblotting, the overexpression of FYN tyrosine kinase; NEK9 serine/threonine kinase and ADCK5, an atypical kinase, to confirm their overexpression after BRD inhibitor treatment. Importantly, our studies show that targeting FYN or NEK9 along with BRD inhibitor effectively reduces proliferation of cancer cells. Therefore, our research emphasizes a potential approach of utilizing inhibitors targeting some of the overexpressed kinases in conjunction with BRD inhibitors to enhance therapeutic effectiveness., 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. Published by Elsevier Inc.)

Background: Hip-spine syndrome (HSS) was first described in 1983 to describe the symptomatology resulting from concomitant lumbar degenerative stenosis and hip osteoarthritis. Numerous studies have sought to understand the underlying pathology and appropriate management of this syndrome. The purpose of this article is to review the literature for the specific imaging characteristics and the optimal surgical treatment of HSS., Methods: A systematic review was conducted via an electronic database search through PubMed to identify all publications related to HSS. All publications that contained data on patients who underwent surgical treatment for HSS and reported patient-reported outcome measures or radiographic data were included. Exclusion criteria consisted of publications in a language other than English, review articles, and technique articles., Results: Fifteen articles that focused on the surgical management of HSS were identified. Of these 15 articles, 8 reported radiographic outcomes, with most reporting no significant change in spinopelvic parameters before and after surgery. Thirteen articles reported clinical outcomes, with 8 of those 13 articles identifying patient-reported outcome measures to be significantly improved following surgery., Conclusions: The data on the surgical management of HSS remains sparse. While there is some evidence that total hip arthroplasty in patients who previously underwent spinal fusion may have higher complication rates, there remains debate regarding which surgical problem to address first, the hip or the spine., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Declaration of competing interest Authors declare no conflict of interests.

SRY (Sex Determining Region) box 2 (SOX2) is an essential transcription factor that plays crucial roles in activating genes involved in pre- and post-embryonic development, adult tissue homeostasis, and lineage specifications. SOX2 maintains the self-renewal property of stem cells and is involved in the generation of induced pluripotency stem cells. SOX2 protein contains a particular high-mobility group domain that enables SOX2 to achieve the capacity to participate in a broad variety of functions. The information about the involvement of SOX2 with gene regulatory elements, signaling networks, and microRNA is gradually emerging, and the higher expression of SOX2 is functionally relevant to various cancer types. SOX2 facilitates the oncogenic phenotype via cellular proliferation and enhancement of invasive tumor properties. Evidence are accumulating in favor of three dimensional (higher order) folding of chromatin and epigenetic control of the SOX2 gene by chromatin modifications, which implies that the expression level of SOX2 can be modulated by epigenetic regulatory mechanisms, specifically, via DNA methylation and histone H3 modification. In view of this, and to focus further insights into the roles SOX2 plays in physiological functions, involvement of SOX2 during development, precisely, the advances of our knowledge in pre- and post-embryonic development, and interactions of SOX2 in this scenario with various signaling pathways in tumor development and cancer progression, its potential as a therapeutic target against many cancers are summarized and discussed in this article., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Psoriasis is a chronic, non-communicable condition of the skin with an immune-mediated etiology. Periodontitis is a chronic inflammatory disease of the tooth-supporting tissues and is now recognized as an established risk factor for various systemic diseases. The present observational study aims to assess the prevalence of periodontitis and its related indices in individuals with psoriasis and to compare them with individuals without psoriasis. A cross-sectional case-control study was performed in a hospital setting, including 200 diagnosed cases of psoriasis and 200 age- and sex-matched healthy controls., Methods: The case group included patients diagnosed with psoriasis (defined as ICD-10 L40.0-L40.9) by a trained dermatologist. Controls included age- and sex-matched healthy individuals. After history-taking, a detailed dermatological and periodontal examination was done for all the enrolled subjects. The results were statistically analyzed using SPSS software., Results: The study group had a significantly higher mean GI, PI, PPD and CAL in comparison to the controls. Psoriasis patients had significantly greater scores for GI and PI (1.68 ± 0.61 and 1.57 ± 0.54, respectively) as compared to controls (1.48 ± 0.56 and 1.39 ± 0.60, respectively). Periodontitis was also found to be more prevalent among the cases. Stage II and Stage III periodontitis were found in 41.0 % of cases and 30.5 % of controls, while 12.5 % of cases and 6.0 % of controls had stage IV periodontitis. This difference was statistically significant., Conclusion: An association between psoriasis and periodontitis was found in the present study, as the individuals with psoriasis had a higher severity and prevalence of periodontitis., Competing Interests: The authors report no conflict of interest related to the study. No funding or material support was received for the study., (© 2024 The Authors.)

Mixed-lineage kinase 3 (MLK3) is a serine/threonine kinase of the MAPK Kinase kinase (MAP3K) family that plays critical roles in various biological processes, including cancer. Upon activation, MLK3 differentially activates downstream MAPKs, such as JNK, p38, and ERK. In addition, it regulates various non-canonical signaling pathways, such as β-catenin, AMPK, Pin1, and PAK1, to regulate cell proliferation, apoptosis, invasion, and metastasis. Recent studies have also uncovered other potentially diverse roles of MLK3 in malignancy, which include metabolic reprogramming, cancer-associated inflammation, and evasion of cancer-related immune surveillance. The role of MLK3 in cancer is complex and cancer-specific, and an understanding of its function at the molecular level aligned specifically with the cancer hallmarks will have profound therapeutic implications for diagnosing and treating MLK3-dependent cancers. This review summarizes the current knowledge about the effect of MLK3 on the hallmarks of cancer, providing insights into its potential as a promising anticancer drug target., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Published by Elsevier B.V.)

Nickel-titanium (NiTi) rotary files used in root canal treatments experience fatigue and shear damage due to the complex curved geometries and operating conditions encountered within the root canal. This can lead to premature file fracture, causing severe complications. A comprehensive understanding of how different factors contribute to file damage is crucial for improving their functional life. This study investigates the combined effects of root canal curvature radius, file canal curvature, and rotational speed on the fatigue life and failure modes of NiTi endodontic files through an integrated computational and experimental approach. Advanced finite element simulations precisely replicating the dynamic motion of files inside curved canal geometries were conducted. Critical stress/strain values were extracted and incorporated into empirical fatigue models to predict the functional life of endodontic files. Extensive experiments with files rotated inside artificial curved canals at various canal curvatures and speeds provided validation. Increasing the canal curvature beyond 60 ∘ and shorter curvature radii below 5 mm dramatically reduced the functional life of the endodontic file, especially at rotational speeds over 360 rpm. The Coffin-Manson fatigue model based on strain amplitude showed the closest agreement with experiments. Shear stresses dominated damage at low canal curvatures, while the combined shear-fatigue loading effects were prominent at higher canal curvatures. This conclusive study elucidates how operational parameters like canal curvature radii, canal curvature, and rotational speed synergistically influence the fatigue damage processes in NiTi files. The findings offer valuable guidelines to optimize these factors, significantly extending the functional life of endodontic files and reducing the risk of intra-operative failures. The validated computational approach provides a powerful tool for virtual testing and estimation of the functional life of the new file designs before manufacturing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sahil Kalra has patent Scotch Yoke Mechanism Based Cyclic Fatigue Testing Device for Rotary Endodontic Files pending to 202311042833. If there are other authors, they 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.)

Background: Ascites in children is multifactorial and serum ascites albumin gradient (SAAG) ≥1.1 helps differentiate portal hypertension (PHTN) related from non-PHTN ascites., Aims: We evaluated the aetiology and diagnostic accuracy of SAAG in children with ascites., Methods: Children with ascites were retrospectively evaluated. Etiological diagnosis was based on clinical presentation and investigations. All cases with ascitic fluid analysis and a definite diagnosis were included for calculating the utility of SAAG., Results: We enrolled 878 children (568[64.7%] boys). Majority were PHTN related (638[72.7%]) and secondary to acute viral hepatitis (98,15.4%), acute liver failure (185,29%), chronic liver disease (276,43.3%) and Budd-Chiari syndrome (79,12.4%). Other causes included tubercular (46,5.2%), pancreatic (32,3.6%), chylous (20,2.3%), biliary (12,1.4%), pseudoascites (16,1.8%), infections (46,5.2%), nephrotic (26,2.9%), malignancy (23,2.6%), cardiac (9,1.0%) and others (10,1%). SAAG (n = 305) correctly differentiated PHTN and non-PHTN ascites in 272 (89.2%) cases, with a high sensitivity (97%), specificity (93%) and diagnostic accuracy (95.8%). Reasons for inaccurate SAAG included mixed ascites (n = 9), different day serum and ascitic fluid albumin estimation (n = 5), serum albumin ≤1.1 g/dL (n = 2), chylous ascites (n = 3), hypergammaglobulinemia (n = 1), albumin infusions (n = 1) and unexplained (n = 12)., Conclusions: Nearly 27% children had non-PHTN related ascites. SAAG differentiates PHTN from non-PHTN ascites with a diagnostic accuracy of 95%., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to be disclosed, (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Quantum dots (QDs), a novel category of semiconductor materials, exhibit extraordinary capabilities in tuning optical characteristics. Their emergence in biophotonics has been noteworthy, particularly in bio-imaging, biosensing, and theranostics applications. Although conventional QDs such as PbS, CdSe, CdS, and HgTe have garnered attention for their promising features, the presence of heavy metals in these QDs poses significant challenges for biological use. To address these concerns, the development of Ag chalcogenide QDs has gained prominence owing to their near-infrared emission and exceptionally low toxicity, rendering them suitable for biological applications. This review explores recent advancements in Ag chalcogenide QDs, focusing on their synthesis methodologies, surface chemistry modifications, and wide-ranging applications in biomedicine. Additionally, it identifies future directions in material science, highlighting the potential of these innovative QDs in revolutionizing the field., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Context: Pre-diabetes is a significant public health problem worldwide. India has a very high rate of progression from pre-diabetes to diabetes, 75-78 per thousand persons per year., Objective: To study the efficacy of individualized homeopathic medicinal products (HMPs) against placebos in preventing the progression from pre-diabetes to diabetes., Design: Six-month, double-blind, randomized (1:1), two parallel arms, placebo-controlled trial., Setting: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India., Patients: Sixty participants with pre-diabetes., Interventions: Verum: HMPs plus yoga therapy (YT; n = 30); control: identical-looking placebos plus YT (n = 30)., Main Outcome Measures: The primary efficacy endpoint was the proportion of participants progressing from pre-diabetes to diabetes, measured after three and six months. Secondary outcomes comprised of fasting blood glucose (FBS), oral glucose tolerance test (OGTT), glycated hemoglobin percentage (HbA1c%), lipid profile, liver enzymes (alanine transaminase, aspartate transaminase), urea and creatinine, and Measure Yourself Medical Outcome Profile version 2 (MYMOP-2); all measured after 3 and 6 months., Results: The proportion of participants converted from pre-diabetics to diabetics (n/N; n = diabetics, N = prediabetics) was significantly less in the verum group than control: HbA1C% (month 3: verum - 2/30 versus control - 11/30, p = 0.003; month 6: 3/30 vs. 2/30, p = 0.008), OGTT (month 3: 0/30 vs. 8/30, p = 0.015; month 6: 0/30 vs. 1/30, p = 0.008), but not according to FBS (month 3: 1/30 vs. 1/30, p = 0.779; month 6: 1/30 vs. 3/30, p = 0.469). Several secondary outcomes also revealed significant improvements in the verum group than in placebo: HbA1C% (p < 0.001), OGTT (p = 0.001), serum ALT (p = 0.031), creatinine (p = 0.012), and MYMOP-2 profile scores (p < 0.001). Sulphur, Bryonia alba, and Thuja occidentalis were the most frequently indicated medicines. Thus, HMPs outperformed placebos by successfully preventing the progression of pre-diabetes to diabetes., Trial Registration: Clinical Trials Registry - India CTRI/2022/04/042,026; UTN: U1111-1277-0021., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Splendid Unmanned Aerial Vehicle (UAV) applications upshot its enormous use in densely inhabited areas, which is a matter of concern. In such areas, a proper tracking system is required to track an unauthorized/invader drone to ensure safety. With the flexibility of reaching inaccessible places, an Unmanned Aerial Vehicle Mounted Adaptable Radar Antenna Array (UAVMARAA) could be used. In this regard, a Hybrid Unscented Kalman-Continuous Ant Colony Filter (HUK-CACF) is proposed to estimate the position of the invader drone efficiently. Simulation results demonstrate the efficiency and robustness of the proposed filter for tracking system compared to the existing filters in terms of success rate. Further, for various Adaptable Radar Antenna Array (ARAA) patterns such as Uniform Linear Array (ULA), Uniform Rectangular Array (URA), and Uniform Circular Array (UCA), analysis is done for pertaining actual tracking effect for various parameters such as bearing, Doppler shift, ranging, and Radar Cross Section (RCS) by considering wobbling and mutual coupling (MC) effect. The result shows that the proposed filter outperforms in all the scenarios. Among the various ARAA, URA performs better than the other configurations., 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 ISA. Published by Elsevier Ltd. All rights reserved.)

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT)., Materials and Methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function., Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively ( P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months ( P  = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively ( P -0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients ( P -0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively ( P -<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis., Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Heavy metal contamination of aquatic environments adversely affects the health of aquatic organisms and consumption of fish contaminated with heavy metals poses serious health risks to humans. Among various strategies, probiotics (living microorganisms known to have beneficial effects on the host), which have been extensively applied in the aquaculture industry, could be helpful for heavy metal detoxification and remediation. Several probiotics, including Lactobacillus strains, exhibit heavy metal binding, high heavy metal tolerance, and other beneficial characteristics for the host. Notably, numerous probiotics have been reported to bind heavy metals and excrete them from the host. Various probiotic strains (Lactobacillus, Bacillus, Lactococcus, etc.) show beneficial effects in alleviating heavy metal toxicity in cultured fish species. Certain probiotic bacteria reduce the absorption and bioavailability of heavy metals by enhancing heavy metal detoxification and sequestration while preserving gut barrier function. This review summarises the toxic effects of selected heavy metals on the health of farmed fish and discusses the role of probiotic strains in remediating the consequential exposure-induced immune toxicity and oxidative stress. Moreover, we discussed the protective strategies of probiotics against heavy metal accumulation in various tissues and gut dysbiosis in fish to alleviate heavy metal toxicity in fish farming, thereby promoting a sustainable blue economy worldwide., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Se Chang Park reports article publishing charge was provided by Companion Animal Research of the Rural Development Administration, Republic of Korea., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule., Competing Interests: Declaration of competing interest The authors of the manuscript “Computational and Biological Approaches in Repurposing Ribavirin for Lung Cancer Treatment: Unveiling Antitumorigenic Strategies”, submitted to the journal “Life Sciences”, have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Small RNA (sRNA) in bacteria serve as the key messengers in regulating genes associated with quorum sensing controlled bacterial virulence. This study was aimed to unveil the regulatory role of sRNA PA0730.1 on the expression of various traits of Pseudomonas aeruginosa linked to pathogenicity, with special emphasis on the growth, colony morphology, cell motility, biofilm formation, and the expression of diverse virulence factors. PA0730.1 sRNA was found to be upregulated both during planktonic stationary growth phase and at biofilm state of P. aeruginosa PAO1. PA0730.1 deleted strain showed significant growth retardation with increased doubling time. Overexpression of PA0730.1 led to enhanced motility and biofilm formation, while the ∆PA0730.1 strain displayed significant inhibition in motility and biofilm formation. Furthermore, PA0730.1 was found to regulate the synthesis of selected virulence factors of P. aeruginosa. These observations in PA0730.1 + and ∆PA0730.1 were found to be correlated with the PA0730.1-mediated repression of transcription regulators, mucA and rpoS, both at transcriptional and translational levels. The results suggest that PA0730.1 sRNA might be a promising target for developing new drug to counter P. aeruginosa pathogenesis, and could also help in RNA oligonucleotide based therapeutic research for formulating a novel therapeutant., 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. Published by Elsevier B.V.)

We performed an international retrospective cohort study to investigate the prognostic impact of cytogenetic abnormalities by FISH in 283 patients with AL amyloidosis treated with frontline daratumumab-bortezomib-cyclophosphamide-dexamethasone (Dara-VCD) or Dara-VD. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) [hereafter, +1q], hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The endpoints of interest were rate of hematologic complete response (heme CR), very good partial response or better (≥VGPR), and hematologic event-free survival (Heme EFS). The incidence of abnormalities was following: t(11;14)-53.4%; deletion (13q)-28.9%; +1q-22.3%; hyperdiploidy-19.4%; HR translocations-6.6%; and deletion(17p)-4.5%. The heme-CR rate by cytogenetic subgroups were: t(11;14) vs no t(11;14)-45.2% vs 41.8% (p=0.597); del(13q) vs no del(13q)-46.8% vs 42.8% (p=0.594); +1q vs no +1q-30.2% vs 47.9% (p=0.022); hyperdiploidy vs no hyperdiploidy-39.5% vs 44.9% (p=0.541); HR translocations vs none: 45.5% vs 43.1% (p=0.877); and del(17p) vs no del(17p)-50.0% vs 42.9% respectively (p=0.658). Similarly, +1q was the only subgroup with a significantly lower ≥VGPR rate (64.2% vs 79.0%; p=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year OS was 80.98% (95% CI, 75.6-85.4). The presence of+1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; p=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel immunotherapies frontline should be enriched in +1q to further improve outcomes in this subgroup., (Copyright © 2024 American Society of Hematology.)

The present study adopts a multi-facet approach to design bio inspired concentrated alloys for potential application as articulating surfaces in joint replacements. A series of equiatomic, Nb rich and Ti rich TiMoNbZr based medium entropy alloys (MEAs) were processed via arc melting and their mechanical, in-vitro corrosion, wear, and in vitro and in vivo biocompatibility were investigated. Equiatomic MEA had primarily bcc with minor hcp phases where the single bcc was achieved with the addition of Nb. The single bcc Nb rich alloy resulted in 13 % elongation, much higher than equiatomic or Ti rich alloy. All the MEAs showed comparatively higher yield strength due to the climb of edge dislocations which is the main rate limiting mechanism at 300 K, as evident molecular dynamics (MD) simulation. The locally fluctuating energy landscape promotes kinks on edge dislocation, and at local minima nanoscale segments gets pinned. Upon yielding the entangled kink leaves a trail of vacancies/interstitials and escapes via climb motion to render high yield strength. The higher corrosion and pitting resistance of Nb enriched alloys can be attributed to the stable ZrO 2 , Nb 2 O 5 , TiO 2 , and MoO 3 oxides, high polarization resistance (10 6 -10 5 Ωcm -2 ), and low defect densities (10 16 -10 18 ). In vitro cell-materials interaction using MC3T3-E1 showed bioinert but cytocompatible nature of the MEAs. The wear rate of the MEAs was in the range of 7-9 × 10 -5 mm 3 N -1 m -1 . The wear debris did not show any tissue necrosis when implanted in rabbit femur rather new bone regeneration can be seen around the particles. STATEMENT OF SIGNIFICANCE: In the present work, a noble Nb enriched MEAs with superior mechanical, in vitro wear, corrosion and cytocompatibility properties was designed for articulating surfaces in joint replacement., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Beta-casomorphins (BCMs) are the bio-active peptides having opioid properties which are formed by the proteolytic digestion of β-caseins in milk. BCM-7 forms when A1 milk is digested in the small intestine due to a histidine at the 67th position in β-casein, unlike A2 milk, which has proline at this position and produces BCM-9. BCM-7 has further degraded into BCM-5 by the dipeptidyl peptidase-IV (DPP-IV) enzyme in the intestine. The opioid-like activity of BCM-7 is responsible for eliciting signaling pathways which enable a wide range of physiological effects. The aim of our study was to find out the differential role of BCMs (BCM-7, BCM-9 and BCM-5) on pancreatic β-cell proliferation, insulin secretion, and opioid peptide binding receptors from β-cells (RIN-5F cell line) in normal (5.5 mM) and high glucose (27.5 mM) concentrations. Our results showed that BCM-7/9/5 did not affect β-cell viability, proliferation, and insulin secretion at normal glucose level. However, at higher glucose concentration, BCMs significantly protected β-cells from glucotoxicity but did not affect the insulin secretion. Interestingly, in the presence of Mu-opioid peptide receptor antagonist CTOP, BCMs did not protect β-cells from glucotoxicity. The results suggest that BCMs protect β-cells from glucotoxicity via non-opioid mediated pathways because BCMs did not modulate the gene expression of the mu, kappa and delta opioid peptide receptors., 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. Published by Elsevier Inc.)

Onion peels (OP) are byproduct of food processing industries that poses economic and environmental challenges. However, being rich source of bioactive compounds like Quercetin (Qt), a polyphenolic antioxidant with potential health benefits, harnessing value from such waste can imbibe sustainable practices and protect environment. With this view, the present study targets selective recovery of Qt from OP waste using rationally designed molecularly imprinted polymer (MIP). Density Functional Theory (DFT) was used for the theoretical selection of the best conformer of Qt (template), methacrylic acid (MAA) as functional monomer, ratio of Qt-MAA for getting stable pre-polymerization complex, and to avoid hit and trial experiments. The theoretical results were validated experimentally by synthesizing MIP/ control polymer (NIP) using MAA as functional monomer, EGDMA as a cross-linker and AIBN as initiator. Synthesized MIP/NIP were characterized using various characterization techniques to confirm successful imprinting. Prepared MIP and NIP could effectively rebind the Qt molecule with binding capacity of 46.67 and 20.89 mg g -1 respectively. Furthermore, synthesized MIP could selectively recover 62.81 % of Qt from 1 g of dry onion peel powder. This study can be effectually used for sustainable recovery of Qt in large scale for various foods, cosmetic and pharmaceutical applications., 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 B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a mainstream halting liver disease with high prevalence in North America, Europe, and other world regions. It is an advanced form of NAFLD caused by the amassing of fat in the liver and can progress to the more severe form known as non-alcoholic steatohepatitis (NASH). Until recently, there was no authorized pharmacotherapy reported for NASH, and to improve the patient's metabolic syndrome, the focus is mainly on lifestyle modification, weight loss, ensuring a healthy diet, and increased physical activity; however, the recent approval of Rezdiffra (Resmetirom) by the US FDA may change this narrative. As per the reported studies, there is an increased articulation of uptake and efflux transporters of the liver, including OATP and MRP, in NASH, leading to changes in the drug's pharmacokinetic properties. This increase leads to alterations in the pharmacokinetic properties of drugs. Furthermore, modifications in Cytochrome P450 (CYP) enzymes can have a significant impact on these properties. Xenobiotics are metabolized primarily in the liver and constitute liver enzymes and transporters. This review aims to delve into the role of metabolism, transport, and potential herb-drug interactions in the context of NASH., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts with anyone or any institute., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 μg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 μg/m³ (24 h) by 27-34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention., 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 Inc. All rights reserved.)

Even though the genus Mycobacterium is a diverse group consisting of a majority of environmental bacteria known as non-tuberculous mycobacteria (NTM), it also contains some of the deadliest pathogens (Mycobacterium tuberculosis) in history associated with chronic disease called tuberculosis (TB). Formation of biofilm is one of the unique strategies employed by mycobacteria to enhance their ability to survive in hostile conditions. Biofilm formation by Mycobacterium species is an emerging area of research with significant implications for understanding its pathogenesis and treatment of related infections, specifically TB. This review provides an overview of the biofilm-forming abilities of different species of Mycobacterium and the genetic factors influencing biofilm formation with a detailed focus on M. tuberculosis. Biofilm-mediated resistance is a significant challenge as it can limit antibiotic penetration and promote the survival of dormant mycobacterial cells. Key genetic factors promoting biofilm formation have been explored such as the mmpL genes involved in lipid transport and cell wall integrity as well as the groEL gene essential for mature biofilm formation. Additionally, biofilm-mediated antibiotic resistance and pathogenesis highlighting the specific niches, sites of infection along with the possible mechanisms of biofilm dissemination have been discussed. Furthermore, drug targets within mycobacterial biofilm and their role as potential biomarkers in the development of rapid diagnostic tools have been highlighted. The review summarises the current understanding of the complex nature of Mycobacterium biofilm and its clinical implications, paving the way for advancements in the field of disease diagnosis, management and treatment against its multi-drug resistant species., 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 Inc. All rights reserved.)

Objective: This study aimed to explore the therapeutic potential of medicinal herbs for chronic periodontitis by examining the molecular interactions between specific herbal compounds and the heme-binding protein of Porphyromonas gingivalis, a key pathogen involved in the disease., Methods: The crystal structure of heme-binding protein was obtained from the Protein Data Bank. Herbal compounds were identified through an extensive literature review. Molecular docking simulations were performed to predict binding affinities, followed by Absorption, Distribution, Metabolism, and Excretion (ADME) parameter prediction. Drug-likeness was assessed based on Lipinski's Rule of Five, and pharmacophore modeling was conducted to identify key molecular interactions., Results: The molecular docking simulations revealed that chelidonine, rotenone, and myricetin exhibited significant binding affinities to the heme-binding protein, with docking scores of -6.5 kcal/mol, -6.4 kcal/mol, and -6.1 kcal/mol, respectively. These compounds formed stable interactions with key amino acid residues within the binding pocket. ADME analysis indicated that all 3 compounds had favourable pharmacokinetic properties, with no violations of Lipinski's rules and minimal predicted toxicity. Pharmacophore modeling further elucidated the interaction profiles, highlighting specific hydrogen bonds and hydrophobic interactions critical for binding efficacy., Conclusions: Chelidonine, rotenone, and myricetin emerged as promising therapeutic candidates for chronic periodontitis due to their strong binding affinities, favorable ADME profiles, and lack of significant toxicity. The detailed pharmacophore modeling provided insights into the molecular mechanisms underpinning their inhibitory effects on the heme-binding protein of P. gingivalis. These findings suggest that these compounds have the potential for further development as effective treatments for chronic periodontitis. Future research should focus on in vitro and in vivo validation of these findings to confirm the efficacy and safety of these compounds in biological systems., Competing Interests: Conflict of 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 Inc. All rights reserved.)

Pseudomonas aeruginosa, an opportunistic bacterial pathogen of public health concern, is known for its metabolic versatility, adaptability in harsh environment, and pathogenic aggressiveness. P. aeruginosa relies on various regulatory networks modulated by small non-coding RNAs, which in turn influence different physiological traits such as metabolism, stress response, and pathogenesis. In this study, srbA sRNA has been shown to play a diverse role in regulating cellular metabolism and the production of different virulence factors in P. aeruginosa. srbA was found to control the TCA cycle, a key regulatory pathway for cellular metabolism and energy production, by regulating three main enzymes: citrate synthase (gltA), isocitrate dehydrogenase (icd), and α-ketoglutarate dehydrogenase E1 subunit (sucA) at both the transcriptional and translational levels. By modulating the TCA cycle, srbA could help the bacteria to adapt nutritional stress by lowering energy consumption. Additionally, srbA has been found to differentially regulate production of various virulence factors such as rhamnolipid, elastase, LasA protease, and pyocyanin under both nutrient-rich and nutrient-limiting conditions. It could also influence motilities in P. aeruginosa, linked to biofilm formation and pathogenicity. Thus, srbA might hold a promise in the research area for identifying virulence pathways and developing novel therapeutic targets to combat the global pathogenic threat of P. aeruginosa., 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 Inc. All rights reserved.)