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Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-β1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Simultaneous positron emission tomography (PET)/magnetic resonance imaging provides concurrent information about anatomic, functional, and molecular changes in disease. We are developing a second generation MR-compatible RF-penetrable TOF-PET insert. The insert has a smaller scintillation crystal size and ring diameter compared to clinical whole-body PET scanners, resulting in higher spatial resolution and sensitivity. This paper reports the initial system performance of this full-ring PET insert. The global photopeak energy resolution and global coincidence time resolution, 11.74 ± 0.03 % FWHM and 238.1 ± 0.5 ps FWHM, respectively, are preserved as we scaled up the system to a full ring comprising 12, 288 LYSO-SiPM channels (crystal size: 3.2 × 3.2 × 20 mm 3 ). Throughout a ten-hour experiment, the system performance remained stable, exhibiting a less than 1% change in all measured parameters. In a resolution phantom study, the system successfully resolved all 2.8 mm diameter rods, achieving an average VPR of 0.28 ± 0.08 without TOF and 0.24 ± 0.07 with TOF applied. Moreover, the implementation of TOF in the Hoffman phantom study also enhanced image quality. Initial MR compatibility studies of the full PET ring were performed with it unpowered as a milestone to focus on looking for material and geometry-related artifacts. During all MR studies, the MR body coil functioned as both the transmit and receive coil, and no observable artifacts were detected. As expected, using the body coil also as the RF receiver, MR image signal-to-noise ratio exhibited degradation (∼30%), so we are developing a high quality receive-only coil that resides inside the PET ring., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Geranyl acetate, a compound found in plant oils, has been studied for its potential effects on renal and cardiovascular ailments., Objective: This study aimed to investigate the diuretic and anti-hyperuricemic properties of geranyl acetate in male Wistar rats using a hyperuricemia-induced rat model., Methods: Molecular docking studies were conducted to assess geranyl acetate's interactions with various targets. in vitro studies were performed to evaluate its scavenging ability and inhibition of xanthine oxidase, urease, and acetylcholinesterase. Subsequently, we administered different doses of geranyl acetate (25, 50, and 100 mg/kg) and a reference drug (furosemide) to the rats to assess their acute and repeated dose diuretic effects over seven days. To understand the diuretic mechanism, we used inhibitors, such as L-- NAME, indomethacin, and atropine, prior to administering geranyl acetate. We also tested the anti-hyperuricemic potential of geranyl acetate on hyperuricemic rats., Results: Molecular docking suggested strong binding between geranyl acetate and nitric oxide synthase. in vitro studies showed significant free radical scavenging activity and and inhibition of acetylcholinesterase, xanthine oxidase, and urease. The 100 mg/kg dose exhibited the most promising diuretic effects, with nitric oxide appearing to influence its action. Uric acid excretion increased at this dose, resembling allopurinol effects., Conclusion: Geranyl acetate has demonstrated significant diuretic and anti-hyperuricemic effects, likely influenced by nitric oxide release and inhibition of enzymes, like xanthine oxidase and urease. The findings have suggested potential benefits for individuals with kidney ailments, hypertension, and gout., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess long-term clinical outcomes and factors associated with target vessel revascularisation in patients with deferred revascularisation based on negative fractional flow reserve and negative instantaneous wave-free ratio., Methods: The longitudinal, retrospective study was conducted from July 1, 2020, to January 1, 2022, at the Aga Khan University Hospital, Karachi, and comprised medical records from January 2012 to January 2020 of patients with deferred revascularisation having intermediate to severe coronary lesions on coronary angiogram and had negative fractional flow reserve >0.80 or instantaneous wave-free ratio >0.89 and had not undergone immediate or planned revascularisation on the basis of negative physiological assessment. Data was collected from the institutional records, while final follow-up was taken by reviewing the medical records or telephonic interviews regarding any major adverse cardiac event after the index procedure. Data was analysed using Stata 14.2., Results: Of the 345 patients, 245(71%) were males. The overall mean age was 62±11 years. There were 194(56%) patients who presented with stable angina and 151(44%) presented with acute coronary syndrome. Mean fractional flow reserve was 0.87±0.04 and mean instantaneous wave-free ratio was 0.93±0.03. Multivessel disease was present in 223(65%) patients. Median follow-up period was 29 months (IQR: 24-36 months). Major adverse cardiovascular events occurred in 22(6%) patients, and target vessel revascularisation was required in 11(3%). Diabetes and percentage of stenosis were found to be independent predictors of major adverse cardiovascular events (p<0.05)., Conclusions: Deferral of revascularisation and opting for medical treatment for coronary artery stenosis with higher fractional flow reserve or instantaneous wave-free ratio could be considered a safe and reasonable strategy.

The article details a feasibility study of removing Brilliant Green (BG), a mutagenic dye from an aqueous solution by adsorption using low-cost coriander seed spent as a by-product in the nutraceutical industry. The study includes an analysis of the parameters that affect the adsorption process. The variables that have been identified include pH, dye concentration, process temperature, adsorbent amount, and particle size of the adsorbent. To obtain information on the adsorption process and to design the mechanism of the adsorption system on experimental equilibrium, 10 isotherm models, namely, Langmuir, Freundlich, Jovanovic, Dubinin-Radushkevich, Sips, Redlich-Peterson, Toth, Vieth-Sladek, Brouers-Sotolongo, and Radke-Prausnitz were applied. It was discovered that the experimental adsorption capacity, q e , was roughly 110   mg g -1 . The result has a maximum adsorption of 136.17 mg g -1 as predicted by Dubinin-Radushkevich isotherm. Diffusion film models, Dumwald-Wagner and Weber-Morris models, and pseudo-first- and second-order models, were used to determine the adsorption kinetics. It was realized that the adsorption kinetics data fit into a pseudo-second-order model. Thermodynamic analysis with a reduced enthalpy change suggests a physical process. The values of the thermodynamic parameters Δ G 0 , Δ H 0 , and Δ S 0 demonstrated an endothermic and nearly spontaneous process of adsorption. The small valuation of Δ H 0 specifies that the process is physical. FTIR spectroscopy and SEM imaging were used to confirm that the BG dye had been adsorbing on the adsorbent surface. The study concludes that NICSS is an effective adsorbent to extract BG dye from wastewater solutions, offers insights into numerous dye and adsorbent interaction possibilities and indicates that the process can be scaled to fit into the concept of circular economy.

Newcastle disease virus (NDV) is a highly infectious viral disease that impacts birds globally, especially domestic poultry. NDV is a type of avian paramyxovirus which poses a major threat to the poultry industry due to its ability to inflict significant economic damage. The membrane protein, Hemagglutinin-Neuraminidase (HN) of NDV is an attractive therapeutic candidate. It contributes to pathogenicity through various functions, such as promoting fusion and preventing viral self-agglutination, which allows for viral spread. In this study, we used pharmacophore modeling to identify natural molecules that can inhibit the HN protein of NDV. Physicochemical characteristics and phylogenetic analysis were determined to elucidate structural information and phylogeny of target protein across different species as well as members of the virus family. For structural analysis, the missing residues of HN target protein were filled and the structure was evaluated by PROCHECK and VERIFY 3D. Moreover, shape and feature-based pharmacophore model was employed to screen natural compounds' library through numerous scoring schemes. Top 48 hits with 0.8860 pharmacophore fit score were subjected towards structure-based molecular docking. Top 9 compounds were observed witihin the range of -8.9 to -7.5 kcal/mol binding score. Five best-fitting compounds in complex with HN receptor were subjected to predict biological activity and further analysis. Top two hits were selected for MD simulations to validate binding modes and structural stability. Finally, upon scrutinization, A1 (ZINC05223166) emerges as potential HN inhibitor to treat NDV, necessitating further validation via clinical trials., 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 this study, biocrude was successfully produced by the hydrothermal liquefaction of municipal solid waste collected from the landfill site of Lahore, the capital of Punjab, Pakistan, boasting a population of 12 million and an annual waste collection of 10 million tons. The hydrothermal liquefaction process was performed at reaction parameters of 350 °C and 165 bars with 15 min of residence time. The solid waste was found to have 78 % dry matter, 22 % moisture contents, 22.2 % ash, 22.69 MJ/kg higher heating value, 52.062 % C, 8.007 % H, 0.764 % N, and 39.164 % O. Non-catalytic process only produced 10.57 % oil, however when using the catalytic process, the biocrude yield improved to 17.61 %, with 22.61 % energy recovery for biocrude and 12.14 % for solids, when using 2 g dose of K 2 CO 3 . The resultant biocrude has a 28.61 MJ/kg higher heating value, having 60.28 % C and 9.28 % H. In contrast, the aqueous phase generated had 4.43 pH, 71.5 g/L TOC, and 1.35 g/L Total Nitrogen. TGA indicated that biocrude contains approximately 80 % of volatile fractions of different fuels. The organic compounds having the six highest peak areas in GC-MS were Ethyl ether 25.74 %, 2-pentanone, 4-hydroxy-4-methyl 9.08 %, 2-propanone, 1,1-dimethoxy 5.62 %, Silane, dimethyl (docosyloxy) butoxy 5.08 %, 1-Hexanol, 2-ethyl 4.53 %, and. Phenol 4.07 %. This work makes the first-ever successful use of indigenous solid waste from a landfill dumping site in Lahore to successfully produce useful biocrude with aims of waste reduction and management, circular economy, and energy recovery., Competing Interests: I have attached the manuscript entitled: Biocrude from Hydrothermal Liquefaction of Indigenous Municipal Solid Waste for Green Energy generation and contribution towards Circular Economy: A Case Study of Urban Pakistan. Imran Naqvi(PhD), Tahir Hussain Seehar(PhD), Muhammad Raashid(PhD), Rab Nawaz(PhD), Zafar Masood(PhD), Sara Mukhtar(MSc), Thamer Abdulhameed Al Johanif(BSc), Anthony Doyle(MSc), Muhammad Nasir Bashir(PhD), Muhammad Mahmood Ali(PhD), M.A. Kalam(PhD), have submitted a research paper for possible publication in Journal of Fuel have no conflict of interest. All the authors who contributed to the work have been mentioned, and they reviewed the manuscript. The work is the author's work and has not been submitted to any journal. Moreover, there is no ethical issue with the manuscript., (© 2024 Published by Elsevier Ltd.)

This paper focuses on the derivation of a new two-parameter discrete probability distribution. The new model is derived by mixing Poisson and Loai distributions and is named "Poisson Loai Distribution". The paper explores various mathematical properties of the new model, introducing a count-regression model based on this distribution. The parameters of the model are estimated using the maximum likelihood estimation method. A comprehensive simulation study is utilized to assess the behavior of derived estimators. The importance of the proposed distribution is confirmed through the analysis of three real datasets. It is found that the suggested distribution has the greatest match when compared to all rival distributions, and it may be a viable alternative for assessing dispersed count data., Competing Interests: The Authors have no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections., 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.)

Waste management poses a major challenge for cities worldwide, with significant environmental, economic, and social impacts. This paper proposes a novel waste management system leveraging recent advances in the Internet of Things (IoT), algorithms, and cloud analytics to enable more efficient, sustainable, and eco-friendly waste collection and processing in smart cities. An ultrasonic sensor prototype is tailored for reliable fill-level monitoring. A LoRaWAN and cellular network architecture provides city-wide connectivity. A cloud platform handles sensor data storage, processing, and analytics. Dynamic route optimization algorithms minimize time, distance, and fuel use based on real-time bin data. Extensive pilot studies in 10 different locations across Lahore, Pakistan, validated the system, processing over 200 million data points. The results showed a 32% improvement in route efficiency, a 29% decrease in fuel consumption and emissions, a 33% increase in waste processing throughput, and 18% vehicle maintenance savings versus conventional practices. This demonstrates quantifiable benefits across operational, economic, and sustainability dimensions. The proposed IoT-enabled waste management system represents a significant advancement towards sustainable and ecologically responsible waste practices in smart cities worldwide. This research provides a replicable model for holistic smart city solutions integrating sensing, algorithms, and analytics to transition civic operations towards data-driven, efficient paradigms. It represents a significant advancement in sustainable waste practices for smart cities worldwide. Further work could apply emerging technologies like automation and artificial intelligence to create waste management 3.0., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Addas 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.)

In a variety of industries, including transportation, agriculture, and manufacturing, diesel engines are often employed. Due of rising prices and environmental concerns, researchers examined whether biodiesels might replace diesel. The current study looks into American Saffron Oil's feasibility as a feedstock for biodiesel production. The transesterification technique is used to extract American saffron oil methyl este(ASOME), which is then examined for its physical and chemical properties in accordance with ASTM standards. Diesel fuel and American Saffron Oil methyl ester are mixed on a volume basis to create a variety of fuel blends, including B20, B40, and B60. The test results showed that the 20 % ASOME mix had better performance and reduced emissions. Also, utilizing DIESEL-RK simulation software, diesel engine tests are conducted for the B20, B40, and B60 under identical operating circumstances. Moreover, diesel engine testing for the B20, B40, and B60 are carried out using DIESEL-RK simulation software under comparable operating circumstances. Results of simulation software tests show improved engine performance and reduced pollutants. When experimental data is compared to DIESEL-RK modeling software, it is found that brake thermal efficiency increased by 5.7 % and emissions of hydrocarbon and carbon monoxide decreased by 2.5 % and 14.3 %, respectively., 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. Published by Elsevier Ltd.)

Background: Gynecological issues and sexually transmitted infections (STIs) pose significant challenges to women's health, particularly in developing nations. These challenges are exacerbated by limited access to modern reproductive healthcare facilities, economic constraints, and entrenched cultural norms. Consequently, most of the Pakistani population relies on traditional ethno-medicinal healthcare systems. This preference stems from the ease of access, affordability, widespread availability, and inherent trust placed in these alternative healthcare methods., Aim/objective: The inquiry aimed to report details on the application of conventional uses of plants in the health field in rural areas that could contribute to advancing the natural discovery of drugs. The objective of this analysis is to provide researchers with information on conventional and empirical knowledge of plant species concerning women's diseases., Methodology: Information on the common use of medicinal plants in treating women's diseases was gathered from electronic databases. As a keyword for the quest, ethnobotany, and ethnopharmacology were used together with gynecological complications., Result: The work of the current analysis has revealed that 217 plant species belonging to 89 families have been used in Pakistan's rural communities. The majority of plant species belong to the Apiaceae family, followed by the Asteraceae, Fabaceae, Solanaceae, Rosaceae, Lamiaceae, and other families. The biological interpretation of plants used in rural communities of Pakistan revealed that herbs and trees are the dominant forms with 58 % and 23 % respectively while shrubs and sub-shrubs with a low percentage of 17 % and 2 %. In natural preparation, leaves 29 %, flowers 22 %, seeds 14 %, fruits 14 %, roots 13 %, bark 7 %, and stems 5 % were the most used parts respectively and aerial parts, dried pericarp, bulb, bud, berry, latex, wood, rhizome, husk, fruit coat, oil, resins, twigs, and shoot were also used in minimum percentage. A multitude of plant species have found extensive application in the management of diverse women's health issues. These encompass concerns such as fatigue, mood fluctuations attributed to menstrual problems, gonorrhea, complications related to pregnancy, cravings for specific foods, throbbing breast pain, abdominal and pelvic cramps, excessive vaginal discharge, mastitis, irritability, abortion-related matters, headaches, uterine hemorrhage, Menorrhagia, Amenorrhea, Menopause, Vomiting Abortion, infertility and lactation challenges, as well as the regulation of lochia flow., Conclusion: This review provides remarkable information about the use of medicinal plants against women's diseases in the rural communities of Pakistan. It opens the gateway for the discovery of natural drug development., 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.)

The rapid improvement of artificial intelligence (AI) in the educational domain has opened new possibilities for enhancing the learning experiences for students. This research discusses the critical need for personalized education in higher education by integrating deep learning (DL) techniques to create customized learning pathways for students. This research intends to bridge the gap between constant educational content and dynamic student needs. This research presents an AI-driven adaptive learning platform implemented across four different courses and 300 students at a university in Faisalabad-Pakistan. A controlled experiment compares student outcomes between those using the AI platform and those undergoing traditional instruction. Quantitative results demonstrate a 25 % improvement in grades, test scores, and engagement for the AI group, with a statistical significance of a p-value of 0.00045. Qualitative feedback highlights enhanced experiences attributed to personalized pathways. The DL analysis of student performance data highlights key parameters, including enhanced learning outcomes and engagement metrices over time. Surveys reveal increased satisfaction compared to one-size-fits-all content. Unlike prior AI research lacking rigorous validation, our methodology and significant results deliver a concrete framework for institutions to implement personalized, AI-driven education at scale. This data-driven approach builds on previous attempts by tying adaptations to actual student needs, yielding measurable improvements in key outcomes. Overall, this work empirically validates that AI platforms leveraging robust analytics to provide customized and adaptive learning can significantly enhance student academic performance, engagement, and satisfaction compared to traditional approaches. These findings have insightful consequences for the future of higher education. The research contributes to the growing demand for AI in education research and provides a practical framework for institutions seeking to implement more adaptive and student-centric teaching methodologies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Abdullah Addas reports financial support was provided by 10.13039/100009392Prince Sattam bin Abdulaziz University. 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., (© 2024 The Authors. Published by Elsevier Ltd.)

This study investigates the impact of public-private partnerships investment in energy and FDI on environmental quality in global investment countries during 1995-2018. Economic growth, technological innovations and consumption of clean energy are also considered as additional determinants of environmental quality. The study applied advanced panel econometric models. Our empirical results affirm the evidence of a long-run association between environmental quality and its determinants. Specifically, economic growth as well as clean energy use improves quality of environment by lowering carbon emissions. Public-private partnerships investment in energy, FDI and technological innovations decrease carbon emissions. Energy consumption (generated from fossil fuel) increases carbon emissions. Heterogeneous causality evidence indicates the presence of a unidirectional causality relation from carbon emissions to public-private partnerships investment in energy and a feedback causality occurs between consumption of clean energy and CO 2 emissions. This empirical evidence provides new insights for both policymakers and governments to support public-private partnership investments in energy for the improvement of quality of environment in global investment countries., 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.)

One of the most prevalent ailments is kidney disease. Effective therapies for chronic renal disease are hard to come by. As a result, there is significant clinical and social interest to predict and develop novel compounds to treat renal disorders. So, specific natural products have been employed in this study because they have protective effects against kidney diseases. When taken orally, natural products can help protect against or lessen the severity of the kidney damage caused by high fructose intake, a high-fat diet, and both Type I and Type 2 diabetes. Reduced podocyte injury, a contributor to albuminuria in diabetic nephropathy, reduces renal endothelial barrier function disruption due to hyperglycemia, as well as urinary microalbumin excretion and glomerular hyperfiltration. Multiple natural products have been shown to protect the kidneys from nephrotoxic chemicals such as LPS, gentamycin, alcohol, nicotine, lead, and cadmium, all of which can persuade acute kidney injury (AKI) or chronic kidney disease (CKD). Natural compounds inhibit regulatory enzymes for controlling inflammation-related diseases. For this, use computational methods such as drug design to identify novel flavonoid compounds against kidney diseases. Drug design via computational methods gaining admiration as a swift and effective technique to identify lead compounds in a shorter time at a low cost. In this in-silico study, we screened The Natural Product Atlas based on a structure-based pharmacophore query. Top hits were analyzed for ADMET analysis followed by molecular docking and docking validation. Finally, the lead compound was simulated for a period of 200 ns and trajectories were studied for stability. We found that NPA024823 showed promising binding and stability with the AIM2. This research work aims to predict novel anti-inflammatory compounds against kidney diseases to inhibit kidney inflammasome by targeting the AIM2 protein. So, in initial preclinical research, there will be lower failure rates that demonstrate safety profiles against predicted compounds.Communicated by Ramaswamy H. Sarma.

Background and Aim: As the spleen plays a significant role in immunity, the aim was to investigate the associations of different body composition markers derived from various sources with spleen volume in a general population sample., Materials and Methods: Cross-sectional data of 1095 individuals (570 women; 52%) aged between 30 and 90 years were collected in the Study of Health in Pomerania (SHIP-START-2). We measured spleen volume by magnetic resonance imaging (MRI).Body composition markers were derived from classic anthropometry, bioelectrical impedance analysis, including absolute fat mass (FM) and fat-free mass (FFM), as well as from MRI, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat content. Sex-stratified-adjusted linear regression models were used to analyze the associations of body composition markers with spleen volumes., Results: We observed positive associations of body mass index, body weight, waist circumference, hip circumference, waist-to-height ratio, absolute FM, absolute FFM, and VAT and SAT with spleen volume in men and women. An 8.12 kg higher absolute FFM was associated with a 38.4 mL (95% confidence interval [CI]: 26.7-50.1) higher spleen volume in men and a 5.21 kg higher absolute FFM with a 42.6 mL (95% CI: 26.2-59.0) higher spleen volume in women., Conclusion: Our findings indicate that obesity-related body composition markers and FFM are associated with a higher spleen volume. Particularly, higher absolute FFM showed a strong association with a larger spleen volume in both men and women. Further studies are warranted to understand the clinical significance of body composition markers on large spleen volume., Competing Interests: The authors report no conflicts of interest., (© 2024 The Author(s). Published by Upsala Medical Society.)

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r2 = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters., Competing Interests: All authors declare that they do not have a conflict of interest relating to conduct of the study or publication of this manuscript., (Copyright: © 2024 Batool 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.)

Evaluating educational climate (EC) is imperative for ensuring postgraduate trainees' competencies and quality in residency training programs. This study assessed the EC experiences of pathology postgraduate residents (PGRs) during their postgraduate training in pathology residency programs-a cross-sectional study design assigned EC scores in the pathology residency program at a prestigious institution in Islamabad, which were measured using the Dutch Residency Educational Climate Test (D-RECT) questionnaire. Scores from the D-RECT were employed to conduct descriptive statistics and comparison of means across groups to evaluate EC scores by years of training and compared to assess where the differences were located. Among FCPS-II pathology residents, most of whom were females (94.4%), the mean age was 28.11±2.91 years. A mean positive score was observed among all pathology residents (M≥3.6) for all D-RECT subscales except for the feedback subscale: the average score for feedback was below the average mean score of 3.6 (M = 3.19). A significant difference p = 0.016 was observed in EC scores across different groups through the Analysis of Variances (ANOVA) test. The most significant difference was between less than two and greater than two groups p = 0.027, followed by the difference between equal to two groups and greater than two groups p = 0.052. Overall, positive scores for EC in the pathology residency program were observed. Thus, targeted interventions are needed to increase feedback scores and address observed differences in EC scores by years of training., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ali 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: Diabetes increases preventative sickness and costs healthcare and productivity. Type 2 diabetes and macrovascular disease consequences cause most diabetes-related costs. Type 2 diabetes greatly costs healthcare institutions, reducing economic productivity and efficiency. This cost of illness (COI) analysis examines the direct and indirect costs of treating and managing type 1 and type 2 diabetes mellitus., Methodology: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane, PubMed, Embase, CINAHL, Scopus, Medline Plus, and CENTRAL were searched for relevant articles on type 1 and type 2 diabetes illness costs. The inquiry returned 873 2011-2023 academic articles. The study included 42 papers after an abstract evaluation of 547 papers., Results: Most articles originated in Asia and Europe, primarily on type 2 diabetes. The annual cost per patient ranged from USD87 to USD9,581. Prevalence-based cost estimates ranged from less than USD470 to more than USD3475, whereas annual pharmaceutical prices ranged from USD40 to more than USD450, with insulin exhibiting the greatest disparity. Care for complications was generally costly, although costs varied significantly by country and problem type., Discussion: This study revealed substantial heterogeneity in diabetes treatment costs; some could be reduced by improving data collection, analysis, and reporting procedures. Diabetes is an expensive disease to treat in low- and middle-income countries, and attaining Universal Health Coverage should be a priority for the global health community., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The secret keys produced by current image cryptosystems, which rely on chaotic sequences, exhibit a direct correlation with the size of the image. As the image dimensions expand, the generation of extensive chaotic sequences in the encryption and decryption procedures becomes more computationally intensive. Secondly, a common problem in existing image encryption schemes is the compromise between privacy and efficiency. Some existing lightweight schemes reveal patterns in encrypted images, while others impose heavy computational burdens during encryption/decryption due to the need for large chaotic sequences. In this study, we introduce a lightweight image encryption scheme that involves partitioning the image into uniformly sized tiles and generating a chaotic sequence accordingly. This approach diminishes the necessity to create extensive chaotic sequences equal to the tile size, which is significantly smaller than the original image. As a result, it alleviates the processing burden associated with generating sequences equivalent to the original image size. The results confirm that our proposed scheme is lightweight and secure compared to the latest state-of-the-art image encryption schemes. Additionally, sensitivity analysis demonstrates that the proposed image encryption technique, with a UACI value of 33.48 and NPRC value of 99.96, affirms its resistance to differential attacks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Khan 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.)

This study aimed to identify efficient Trichoderma isolate(s) for the management of Fusarium wilt in peas. Four different pea germplasms (Sarsabz, Pea-09, Meteor and Supreme) were evaluated for resistance against Fusarium oxysporum in pot assay. Resistant germplasm exhibits a varying range of disease severity (23%) and percent disease index (21%), whereas susceptible and highly susceptible germplasm exhibit maximum disease severity (44-79%) and percent disease index (47-82%). The susceptible germplasm Meteor was selected for in vivo experiment. Five different Trichoderma spp. ( Trichoderma koningii , T. hamatum , T. longibrachiatum , T. viride , and T. harzianum ) were screened for the production of hydrolytic extracellular enzymes under in vitro . In-vitro biocontrol potential of Trichoderma spp. was assayed by percentage inhibition of dry mass of Fusarium oxysporum pisi (FOP) with Trichoderma spp. metabolite filtrate concentrations. Maximum growth inhibition was observed by T. harzianum (50-89%). T. harzianum metabolites in filtrate conc. (40%, 50%, and 60%) exhibited maximum reduction in biomass and were thus used for in vivo management of the disease. The pot experiment for in-vivo management also confirmed the maximum inhibition of FOP by T. harzianum metabolites filtrate at 60% by reducing disease parameters and enhancing growth, yield, and physiochemical and stress markers. Trichoderma strains led to an increase in chlorophyll and carotenoids (34-26%), Total phenolic 55%, Total protein content 60%, Total Flavonoid content 36%, and the increasing order of enzyme activities were as follows: CAT > POX > PPO > PAL in all treatments. These strains demonstrate excellent bio-control of Fusarium wilt in pea via induction of defense-related enzymes. The present work will help use Trichoderma species in disease management programme as an effective biocontrol agent against plant pathogens., 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. Published by Elsevier Ltd.)

Manual ground searches and cadaver dogs are traditional methods for locating remains, but they can be time- and resource-intensive, resulting in the decomposition of bodies and delay in victim identification. Therefore, thermal imaging has been proposed as a potentially useful tool for detecting remains based on their temperature. This study investigated the potential of a novel search technique of thermal drones to detect surface remains through the detection of maggot mass temperatures. Two trials were carried out at Selangor, Malaysia, each utilizing 12 healthy male Oryctolagus cuniculus European white rabbits and DJI Matrice 300 RTK drone China, equipped with a thermal camera; Zenmuse H20T to record the thermal imaging footage of the carcasses at various heights (15, 30, 60-100 m) for 14 days for each trial. Our results demonstrated that the larval masses and corresponding heat emissions were at their largest during the active decay stage; therefore, all the carcasses were observable in thermal images on day 5 and remained until day 7. Statistical analyses showed that (1) no statistically significant differences in thermal images between clothed and unclothed subjects (p > 0.05); (2) 15 m above ground level was proven to be the optimal height, as it showed the greatest contrast between the carcass heat signature and the background (p < 0.005). Our data suggested the potential window of detection of thermal signatures was detectable up to 7 days post-deposition. This could be an important guideline for the search and recovery teams for operational implementation in this tropical region., (© 2024 The Authors. Journal of Forensic Sciences published by Wiley Periodicals LLC on behalf of American Academy of Forensic Sciences.)

Due to damage to the network of nerves that regulate the muscles and feeling in the shoulder, arm, and forearm, brachial plexus injuries (BPIs) are known to significantly reduce the function and quality of life of affected persons. According to the World Health Organization (WHO), a considerable share of global disability-adjusted life years (DALYs) is attributable to upper limb injuries, including BPIs. Telehealth can improve access concerns for patients with BPIs, particularly in lower-middle-income nations. This study used deep reinforcement learning (DRL)-assisted telepresence robots, specifically the deep deterministic policy gradient (DDPG) algorithm, to provide in-home elbow rehabilitation with elbow flexion exercises for BPI patients. The telepresence robots were used for a six-month deployment period, and DDPG drove the DRL architecture to maximize patient-centric exercises with its robotic arm. Compared to conventional rehabilitation techniques, patients demonstrated an average increase of 4.7% in force exertion and a 5.2% improvement in range of motion (ROM) with the assistance of the telepresence robot arm. According to the findings of this study, telepresence robots are a valuable and practical method for BPI patients' at-home rehabilitation. This technology paves the way for further research and development in telerehabilitation and can be crucial in addressing broader physical rehabilitation challenges.

Background: Radiation exposure is a significant hazard associated with invasive Cardiology, with most studies based on primary operator exposure. This prospective, observational study aimed to find out over lead radiation exposure as effective dose acquired by non-physician staff comprising scrub technicians and rotating staff in the cath laboratory. Effective dose (ED) measured per procedure via Raysafe i2®dosimeter badges worn by both rotating staff and scrub technicians over lead aprons along with dose area product (DAP), fluoroscopy time (FT) and procedure time (PT) in minutes was collected prospectively over forty-six invasive Cardiology procedures., Results: This study shows that rotating staff acquire higher ED in comparison with their scrub technician colleagues in diagnostic, interventional and electrophysiology cases. However, a statistically significant difference in radiation exposure of both staff groups was demonstrated in diagnostic and interventional Cardiology procedures, with p values of 0.04 and 0.01, respectively., Conclusions: These findings highlight occupational role and mobility around fluoroscopic sources as major factors in radiation exposure, which should be addressed within current radiation protection practices., (© 2024. The Author(s).)

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

Physicochemical and phytochemical assessment of leaf mustard (Brassica juncea L.) grown in different agroclimatic conditions is essential to highlight their compositional variability and evaluate the most suitable bunch of agroclimatic and agronomic practices. B. juncea is one of the important leafy vegetables that serve as source of vitamin A and C and iron, and plenty of antioxidants. This in situ research was executed to assess the quality variability of B. juncea grown in different agroecosystems. Leaves' samples of B. juncea were procured from 15 farmers' fields exhibiting different agroclimatic conditions i.e., elevation, nutrient management, temperature, irrigation, and tillage practices. Leaves' samples were subjected to physicochemical and phytochemical analysis, i.e., moisture, pH, TSS, ascorbic acid, carotenoids, phenolics, flavonoids, and antioxidant potential. In the leaves' samples of B. juncea, the target properties were found to vary significantly (P ≤ 0.05) in different agroclimatic conditions. The moisture content, ascorbic acid, phenolic content, carotenoids, and antioxidants were found in the range of 62.7-79.3%, 74-91 mg/100 g, 49.2-49.2 mg GAE/100 g, 436.3-480 mg β carotene/100 g, 32.7-46.67%, respectively. This study elaborates the significant variation of physicochemical and phytochemical attributes of B. juncea due to the prevailing agroclimatic conditions. This necessitates the appropriate choice of B. juncea concerning its composition and ecological conditions of its cultivation in the prospective health benefits., (© 2024. The Author(s).)

Rose bengal (RB) solutions coupled with a green laser have proven to be efficient in clearing resilient nail infections caused by Trichophyton rubrum in a human pilot study and in extensive in vitro experiments. Nonetheless, the RB solution can become diluted or dispersed over the tissue and prevented from penetrating the nail plate to reach the subungual area where fungal infection proliferates. Nanoparticles carrying RB can mitigate the problem of dilution and are reported to effectively penetrate through the nail. For this reason, we have synthesized RB-encapsulated chitosan nanoparticles with a peak distribution size of ~200 nm and high reactive oxygen species (ROS) production. The RB-encapsulated chitosan nanoparticles aPDT were shown to kill more than 99% of T. rubrum, T. mentagrophytes, and T. interdigitale spores, which are the common clinically relevant pathogens in onychomycosis. These nanoparticles are not cytotoxic against human fibroblasts, which promotes their safe application in clinical translation., (© 2023 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)

Objective: To evaluate the clinical results of intravascular ultrasound (IVUS)-guided intervention for calcified coronary artery lesions., Study Design: Observational study. Place and Duration of the Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from January 2013 to January 2020., Methodology: A cohort of 134 consecutive patients who underwent intravascular ultrasonography-guided assessment of coronary arteries were included. Patients were divided into two groups: those with coronary artery calcification (CAC, n=77) and those without (non-CAC, n=57). The two groups were compared for their clinical characteristics, management, in-hospital events, follow-up, and major adverse cardiovascular events (MACEs)., Results: The mean follow-up duration was 40.3 ± 30.1 months. Most of the patients were male (n=97, 72.3%), and the mean age was 63.1 ± 12.9 years. In the CAC group, age was the most common risk factor, followed by dyslipidaemia (n=68, 88%), hypertension (n=64, 83%), and Diabetes mellitus (n=44, 57%). CAC group patients were more commonly presented with acute coronary syndrome (n=59, 76.6%), had prior PCI (n=40, 52%), had more LM disease (n=34, 44%, p=0.005), and a significant number of prior stent-ISR (n=27, 35%, p=0.024). Those who had CAC had higher MACE., Conclusion: Patients with CAC had more co-morbidities and commonly presented with acute coronary syndrome. MACEs frequency was recorded higher in the CAC group although the results were not statistically significant., Key Words: Coronary artery calcification, Intravascular imaging, Coronary artery disease, Target vessel revascularisation, Percutaneous coronary intervention.

Cardiovascular disorders are the world's major cause of death nowadays. To treat cardiovascular diseases especially coronary artery diseases and hypertension, researchers found potential ROCK2 (Rho-associated coiled-coil-containing protein kinase 2) target due to its substantial role in NO-cGMP and RhoA/ROCK pathway. Available drugs for ROCK2 are less effective and some of them depict side effects. Therefore, a set of novel compounds were screened that can potentially inhibit the activity of ROCK2 and help to treat cardiovascular diseases by employing In-silico techniques. In this study, we undertook ligand based virtual screening of 50 million compound's library, to that purpose shape and features (contain functional groups) based pharmacophore query was modelled and validated by Area Under Curve graph (AUC). 2000 best hits were screened for Lipinski's rule of 5 compliance. Subsequently, these selected compounds were docked into the binding site of ROCK2 to gain insights into the interactions between hit compounds and the target protein. Based on binding affinity and RMSD scores, a final cohort of 15 compounds were chosen which were further refined by pharmacokinetics, ADMET and bioactivity scores. 2 potential hits were screened using density functional theory, revealing remarkable biological and chemical activity. Potential inhibitors (F847-0007 and 9543495) underwent rigorous examination through MD Simulations and MMGBSA analysis, elucidating their stability and strong binding affinities. Results of current study unveil the potential of identified novel hits as promising lead compounds for ROCK2 associated with cardiovascular diseases. These findings will further investigate via In-vitro and In-vivo studies to develop novel druglike molecules against ROCK2., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ali 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.)

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain., Objective: To determine whether vitamin C improves outcomes for patients with COVID-19., Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents., Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses)., Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility., Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy., Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival., Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

The nikkomycins S z /So z are a class of locked nucleoside antibiotics that share a common [5,6] trans -bicyclic core. Herein we present an efficient synthesis of these nikkomycins from diene, using neighboring group participation N -glycosylation and stereoselective oxidation state installation. This synthetic strategy overcomes several challenges due to the poor redox tolerance of the uracil base, the high strain of the trans -fused furanopyran C8 monosaccharides, and the acid-sensitive glycosidic bond when dealing with the deoxynucleotide natural product nikkomycin S z .

Null.

A number of multidisciplinary methods have piqued the interest of researchers as means to accelerate and lower the cost of medication creation. The goal of this research was to find target proteins and then select a lead drug against SARS-CoV-2. The three-dimensional structure is taken from the RCSB PDB using its specific PDB ID 6lu7. Virtual screening based on pharmacophores is performed using Molecular Operating Environment software. We looked for a potent inhibitor in the FDA-approved database. For docking, AutoDock Vina uses Pyrx. The compound-target protein binding interactions were tested using BIOVIA Discovery Studio. The stability of protein and inhibitor complexes in a physiological setting was investigated using Desmond's Molecular Dynamics Simulation (MD simulation). According to our findings, we repurpose the FDA-approved drugs ZINC000169677008 and ZINC000169289767, which inhibit the activity of the virus's main protease (6lu7). The scientific community will gain from this finding, which might create new medicine. The novel repurposed chemicals were promising inhibitors with increased efficacy and fewer side effects.Communicated by Ramaswamy H. Sarma.

The global burden of dengue infections has increased dramatically. Early diagnosis of dengue infection is critical to proper medical management to avoid further complications in patients. This study was geared to assess the severity of dengue infections based on clinical and hematological examinations. A cross-sectional study was conducted among febrile patients with dengue infection in a teaching hospital in Pakistan. Blood samples were investigated for dengue-specific antibodies (IgM and IgG) and the nonstructural 1 antigen. The clinical findings of each subject were noted to assess the severity of the infection. Tests for hematological parameters were performed. Of 130 patients with confirmed dengue infection, 23 had severe and 107 had nonsevere dengue. Patients with severe dengue experienced mucosal bleeding (71.4%), fluid accumulation (57.1%), shock (35.7%), and gastrointestinal bleeding (28.6%). The most significant hematological findings among severe and nonsevere patients with dengue infection were thrombocytopenia, leukopenia, and a raised hematocrit level (P < 0.001). Patients with severe dengue infection showed marked thrombocytopenia, with a mean platelet count of 49.96 × 109 platelets/L. The clinical presentation of patients with dengue infection along with hematological markers are the most important clues for the diagnosis of, prognosis of, and therapy for dengue infection. Thrombocytopenia, leukopenia, and raised hematocrit levels were the most significant hematological parameters when assessing the severity of dengue infection.

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94-98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 μg/mL RB-nanoparticles, fluence ~126 J/cm 2 , and irradiance ~0.21 W/cm 2 ). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications.

Geraniol (GER) is a plant-derived acyclic isoprenoid monoterpene that has displayed anti-inflammatory effects in numerous in vivo and in vitro models. This study was therefore designed to evaluate the antiarthritic potential of GER in complete Freund's adjuvant (CFA)-induced inflammatory arthritis (IA) model in rats. IA was induced by intraplantar injection of CFA (0.1 mL), and a week after CFA administration, rats were treated with various doses of methotrexate (MTX; 1 mg/kg) or GER (25, 50, and 100 mg/kg). Treatments were given on every alternate day, and animals were sacrificed on the 35th day. Paw volume, histopathological, hematological, radiographic, and qPCR analyses were performed to analyze the severity of the disease. GER significantly reduced paw edema after 35 days of treatment, and these results were comparable to the MTX-treated group. GER-treated animals displayed a perfect joint structure with minimal inflammation and no signs of cartilage or bone damage. Moreover, GER restored red blood cell and hemoglobin levels, normalized erythrocyte sedimentation rate, platelet, and c-reactive protein values, and also attenuated the levels of rheumatoid factor. RT-qPCR analysis demonstrated that GER decreased mRNA expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta. GER also down-regulated the transcript levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1, prostaglandin D2 synthase, and interstitial collagenase (MMP-1). Molecular docking of GER with COX-2, TNF-α, and MMP-1 also revealed that the antiarthritic effects of GER could be due to its direct interactions with these mediators. Based on our findings, it is conceivable that the antiarthritic effects of GER could be attributed to downregulation of pro-inflammatory mediators and protease like MMP-1., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

We report the proteomic profile of Epidermal Mucus (EM) from Labeo rohita and identified the differentially abundant proteins (DAPs) against Aeromonas hydrophila infection through label-free liquid chromatography-mass spectrometry (LC-MS/MS). Using discovery-based proteomics, a total of 2039 proteins were quantified in nontreated group and 1,328 proteins in the treated group, of which 114 were identified as DAPs in both the groups. Of the 114 DAPs, 68 proteins were upregulated and 46 proteins were downregulated in the treated group compared to nontreated group. Functional annotations of these DAPs shows their association with metabolism, cellular process, molecular process, cytoskeletal, stress, and particularly immune system. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Fisher's exact test between the two groups shows that most of the proteins were immune-related, which were significantly associated with the proteasome, phagosome, and Salmonella infection pathways. Overall, this study shows a basic and primary way for further functional research of the involvement of vitellogenin 2, alpha-2-macroglobulin-like protein, toll-like receptors (TLR-13), calpain, keratin-like proteins, and heat shock proteins against bacterial infection. Nonetheless, this first-ever comprehensive report of a proteomic sketch of EM from L. rohita after A. hydrophila infection provides systematic protein information to broadly understand the biological role of fish EM against bacterial infection., 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., (© 2023 The Author(s).)

In the past two decades, there have been three coronavirus outbreaks that have caused significant economic and health crises. Biologists predict that more coronaviruses may emerge in the near future. Therefore, it is crucial to develop preventive vaccines that can effectively combat multiple coronaviruses. In this study, we employed computational approaches to analyze genetically related coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, focusing on the spike glycoprotein as a potential vaccine candidate. By predicting common epitopes, we identified the top epitopes and combined them to create a multi-epitope candidate vaccine. The overall quality of the candidate vaccine was validated through in silico analyses, confirming its antigenicity, immunogenicity, and stability. In silico docking and simulation studies suggested a stable interaction between the multi-epitope candidate vaccine and human toll-like receptor 2 (TLR2). In silico codon optimization and cloning were used to further explore the successful expression of the designed candidate vaccine in a prokaryotic expression system. Based on computational analysis, the designed candidate vaccine was found to be stable and non-allergenic in the human body. The efficiency of the multi-epitope vaccine in triggering effective cellular and humoral immune responses was assessed through immune stimulation, demonstrating that the designed candidate vaccine can elicit specific immune responses against multiple coronaviruses. Therefore, it holds promise as a potential candidate vaccine against existing and future coronaviruses.

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Autoimmune diabetes, well-known as type 1 insulin-dependent diabetic mellitus (T1D). T1D is a prolonged condition marked by an inadequate supply of insulin. The lack is brought on by pancreatic cell death and results in hyperglycemia. The immune system, genetic predisposition, and environmental variables are just a few of the many elements that contribute significantly to the pathogenicity of T1D disease. In this study, we test flavonoids against Coxsackie virus protein to cope the type 1 diabetes. After protein target identification we perform molecular docking of flavonoids and selected target (1z8r). then performed the ADMET analysis and select the top compound the base of the docking score and the ADMET test analysis. Following that molecular dynamics simulation was performed up to 300 ns. Root means square deviation, root mean square fluctuation, secondary structure elements, and protein-ligand contacts were calculated as post-analysis of simulation. We further check the binding of the ligand with protein by performing MM-GBSA every 10 ns. Lead compound CID&#95;5280445 was chosen as a possible medication based on analysis. The substance is non-toxic, meets the ADMET and BBB likeness requirements, and has the best interaction energy. This work will assist researchers in developing medicine and testing it as a treatment for Diabetes Mellitus Type 1 brought on by Coxsackie B4 viruses by giving them an understanding of chemicals against these viruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ullah 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.)

Diabetes mellitus (DM) is the most prevalent endocrine disorder. Numerous individual herbs possess anti-diabetic activity. The seeds of Hordeum vulgare , Elettaria cardamomum and Cicer arietinum are traditionally used to manage DM. The ambition of this work was to formulate the poly-herbal granules (PHGs) comprising of these three functional foods and evaluate their in-vitro antioxidant and antidiabetic potential. The dried seed extracts of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum were used in a ratio of 2.5:1:1 to formulate PHGs by wet granulation method. The ratio of extracts was selected on the basis of traditional phytotherapies popularly used by local Hakeems of Pakistan to achieve glycemic control in diabetic patients resistant to traditional allopathic regime of medicine. The flow properties of developed PHGs were evaluated. The UV-Visible spectroscopic, Fourier Transform Infrared (FTIR) and HPLC-DAD of all seed extracts and PHGs were performed. The in-vitro antioxidant DPPH, FRAP, total antioxidant capacity (TAC) and Nitric Oxide (NO) scavenging assays were carried out on PHGs. The in-vitro antidiabetic activity of PHGs was investigated by alpha-amylase and alpha-glucosidase enzyme inhibition activity. The developed PHGs exhibited excellent flow properties. The UV-Vis spectra of all seed extracts and PHGs demonstrated peak at 278 nm showing the presence of flavonoids and phenols. The FTIR spectra confirmed the existence of fl avonoids, and phenols along with amines in seed extracts as well as PHGs. The HPLC-DAD test revealed the existence of gallic acid, ascorbic acid, Quercetin-3-(caffeoyldiglucoside)-7-glucoside, Rosmarinic acid, delphinidin-3,5-diglucosides, Kaempferol-3-feruloylsophoroside-7-glucoside and Phloroglucinol in PHGs. The PHGs exhibited IC 50 of 51.23, 58.57, 55.41 and 53.13 μg/mL in DPPH assay, FRAP assay, TAC, Nitric oxide scavenging assays respectively. The PHGs also demonstrated IC 50 of 49.97 and 36.16 μg/mL in alpha-amylase and in alpha-glucosidase inhibition assays respectively in dose dependent manner. The developed PHGs exhibited an excellent flow property. These exhibit significant in-vitro antioxidant and antidiabetic profile by virtue of flavonoid and phenolic acid derivatives., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Muhammad Furqan Akhtar serves as Advisory board member of Heliyon Journal., (© 2023 The Authors.)

Camellia sinensis is rich in antioxidants such as polyphenols; Thymus vulgaris contains bioactive compounds (flavonoids, terpenoids, and tannins) and Zanthoxylum armatum is primarily composed of volatile oils, amides, alkaloids, flavonoids, lignan, and coumarin. The antibacterial, antifungal, biofilm inhibition, antioxidant, hemolytic, and thrombolytic activities of Camellia sinensis , Thymus vulgaris , and Zanthoxylum armatum ethanol and methanol extracts at different concentrations (30%, 50%, and 80%) were determined. The antioxidant activity and content were measured as free radical scavenging assay (DPPH), total flavonoid content (TFC), and total phenolic content (TPC). Furthermore, hemolytic and thrombolytic analysis was carried out to determine toxicity. In antimicrobial assays, 80% methanol thyme extract showed highest (15.31 mm) antibacterial activity against Bacillus subtilis , and 80% ethanol green tea extract showed optimal antibacterial activity against Staphylococcus aureus . Ethanol 30% green tea extract resulted in highest (26.61 mm) antifungal activity against Aspergillus niger . The maximum (54.73%) biofilm inhibition was resulted by methanol 50% thyme extract for Escherichia coli . In antioxidant activity and content, methanol 50% green tea extract had highest (80.82%) antioxidant activity, whereas, ethanol 80% green tea extract had maximum (1474.55 mg CE/g DW) TFC and methanol 80% green tea extract had maximum (593.05 mg GAE/g) TPC. In toxicological assays, methanol 30% green tea extract had highest (25.28%) thrombolytic activity, and ethanol 80% tejphal extract had maximum (18.24%) hemolytic activity. This study has highlighted the significant antimicrobial, antioxidant, hemolytic, and thrombolytic activities of Camellia sinensis , Thymus vulgaris , and Zanthoxylum armatum extracts that could be beneficial to treat various diseases (cancer, diabetes, and respiratory diseases) and may be utilized as functional ingredient in the preparation of functional foods and drinks., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background : Hermetia illucens L. have gained popularity in recent years as an environmentally friendly response to both the present and potential future food/feed crisis. The larvae of H. illucens L., or black soldier fly larvae (BSFL), is an alternative solution to tackle the issue of organic waste bioconversion. However, understanding the environmental loads associated with biowaste bioconversion using BSFL to produce dried BSFL is a pivotal point to keep the environment sustainable. This study reported a life cycle assessment (LCA) of the biowaste bioconversion process of BSFL and determined the environment impact analysis to make recommendations for modifications to lessen environmental consequences. Methods : The methodology used is life cycle assessment (LCA), which includes: (a) system boundary determination (gate-to-gate), starting from biowaste production, biowaste bioconversion, prepupae and BSFL frass production. The system boundary of the dried BSFL production is designed for both the processing and production of one cycle of BSFL; (b) life cycle inventory activities carried out at PT Biomagg Sinergi Internasional, Depok, West Java, Indonesia; (c) conducting life cycle impact assessment on five environmental impact categories namely global warming potential (GWP), acidification (AC), terrestrial eutrophication (TE), fossil fuel depletion (FFE), eco-toxicity (ET); and (d) interpretation of the assessment result. The LCA is conducted using openLCA 1.11 software and TRACI 2.1 impact assessment method. Results : The impact values of GWP, AC, TE, FFE, and ET, per 100 kg of BSFL dried production was 6.687 kg CO 2 eq; 0.029 kg SO 2 -eq; 0.092 kg N-eq; 16.732 MJ surplus; 121.231 CTUe. Production of prepupa had the highest hotspots in these emissions, followed dried BSFL production. Conclusions: Efforts to reduce environmental impacts that can be done are by implementing an integrated rearing system using substrate from a single type of known substrate for BSFL and using alternative drying methods for BSFL dried production., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Nugroho RA et al.)

Background: Partial Nephrectomy has been the go-to approach for the treatment of small sized renal tumours for years now. Like any other surgical procedure, it is associated with post-operative complications. The study was aimed at determining the post-operative complications of open partial nephrectomy concerning tumour location., Methods: This descriptive cross-sectional study was done on 45 patients as per inclusion criteria. The patients were managed as per department protocols and were observed for the development of immediate post-operative complications during hospital stays. RESULTS: Post-operative complications were observed in 4 (8.9%) patients and included haemorrhage (n=1; 2.2%) and urine leak (n=3; 6.7%). There was a statistically significant association between post-operative complications of partial nephrectomy and central tumour location (p=0.008, OR=14.52 and LR=5.70) and increased age (p=0.04, LR=5.40 and OR=8.90)., Discussion: Increased age and tumour location may play a significant role in determining the likelihood of post-operative complications in patients who have undergone surgery for renal tumours.