Introduction: Migraine is a highly disabling neurological condition with substantial variability in its clinical presentation. This study aimed to explore the influence of familial transmission of comorbid medical conditions on the phenotype of chronic and episodic migraine. Methods: A total of 500 patients who presented to a private tertiary headache clinic were categorized into episodic and chronic migraine groups based on the International Classification of Headache Disorders-3 criteria. Data on demographics, clinical symptoms, and familial medical history were collected. Statistical analysis included chi-square and independent sample t-tests to evaluate the impact of familial comorbidities on migraine phenotypes. Results: Of the participants, 63% were diagnosed with episodic migraine and 37% with chronic migraine. Significant findings included higher rates of medication overuse (63.31%) and allodynia (58.82%) in patients with chronic migraine. Notably, patients with a maternal history of hypercholesterolemia showed a higher prevalence of chronic migraine (78.6%), whereas those with both parents affected tended to have episodic migraine. Educational levels are inversely correlated with the prevalence of chronic migraine, suggesting a socioeconomic influence on migraine chronification. Discussion: This study highlights significant associations between familial health conditions and migraine phenotypes. The findings suggest that the maternal transmission of comorbidities, particularly hypercholesterolemia, may influence the development of chronic migraine. These results underscore the importance of considering familial medical history in the management and understanding of migraine.

Background: Medication errors often stem from incomplete or incorrect transfer of drug information during reviews. To enhance medication review processes, a collaborative healthcare team, including a pharmacist in the surgical ward, is essential. This study aimed to identify the frequency and the kind of intentional and unintentional discrepancies related to the prescriptions within two surgical wards. Methods: A prospective observational study was conducted among adult patients admitted to two surgical settings. The patients were selected between May 30th and November 30th, 2021. The study followed a three-phase structure: patient selection, medication review to identify discrepancies and DRPs, and the detection of any such issues in the discharge letter. Results: The most frequent types of discrepancies collected were substitutions (60.9%) for the Endocrinological Surgery and omissions for General Surgery (53.4%). In Endocrinological Surgery, 45.9% of cases exhibited class C drug interactions. In General Surgery, class D drug interactions were predominantly observed (54.1%), with 93.3% attributed to drugs carrying an elevated risk of prolonging the QT interval. Conclusions: Frequently, the medication review process is superficially carried out, introducing errors that may adversely affect patient health. This study explores the potential positive impact of involving the clinical pharmacist in identifying and managing discrepancies and DRPs.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

The leaves of Nicotiana glauca (Solanaceae) plant, are known for its major cause of health concern. This study investigated the antioxidant activity and polyphenols composition of aerial parts of N.glauca collected from its wild habitat in Jordan, using Methanol-Conventional (MC) and deep eutectic solvents (DESs) extraction methods in addition to nicotine content determination using UHPLC. The results have shown that the MC extract contains fewer total phenols and flavonoid content than the DES extract at ratio of 90% (0.1194 ±0.009 and 0.311± 0.020 mg/mL equivalent to gallic acid) and (0.01084±0.005 and 0.928 ± 0.09 mg/mL equivalent to rutin), respectively. Moreover, the study showed that the MC extract contains 635.07 ppm nicotine compared to the DES extraction method, which contains 1194.91 ppm. Both the MC and the DES extracts exhibited weak antioxidant activities with the highest was 33%inhibition equivalent to ascorbic acid was found for DES at (90%) ratio. The UHPLC-MS/MS analysis revealed the presence of variations in the detected compounds between the two extraction methods used. This study found that en-vironmentally friendly DES extraction of N. glauca produced higher phenol and flavonoid content than MC method, highlighting green chemistry methods' superior efficiency and environmental benefits for extracting valuable phytoconstituents.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Eosinophils are key therapeutic targets in severe asthma as they accumulate in tissues, resulting in local damage through the release of toxic mediators. Benralizumab is a monoclonal antibody with a direct anti-eosinophilic activity that has proved significant clinical efficacy in patients with severe eosinophilic asthma, and its use in real-life went well beyond what we had expected from the pivotal trials, especially in the reduction of asthma exacerbations and oral steroids usage. Benralizumab induces eosinophil apoptosis due to a mechanism of antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells. Within this review, we will discuss benralizumab pharmacological and pharmacokinetic aspects in the treatment of severe asthma, with an emphasis on the novel immunological effects of benralizumab on NK cells. Overall, these findings account for the clinical efficacy and safety profile of benralizuamb, previously described in patients with an eosinophilic phenotype of the disease.

Background/Objectives: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with the endogenous reactivation of human herpesvirus (HHV)-6 and HHV-7. Classically, the lesions gradually resolve leaving no sequelae. Therefore, the best treatment is reassuring the patient and suggesting a resting period. However, atypical PR cases characterized by extensive, persistent lesions and systemic symptoms may impact the patient’s quality of life, and, therefore, a treatment can be prescribed. There is limited evidence on the comparative effectiveness of pharmacological treatments for PR, therefore we performed a network meta-analysis to compare these interventions. Methods: Overall, 12 randomized control trials (RCTs) were identified. The outcomes were itch resolution and rash improvement. Results were expressed as risk ratio (RR) and 95% confidence interval (CI). We also calculated the relative ranking of the interventions for achieving the aforementioned outcomes as their surface under the cumulative ranking (SUCRA). Results: On network meta-analysis, only oral steroids and the combination of oral steroids+antihistamine resulted significantly superior to the placebo in terms of itch resolution (RR 0.44, CI 0.27-0.72 and RR 0.47, CI 0.22-0.99). Oral steroids resulted as the best treatment (SUCRA 0.90) for itch resolution. In terms of rash improvement, only acyclovir and erythromycin resulted significantly superior to placebo (RR 2.55, CI 1.81-3.58 and RR 1.69, CI 1.23-2.33), and acyclovir outperformed all the other tested interventions. Consequently, acyclovir ranked as the best intervention (SUCRA score 0.92). Conclusions: Acyclovir represents the best option in PR patients with extensive, persistent lesions or systemic symptoms. Steroids and antihistamines seemed the best treatment for itch resolution.

The neuronal etiology of obesity is centered around diet-induced inflammatory state in the arcuate nucleus of the hypothalamus which impairs the functionality of pro-opiomelanocortine neurons (POMCs) responsible for whole-body energy homeostasis and feeding behavior. Intriguingly, systemic salt inducible kinase 2 (SIK2) knockout mouse demonstrated reduced food intake and energy expenditure along with modestly dysregulated metabolic parameters suggesting a causal link between the absence of SIK2 activity in POMCs and the observed phenotype. To test this hypothesis, we conducted a comparative secretomics study from POMC neurons following pharmacologically induced endoplasmic reticulum (ER) stress induction, a hallmark of metabolic inflammation and POMC dysregulation in diet induced obese (DIO) mice. Our data provide significant in vitro evidence for the POMC specific SIK2 activity in controlling the energy metabolism and feeding in DIO mice by regulating the nature of related POMC secretome. Our data also suggests that under physiological stress conditions SIK2 may act as a gatekeeper for the secreted inflammatory factors and signaling molecules critical for cellular survival and energy homeostasis. On the other hand, in the absence of SIK2 gate opens leading to surge of inflammatory cytokines and apoptotic cues concomitant with the dysregulation of POMC neurons.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

Picrasma javanica Blume or also known as Picrasma nepalensis or Picrasma philippinensis is a plant belongs to the Simaroubaceae family, which is known for its secondary metabolites namely quassinoids with various pharmacological properties including antitumor, antimalarial and antiviral. The plant traditionally used as medicine for different diseases in Myanmar, Thailand and Indonesia. The purpose of this study is to discern the phytochemical constituents and pharmacological activities of Picrasma javanica. The background, phytochemical constituents and pharmacological benefits of Picrasma javanica were reviewed and supported from previous studies, including in vivo and in vitro studies. The literature used in the review comprises of published books, journals, reviews and articles published from the year of 1969 to 2018, which are available in ScienceDirect, PubMed, Scopus and GoogleScholar. Chemical structures presented in this paper are either drawn with ACD/ChemSketch. Picrasma javanica possesses several phytochemical constituents, including quassinoids, alkaloids and triterpenoids. Compounds of the plant were isolated and studied for their pharmacological activities such as antimalarial, antiproliferative, antiviral, antimicrobial and membrane stabilising activity. Most importantly, these studies showed that the key players for the pharmacological benefits are quassinoids and alkaloids present in the plant.Picrasma javanica indeed has therapeutic potentials which may be beneficial for people. However, further extensive studies must be done on the plant as the detailed information on its pharmacological activities are still lacking.

Migraine is a debilitating neurological condition affecting millions of people worldwide. Until few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications and discovered by serendipity to be effective in migraine prevention although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed to identify novel putative targets as calcitonin gene-related peptide (CGRP). Nevertheless, despite the revolution brought by CGRP monoclonal antibodies and gepants, a significant percentage of patients still remains burdened by an unsatisfactory response suggesting that other pathways may play a critical role with an extent of involvement varying among different migraine patients. Specifically, neuropeptides of the CGRP family as adrenomedullin and amylin, molecules of the secretin family as pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP), receptors as transient receptor potential (TRP) channels, intracellular downstream determinants as potassium channels but also the opioid system and the purinergic pathway have been suggested to be involved in migraine pathophysiology. The present review provides an overview of these pathways highlighting, based on preclinical and clinical evidences as well as provocative studies, their potential role as future targets for migraine preventive treatment.

Since ancient times, various scientists and doctors have utilized different herbs to heal diseases. Due to the rise in drug resistance and the negative effects of chemosynthetic drugs, researchers and the general public around the world have become more interested in medicinal herbs and plant metabolites/extracts. This is due to its non-toxicity and several health benefits when used to treat diseases in clinical and medical settings. Ocimum basilicum is one such plant, possessing a wide range of bioactive phytochemicals including alkaloids, phenolics, flavonoids, tannins, saponins, reducing sugars, cardiac glycosides, steroids and glycosides, as well as complex pharmacological activities including anti-inflammatory, antifungal, antibacterial, antioxidant, wound healing and antiviral properties. The results of many studies on Ocimum basilicum plant extracts are collected and presented in this review. The plant extracts have an excellent potential to be used as medicinal raw materials and exhibit an extensive variety of therapeutic capacities, including antibacterial, antioxidant, wound healing, anti-inflammatory, antifungal, and antiviral properties.

Plant secondary metabolites are organic compounds (alkaloids, flavonoids, phenolics, tannins, anthraquinones, saponins, steroids, lignins, terpenes) produced by plant for self-defense during growth and development in order to protect them from harmful agents. As population is increasing and quality of life is reducing couple with outbreak of some diseases that are posing threat on the economy, a lot of medicinal plants have attracted interest of researchers because of the usefulness of these metabolites in pharmaceuticals, food and cosmetic industries. In this review, the pharmacological activities of some medicinal plants that are rich in secondary metabolites were studied, means of identifying and quantifying using spectrophotometry and chromatography techniques were also discussed. However, this will assist to reduce the uses and dependent on the synthetic drug and the onset of the age related diseases.

In 1789, the Annonaceae family was cataloged by de Jussieu. It encompasses tropical and subtropical plants which are widespread in distribution across various continents such as Asia, South and Central America, Australia and Africa. The genus of Annona is one of the 120 genera of the Annonaceae family and contains more than 119 species of trees and shrubs. The majority of these species are found in tropical America with more than 105 species (26 of them are endemic). Due to its edible fruits and medicinal properties, Annona is the most important genus of Annonaceae family. Despite Annona having many species, only limited species of this family are economically important such as A. squamosa L. (sugar apple), A. cherimola Mill. (Cherimoya), A. muricata L. (guanabana or soursop), A. atemoya Mabb. (atemoya), a hybrid between A. cherimola and A. squamosa, A. reticulata L. (custard apple), A. glabra L. (pond-apple) and A. macroprophyllata Donn. Sm. (ilama). Phytochemically, several classes of secondary metabolites such as acetogenins, essential oils, alkaloids, terpenoids and flavonoids have been described in this genus. A variety of pharmacological activities have been reported from various parts of Annona species specially leaves and seeds including applications against antibacterial, anticancer, antidiabetic and anti-inflammatory.

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites (e.g., exosites, ectosites) through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches such as proteomics and N-terminomics to identify new MMP substrates and achieve a better understanding of the roles of these proteases in diseases.

Medicinal mushrooms have got much attention from biologists in the last decades. Leucocalocybe mongolica Imai remains one of the famous clinical and edible mushrooms used in traditional Chinese medicine and Mongolian medicine to treat various diseases. It also commonly consumes in Chinese and Mongolian daily dishes. Numerous biochemical components exist in L. mongolica, especially in the fruiting bodies include; polysaccharides, sterol, lectins, laccase, amino acids, terpenes, volatile compounds, and so on. These biomedical components possess a lot of medicinal properties and provide diverse therapeutical effects for human health, such as anti-tumor activity, antiproliferative activity, anti-diabetes properties, hypotensive effect, hepatoprotective effect, antioxidant activity, cardioprotective effect, and so on. However, this review's main objectives are to illustrate some basics about the bioactive components in L. mongolica and its pharmacological effects on the human body. In addition to giving forward some suggestions for future research on this medicinal mushroom.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology, with a major genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, the presence of autoantigens and several external factors. The major act of IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation leading to the development of psoriatic lesions. Genome wide association studies (GWAS) along offered a better view of psoriasis pathogenic pathways, with approximately one third of psoriasis genetic impact on psoriasis development is associated to MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Between the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, exhibiting less variety and the involvement of pathogenic bacteria, cand induce a burst of proinflammatory consequences, both cutaneous and gut microbiome being involved in psoriasis pathogenic process. A complex understanding of the major pathways that interplay in order to initiate and perpetuate psoriatic diseases and its associated comorbidities can help the current clinical practice by properly evaluating completely and individualized each patient and establish the proper therapeutic management.

Pleione is a genus of Orchidaceae and is one of the major sources of Pseudobulbus Cremastrae seu Pleiones (PCsP). It contains many constituents, such as phenanthrene, bibenzyl, glycoside, flavonoid and so on, which have plenty of bioactivities, including anti-tumor, anti-oxidation, anti-inflammatory, lowering glycemic levels and other pharma cological activities. In order to further utilize the edible and medicinal functions of Pleione, and clarify its medicinal active ingredients, this review systematically summarizes the constituents and pharmacological effects of Pleione, which will provide a theoretical foundation for the clinical application and new drug development．

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

Plants belonging to the genus Irvingia are widespread across the African and Southeast Asian regions of the world. Irvingia gabonensis, Irvingia malayana, and Irvingia grandifolia are among the commonly used species in ethnomedicine, especially in Africa. Fever, scabies, toothache, inflammation, and liver and gastrointestinal disorders are among the pathological conditions that are reverted by Irvingia plants upon traditional preparations. Modern pharmacological investigations have substantiated the ethnomedicinal uses of Irvingia spp. Reports on the phytochemical analysis of Irvingia plants have revealed the presence of a number of secondary metabolites, such as flavonoids, phenolic compounds, tannins, saponins and alkaloids. Based on the foregoing, the present study provides a comprehensive evaluation of reports on the ethnomedicinal use, phytochemistry, pharmacology, and toxicity of plants from the genus Irvingia. Relevant information on Irvingia plants was mostly obtained from major scientific databases from their inception until July 2023. As a result, more than forty compounds have been identified in Irvingia spp. proving the abundance of secondary metabolites in these plants. Reports have pointed out modern pharmacological activities, such as antiprotozoal, antimicrobial, antioxidant, antidiabetic, anti-inflammatory, and hepatoprotective activities. The present study provides more insights for the successful utilization of Irvingia plants and may guide further research on their therapeutic potential in the treatment of various diseases.

Bioactive plant compounds, also known as phytochemicals, are essential for plant resistance, growth, and development. These chemicals often possess therapeutic properties that have been used in traditional medicine for centuries as herbal remedies for a variety of diseases. As a member of the Lamiaceae family, Rydingia (Syn: Otostegia) is found in Asia and northeastern Africa. R. michauxii, is a unique shrub that grows in the Southern region of Iran, Fars province. Rydingia species have been used as traditional herbal medicine in Iran for many years. It seems that R. michauxii offers great potential for in-depth research on its diverse biological properties, especially its antioxidant and lipid-lowering effects. Nevertheless, no clinical investigation has been carried out on the phytochemical characteristics of this plant to date. Therefore, this study aims to contribute to the scientific knowledge on the pharmacological properties of R. michauxii and its phytochemical compounds and encourage researchers to evaluate its biological properties in animal models. In this study, all available scientific literature was compiled and all phytochemical and pharmacological properties of the R. michauxii plant were investigated, including antibacterial, antifungal, antiviral, antioxidant, antimalarial, cytotoxic, and lipid-lowering effects, which may prove useful in developing novel formulations with greater therapeutic benefits in clinical applications.

Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.

Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries (China, Japan, Korea, Taiwan, Vietnam and India), where it has been used as a valuable source of culinary and traditional medicinal uses. Leaves, seeds and stems of P. frutescens are used for various therapeutic applications in folk medicine. In the absence of comprehensive review regarding all aspects of perilla, thus this review aims to present an overview pertaining to the botanical drug, ethnobotany, phytochemistry and biological activity. It was found that the taxonomic classification of perilla species is quite confused, and the number of species is vague. Perilla has traditionally been prescribed to treat depression-related disease, anxiety, asthma, chest stuffiness, vomiting, cough, cold, flus, phlegm, tumour, allergy, intoxication, fever, headache, stuffy nose, constipation, abdominal pain, indigestion, analgesic, anti-abortive agent, and sedative. Until now, 271 natural molecules have been identified in perilla organs including; polyphenols, flavonoids, essential oils, triterpenes, carotenoids, phytosterols, fatty acids, tocopherols and policosanols. In addition to solvent extracts, these individual compounds (rosmarinic acid, perillaldehyde, luteolin, apigenin, tormentic acid, isoegomaketone) have attracted researchers' interest for pharmacological properties. Its bioactivity showed antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, neuroprotection activity. Although the results are promising in preclinical studies (in vitro and in vivo) as well, clinical studies are insufficient, therefore further study needs to be done to validate its therapeutic effects and to ensure its safety and efficacy.

Quercetin is a flavonoid with a low molecular weight that belongs to the human diet's phenolic phytochemicals and non-energy constituents. Quercetin has a potent antioxidant capacity, being able to capture Reactive Oxygen Species (ROS), reactive nitro-gen species (RNS), and Reactive Chlorine Species (ROC), which act as reducing agents by chelating transition metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, it was described different pharmacological properties of Quercetin, such as carcinostatic properties, antiviral, antihypertensive, anti-inflammatory, protection of Low-Density Lipoprotein (LDL) oxidation, and inhibi-tion of angiogenesis are developed in this review.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Medicinal and aromatic plants are gaining more importance because of their potential application in food, pharmaceutical and fragrance industry. Medicinal and aromatic plants have been used in cosmetics, perfumery, pharmaceuticals and food flavoring since ancient times, because of the presence of essential oils and different components. Seeds are of immense economic and biological importance, and they contain high oil, protein and starch reserves. The seeds of medicinal and aromatic plants are stores of important and active secondary metabolites that have been economically and commercially beneficial and helpful for medicine and pharmacy. The seeds of fennel are highly nutritious, and the seeds contain different minerals such as calcium, magnesium, and potassium. The seeds are helpful in weight loss and cancer prevention. They can also improve digestive health, regulate blood pressure, improve skin appearance, and promotes lactation. The main chemical components of lavender are linalool, linalyl acetate, 1,8-cineole, β-ocimene, camphor and terpinen-4-ol. The lavender essential oil has anxiolytic, anti-inflammatory, antimicrobial, antioxidant and antinociceptive activities.The main components of thyme are p-cymene, γ-terpinene and thymol. Thyme can help to improve eyesight, and it has high anti-bacterial and anti-inflammatory activities. The main compounds of Echinacea species are chlorogenic acid, caftaric acid, cynarin, echinacoside and cichoric acid. The keyword searches for Fennel, Lavender, Thyme, Echinacea, Seed biology, Traditional medicinal science and seed anatomy were performed by using Web of Science, Scopus, PubMed and Google scholar. The aim of this article review is to survey the pharmacological and health benefits of seeds of important medicinal plants.

Syphilis continues to be a significant global health concern, and understanding the latest advancements in immunology and pharmacological treatment is crucial for effective disease management. This review article provides an in-depth exploration of these advancements, aiming to contribute to the growing body of knowledge on syphilis research. The epidemiology of syphilis sets the stage for this review, highlighting the persistent burden of the disease worldwide. Current trends and challenges in disease control are discussed, shedding light on the need for comprehensive prevention strategies and improved surveillance systems. The immunological aspects of syphilis are the focus of this review. The intricate interplay between the host immune response and the evasive strategies employed by Treponema pallidum, the causative agent of syphilis, are explored. These include the mechanisms of immune evasion, the role of adaptive and innate immunity, and the development of immune-mediated tissue damage. The article also highlights advancements in diagnostic methods, with emphasis on the importance of accurate and timely detection. From traditional serological tests to the emergence of novel molecular and point-of-care assays, these developments have significantly improved the efficiency and accuracy of syphilis diagnosis. In terms of pharmacological treatment, the review covers the current recommendations and emerging strategies for managing syphilis infections. The challenges posed by antimicrobial resistance are addressed, emphasizing the importance of appropriate treatment regimens and close monitoring of therapeutic efficacy. Looking to the future, this review highlights the potential of vaccine development as a preventive measure against syphilis. Promising vaccine candidates and ongoing research efforts are discussed, offering hope for an effective means of disease prevention. In conclusion, this comprehensive review explores the advancements in syphilis research, from the understanding of immunological complexities to the development of innovative treatment strategies. By collectively advancing our knowledge, we can strive towards better disease management and minimize the impact of syphilis on global public health.

Knowledge about pharmacological benefits of different seeds is an important factor for cultivation and application of medicinal herbs and plants. The seeds of medicinal plants are stores of valuable and active secondary metabolites that have been commercially and economically beneficial and helpful for medicine and pharmacy. The major parameter of reproduction and preservation of plants are also seeds which have a functional role in the distribution and establishment of plant in different regions. Five important seeds which have tremendous medicinal and pharmacological benefits are anise, basil, borage, cilantro and chamomile. Anise seed is used as a spice, either whole or ground, and its essential oil and extract are also obtained from the seeds. Basil seeds have a long history of usage in Chinese and Ayurvedic medicine, which are the good source of minerals, high in fiber including pectin, rich is flavonoids and other polyphenols. Borage seed oil is used for skin disorders such as seborrheic dermatitis, atopic dermatitis, and neurodermatitis. Cilantro is an annual herb that is part of the Apiaceae family. The seeds are rich in iron, zinc, copper and essential minerals which can decrease bad cholesterol and improves good cholesterol in the body. Chamomile can be considered for treatment of insomnia, hemorrhoids, anxiety, diarrhea and may help with wound healing and skin irritation. The keyword searches for Anise, Seed, Basil, Borage, Cilantro, Chamomile, Seed biology, Traditional medicinal science and seed anatomy were performed by using Scopus, Web of Science, PubMed and Google scholar. The aim of this article review is to survey the pharmacological and health benefits of seeds of five important medicinal plants.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. Management of sleep-wake circadian disorders (SWCD) includes education to sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e. positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially, or can be a combination of several forms of therapy. Drugs used for SWCD include traditional sleep or wake-promoting agents, chronotherapeutic agents. Recently, novel medications, which are more precisely acting on specific neurochemical systems (i.e. orexin system) important for sleep and wake, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

Chaenomeles plants are adapted to diverse ecological zones particularly the temperate areas of Korea, Japan and China. In China, Chaenomeles speciosa mainly planted in Chongqing, Anhui and Hubei provinces. Most of the studies till date have been focused on the anti-inflammatory activities of C. speciosa fractions. The present study aimed to review the maximum literature reported for the presence of various phytochemicals in C. speciosa. In addition, the pharmacological properties of these chemical compounds of this plant shall also be discussed. The extracts of the various parts of the plant are rich in diversity of antioxidants, organic acids, phenolics, terpenoides and many different phytochemicals that bear strong anticancer, antioxidant, anti-viral, antibacterial properties, anti-inflammation, anti-hyperlipidemic, anti-hyperglycemic and anti-parkinson properties. C. speciosa fruits have broad scope in industry as well as in medicines. Not only the leaves and fruits of C. speciosa plant, but various other parts including roots, seeds, bark twigs, and flowers all have long history of clinical trials in curing many human ailments. However, the maximum accessible data concerning the chemical composition and their broad pharmacological properties of C. speciosa plant parts is pretty restricted that make it more appealing for indepth investigations.

Leptadenia reticulata (Ritz.) Wight (Asclepiadaceae), a traditional medicinal plant species, is widely used in traditional medicine to treat various ailments such as tuberculosis, hematopoiesis, emaciation, cough, dyspnea, fever, burning sensation, night blindness, cancer, and dysentery. In Ayurveda, it is known for its revitalizing, rejuvenating, and lactogenic properties. This plant is one of the major ingredients in many commercial herbal formulations, including Speman, Envirocare, Calshakti, Antisept, and Chyawanprash. The therapeutic potential of this herb is because of the presence of diverse bioactive compounds such as α-amyrin, β-amyrin, ferulic acid, luteolin, diosmetin, rutin, β-sitosterol, stigmasterol, hentriacontanol, a triterpene alcohol simiarenol, apigenin, reticulin, deniculatin, and leptaculatin. However, most biological studies on L. reticulata are restricted to crude extracts, and many biologically active compounds are yet to be identified in order to claim the traditional uses of L. reticulata into evidence-based uses. At present, L. reticulata is a threatened endangered plant because of overexploitation, unscientific harvesting, and habitat loss. The increased demand from pharmaceutical, nutraceutical, and veterinary industries has prompted its large-scale propagation. However, its commercial cultivation is hampered because of the non-availability of genuine planting material and the lack of knowledge on its agronomical practices. In this regard, micropropagation technique will be useful to obtain true-to-type L. reticulata planting materials from an elite germplasm to meet the current demand. Adopting other biotechnological approaches such as synthetic seed technology, cryopreservation, cell culture, and genetic transformation can warrant conservation as well as increased metabolite production from L. reticulata. The present review summarizes scientific information on the botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects of L. reticulata. This comprehensive information will certainly allow better utilization of this industrially important herb towards the discovery of lead drug molecules.

The publication presents an innovative tower cultivation device designed to significantly increase vertical farming efficiency. The device divides the cultivation system into separate chambers. One division corresponds to the different growth phases of the plants, while another reflects the daily variation in conditions. Each chamber presents slightly different conditions and cultivation patterns from the others. For the early stages, crops are grown horizontally in trays once they mature, transplanted into mobile cultivation towers. The closed circulation of ventilation and irrigation reduces water consumption by up to 95%. A unique separate day-night division optimises light, temperature and humidity conditions, mimicking natural growth patterns. This approach not only saves water and energy but also optimises cultivation in a three-dimensional space. The presented solution focuses on the often overlooked aspects of cultivating in vertical farms and makes this method of growing much more cost-effective and feasible to implement on a large scale.

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development.

Drowsiness is a main factor for various costly defects, even fatal accidents in areas such as construction, transportation, industry and medicine, due to the lack of monitoring vigilance in the mentioned areas. The implementation of a drowsiness detection system can greatly help to reduce the defects and accident rates by alerting individuals when they enter a drowsy state. This research proposes an Electroencephalography (EEG) based approach for detecting drowsiness. EEG signals are passed through a preprocessing chain composed of artifact removal and segmentation to ensure accurate detection followed by different feature extraction methods to extract the different features related to drowsiness. This work explores the use of various machine learning algorithms such as Support Vector Machine (SVM) the K Nearest Neighbor (KNN) the Naive Bayes (NB) the Decision Tree (DT) and the Multilayer Perceptron (MLP) to analyze EEG signals sourced from the DROZY database, carefully labeled into two distinct states of alertness (awake, and drowsy). Segmentation into 10-second intervals ensures precise detection, while a relevant feature selection layer enhances accuracy and generalizability. The proposed approach achieves high accuracy rates of 99.84% and 96.4% for intra (subject by subject) and inter (cross-subject) modes, respectively. SVM emerges as the most effective model for drowsiness detection in the intra mode, while MLP demonstrates superior accuracy in the inter mode. This research offers a promising avenue for implementing proactive drowsiness detection systems to enhance occupational safety across various industries.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

The enhancement of human living conditions has resulted in an increase in average life expectancy, giving rise to a novel social and medical challenge: aging, which diminishes the overall quality of human life. The aging process of the body begins through the activation of effector signaling pathways of aging in cells, loss of their normal functions and deleterious effects on the microenvironment, which leads to chronic inflammation and similar transformation of neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated mortality risk. Among the most encouraging methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. The review explores the strategies and advancements in the field of anti-aging therapies that are currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

Diabetes mellitus remains a major risk factor for developing cardiovascular diseases, resulting in increased morbidity and mortality associated with cardiovascular complications. Given the burden of diabetes-related cardiovascular complications, there is a need to identify strategies, safe and effective therapeutic agents that could effectively prevent and control diabetes. Presently, many patients living with diabetes depends on traditional medicines as an alternative cure. Channa striatus (Haruan) is a freshwater fish traditionally used to treat wounds, inflammations, and pains. Several pharmacological investigations have supported the folkloric claims of C. striatus extracts, including hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, and pro-platelet aggregation activities. The therapeutic potentials of C. striatus were demonstrated to be associated with the presence of high content essential amino acids and good fatty acids known to improve cell growth and facilitate wound healing. Therefore, C. striatus bioactive compounds have great potentials to serve as lead candidates in developing novel therapeutic agents for the management of diabetes and related cardiovascular diseases. This review aims to provide a comprehensive overview of the pharmacological properties and therapeutic potentials of C. striatus for the management of diabetes and associated cardiovascular complications.

Solidago virgaurea L. (European goldenrod, Woundwort), Asteraceae, is a familiar medicinal plant in Europe and other parts of the world, widely used and among the most researched species from its genus. The aerial parts of European goldenrod have long been used for urinary tract conditions and as an anti-inflammatory agent in the traditional medicine of different peoples. Its main chemical constituents are flavonoids (mainly derived from quercetin and kaempferol), C6-C1 and C6-C3 compounds, terpenes (mostly from the essential oil), and a large number of saponin molecules (mainly virgaureasaponins and solidagosaponins). Published research on its potential activities is critically reviewed here: antioxidant, antiinflammatory, analgesic, spasmolitic, antihypertensive, diuretic, antibacterial, antifungal, antiparasite, cytotoxic and antitumor, antimutagenic, antiadipogenic, antidiabetic, cardioprotective, and antisenescence. The evidence concerning its potential benefits is mainly derived from non-clinical studies, some effects are rather modest, whereas others are more promising, but need more confirmation in both non-clinical models and clinical trials.

Human eye is a specialized organ with complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years many in vitro models have been developed, in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review the ocular cell types and functionality are described providing an overview about the scientific challenge for the development of three-dimensional in vitro models.

Mulberry (Morus) cultivated worldwide in diverse agro-ecological conditions recognized as the fodder of silkworms (Bombyx mori). In India, ranging from high altitude Himalayan region to coastal region, the farmers generally cultivate these four species of mulberry (Morus alba, M. indica, M. serrata, and M. laevigata). Mulberry fruit is used in traditional medicine for several years in China and also consumed as food material in different countries of Asia and Africa. Mulberry fruit, along with high nutritious value, contains many bioactive phytochemicals that are30 of health benefits and can fight against many diseases. Many researchers attracted to this property of mulberry fruit, and they isolated bioactive polysaccharides, anthocyanins, flavonols, flavonols, phenolic acids, alkaloids, and melatonins. These compounds have antioxidant property and due to this, either in synergistically or in the pure form, these components have direct or indirect curative activity on diabetes, inflammation, tumor, hepatic diseases, immunomodulation, hyperlipidemia, neural damage, and chronic diseases. This tremendous bioactivity of mulberry fruit extract may open up a new dimension in the food and medicine industry. The present review provides recent findings of the phytochemical foundation and their bioactivities, which may encourage many researchers to explore the molecular mechanism of the biological activities which can be used for human welfare.

Penicillium digitatum is the major postharvest pathogen of citrus fruit under Mediterranean climate conditions. In the present work, we have addressed the study of the role of P. digitatum’s proteases in virulence following two complementary approaches. In a first approach, we have undertaken the functional characterization of the P. digitatum prtT gene, which codes for a transcription factor previously shown to regulate extracellular proteases in other filamentous fungi. Deletion of prtT caused a significant loss in secreted protease activity during in vitro growth assays. However, there was no effect on virulence. Gene expression of the two major secreted acid proteases was barely affected in the ΔprtT deletant during infection of citrus fruit. Hence, no conclusion could be drawn on the role of these secreted acidic proteases on the virulence of P. digitatum. In a second approach, we have studied the effect of different protease inhibitors and chelators in virulence. Co-inoculation of citrus fruit with P. digitatum conidia and a cocktail of protease inhibitors resulted in almost a complete absence of disease development. Analysis of individual inhibitors revealed that the metalloprotease inhibitor 1,10-phenanthroline was responsible for the observed effect. The application of metal ions reverted the protective effect caused by the metallopeptidase inhibitor. These results may set the basis for the development of new alternative treatments to combat this important postharvest pathogen.

With more companies entering the realm of electric vertical take-off and landing (eVTOL), and governments enacting policies to support the development of low-altitude economies, the commercial potential of eVTOL is being recognized by the public. However, true commercialization is still a long way off. This article analyzes the technologies, product features, potential markets, and government policies related to eVTOL, and constructs a four-stage, four-layer Policy-Technology Roadmap (P-TRM) model to guide the R&D process of eVTOL. Then transform it into a system structural model, and the Decision-making Trial and Evaluation Laboratory (DEMATEL) method is used to identify several key nodes in the R&D process. Utilizing the Technology Adoption Life Cycle (TALC) theory for interpretation and analysis, the article concludes by proposing strategies in product, technology, and policy support for how eVTOL can successfully cross the chasm. This preliminary analysis of the development path, key nodes, and necessary measures for crossing the chasm provides insights for the R&D and commercialization of eVTOL.

Snow crab replaced groundfish fisheries as the primary focus of the Newfoundland and Labrador (NL) fishing industry in the mid-1990s. Over the past three decades, management philosophies in this male-only fishery have shifted from promoting industry expansion to promoting industry rationalization to implementing Precautionary Approach (PA) management. Until the mid-2010s, there were regionalized management strategies characterized by higher exploitation rates in northern than southern sub-stock units along the NL marine shelves. However, in the late 2010s, exploitation rates were permitted to elevate to high levels across the entire stock range in association with a large resource decline and evidence of biological harm through fishing emerged in chronically depleted areas. In 2019, when stock and fishery productivity were near historic lows, a multi-indicator PA system was informally introduced into management of the resource. This event coincided with anticipated improvements in stock and fishery performance. This paper examines the extent to which the multi-indicator PA management system, focused on promotion of both biological protection and maximization of fishing efficiency, may have contributed to recent improvements in stock and fishery status. A suite of indicators from areas implementing PA guidance into management in 2019 prior to formal adoption of the PA system in 2023 suggest the system has been highly beneficial in promoting rapid recovery, improving stock and fishery performance metrics to levels matching or exceeding historic levels under similar conditions. We discuss capacity of the system to better safeguard biological aspects of resource and fisheries productivity moving forward under a scenario of an expectant resource decline.

As modern systems are becoming more complex their control strategy cannot longer relay only on measurement information that usually comes from probes but also from mathematical models. Those systems models can lead to unbearable computation times due to their own complexity, turning the control process non-viable, which leads to the implementation of surrogate models that enable to achieve estimates within acceptable time to take decisions. A control trained with Deep Reinforcement Learning algorithm, using a Physics-Informed Neural Network to obtain the temperature map on the following time step, replaces the need of running Direct Numerical Simulations. On this work we considered an 1D heat conduction problem, which temperature distribution feeds a control system to activate a heat source aiming to obtain a constant, previously defined, temperature value. With this approach, control training becomes much faster without the need of performing numerical simulations or laboratory measurements, as well the control is taken based on Neural Network enabling its implementation on simple processors to edge computing.

Interaction between multiple phases especially liquid-gas is one of the most common phenomena in industrial systems. Computer Vision enables modern systems to derive an automated and robust image-processing technique to address this issue. However, diverse experimental conditions still make it a challenging task to overcome. In Deep Learning, instance segmentation has created a niche in various computer vision applications as it aims to provide different instance IDs to objects belonging to the same class. In this paper, we propose a novel approach employing the YOLO (You Look Only Once) an end-to-end deep learning architecture for the detection and segmentation of bubbles in fluid flows. YOLOv5 offers significant improvements in both speed and accuracy compared to its predecessors like YOLOv3. Therefore, we train the YOLOv5 network on a dataset consisting of annotated images representing instances of bubbles across varied fluid flow environments. This paper provides both qualitative and quantitative evaluation of three YOLOv5 networks (small, medium, and extra-large) in detecting and segmenting bubbles with high accuracy and efficiency. Based on the metrics all three YOLOv5 models achieved high precision above 0.98 for bounding box detection and 0.97 for segmentation mask, and high recall value greater than 0.97 for box and 0.96 for mask quality was achieved. The achieved results indicate that the models accurately localize bubbles within the image frame, and distinguish bubble pixels from the background. Also, mean average precision (mAP50-95) consistently exceeds 0.84 across all models for the bounding box and 0.73 for the segmentation mask. The ascertained results emphasize the potential of YOLOv5 architecture as a powerful tool for automated bubble analysis in real-world applications. Our research contributes to advancing the field of deep neural networks in fluid systems and provides a fresh approach for future developments in automated bubble analysis.

Particulate matter (PM) is one of the problems faced in environmental science. It has health effects on man and animals in both developed and developing countries. Research and efforts have been on it several years back. Policy statements and efforts have been published. This review paper is an added information on air pollution. In it, efforts were made in discussing these: classification, effects, methodology, case studies and source apportionment. It is hoped that this paper would contribute to existing knowledge on PM.

Curcumin, a hydrophobic bioactive constituent from Curcuma longa, has several health promoting properties including anti-atherosclerotic properties. Further, curcumin has blood glucose- and lipid-lowering properties, prophylactic, and therapeutic effects in other cardiometabolic diseases. Atherosclerosis is an umbrella term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large and medium -sized artery walls that decrease vascular-wall elasticity and lumen diameter. The atherosclerotic cerebro-cardiovascular disease has become a major concern to human health in recent years. Considering the notable cardiovascular actions of curcumin, the present review summarizes the current status and future perspective of research on curcumin and its ability to prevent or treat atherosclerosis

Geothermal energy, being a clean energy source, has immense potential, and accurate wellbore modeling is crucial for optimizing the drilling process and ensuring safety. This paper presents a novel geothermal wellbore model based on the drift-flux approach, tested under three different temperature and pressure well conditions. The proposed model integrates the conservation equations of mass, momentum, and energy, incorporating the gas-liquid two-phase flow drift-flux model and heat transfer model. Key features include handling heat transfer between the for-mation and the wellbore, addressing the slip relationship between gas and liquid phases, and accounting for wellbore friction. The nonlinear equations are discretized using the finite differ-ence method, and the highly nonlinear system is solved using the Newton-Raphson method. Numerical simulation, validation, and comparison with existing models demonstrate the en-hanced accuracy of this model. In our tests, the model achieved high accuracy in calculating bottom hole pressure and temperature, with Mean Relative Errors (MRE) significantly lower than those of other models. These results offer valuable insights for optimizing drilling parameters and ensuring drilling safety. Comparisons indicate that this approach significantly outperforms others in capturing the complex dynamics of geothermal wellbores, making it a superior tool for geo-thermal energy development.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Electronic waste generation has been following a continuously rising trend. With electronics containing a myriad of materials some of which are hazardous, toxic, extremely rare or precious combined with more stringent legislative laws which encourage the reuse and optimised recycling of the materials included in e-waste, the need for a holistic approach is inevitable. Such an approach should not only identify the materials found in the various types of e-waste and their respective quantities but also needs to highlight the possible handling techniques and their respective impacts and associated hazards whether to the environment or human health. Performing such a task manually would be exasperating and costly while requiring extensive resources which might not be met with a justifiable economic gain; thus, the use of the advancement in computational sustainability to draw a complete picture and aid in an informed decision-making process is crucial. The e-waste ontology developed in this paper is one way of addressing the problem since it covers the treatment domain, the hazard and the materials contained within the different types of e-waste. The ontology developed can be used directly from the protégé software or by embedding it into a developed Decision Support System.

Toll plaza optimization is essential for improving traffic flow and easing congestion on road networks. This study aims to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer facilitation. Different resources are used for data collection, like the National Highway Authority of Pakistan. Physical data is collected from the established Toll Plaza of Peshawar, along with the development of each line. The goal of this study is to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer happiness. The analysis of present traffic patterns, the detection of bottlenecks, and the creation of plans to ease congestion and enhance overall traffic flow are all part of the optimization process. The approaches used in this study include data analysis, simulation, and traffic modeling. PTV VISSIM is software for transportation planning, design, and analysis. The simulations consider various conditions, such as variable traffic volumes, toll collection methods, and lane configurations. When comparing the different optimization strategies, performance indicators like trip time, latency, and queue length are utilized to determine which approach is practical. Waiting time Vs. Existing each lane, etc, is explained. In the end, comparing queue lengths and throughput across different lane scenarios shows that maximizing throughput with existing lanes yields up to 45% improvement with E-tag lanes, 40% with existing E-tag lanes, 38% with E-tag plus additional toll and cash lanes, 32% with three cash lanes, and 28% with two E-tag lanes. Failure to regularly monitor and adjust the existing lane pattern scenario based on traffic patterns can lead to queues being 20% longer. Without proactive evaluation and optimization, there is a potential 63% opportunity for queue length improvement

Multimodal emotion classification (MEC) involves analyzing and identifying human emotions by integrating data from multiple sources, such as audio, video, and text. This approach leverages the complementary strengths of each modality to enhance the accuracy and robustness of emotion recognition systems. However, one significant challenge is effectively integrating these diverse data sources, each with unique characteristics and levels of noise. Additionally, the scarcity of large, annotated multimodal datasets in Bangla limits the training and evaluation of models. In this work, we unveiled a pioneering multimodal Bangla dataset, MAViT-Bangla (Multimodal Audio Video Text Bangla dataset). This dataset, comprising 1002 samples across audio, video, and text modalities, is a unique resource for emotion recognition studies in the Bangla language. It features emotional categories such as anger, fear, joy, and sadness, providing a comprehensive platform for research. Additionally, we developed a framework for emotion recognition that employs a cross-modal attention mechanism among unimodal features. This mechanism fosters the interaction and fusion of features from different modalities, enhancing the model’s ability to capture nuanced emotional cues. The effectiveness of this approach was demonstrated by achieving an F1-score of 0.64, a significant improvement over unimodal methods.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

This article describes the challenges, pharmacological strategies, and recommendations for managing multidrug-resistant breast cancer in Sub-Saharan Africa (SSA). By examining the current breast cancer treatment landscape, region-specific challenges, and promising pharmacological interventions, the objective is to bring to light the insufficient research on breast cancer and its multidrug resistance in this part of the world and guide healthcare professionals, policymakers, and researchers in developing evidence-based strategies for improved breast cancer care in SSA. Breast cancer is the leading cause of cancer morbidity in SSA, necessitating continuous advancements in its management. This overview explores the evolution of breast cancer treatment, including surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Despite these advancements, multidrug resistance poses a significant challenge, impacting treatment efficacy and patient outcomes.The article provides insights into various breast cancer treatment modalities, emphasizing surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Each approach is discussed in detail, highlighting its significance in managing breast cancer. The effectiveness of these treatments is contingent on timely diagnosis and intervention. Multidrug resistance is examined as a critical obstacle in breast cancer treatment, elucidating its impact on treatment failure and patient outcomes. Mechanisms such as the efflux system, enhanced DNA repair, apoptosis inhibition, alterations in drug targets, and the tumor microenvironment contribute to multidrug resistance, emphasizing the need for a multifaceted understanding.The unique challenges faced in SSA regarding multidrug-resistant breast cancer are delineated. These include the lack of comprehensive data, late presentation and diagnosis, poor genomic studies, limited access to specialized care, financial constraints, inadequate infrastructure, and psychosocial support issues. Addressing these challenges is crucial for devising effective strategies. In response to multidrug resistance, the article discusses contemporary treatment strategies such as P-glycoprotein inhibitors, combined chemotherapy, and immunotherapy. Notable advancements, including the use of Tariquidar and synergistic effects of combined chemotherapy, are highlighted, presenting promising avenues for overcoming resistance.The article proposes recommendations to enhance breast cancer management in SSA, encompassing strengthening primary healthcare services, creating specialized oncology facilities and long-term monitoring and data collection. Breast cancer management in SSA is multifaceted, marked by challenges and evolving solutions. Multidrug resistance remains a significant hurdle, demanding a holistic approach. Promising advancements in pharmacological interventions offer hope, while comprehensive recommendations serve as a roadmap for progress. By implementing these strategies, SSA can substantially improve multidrug-resistant breast cancer care and overall patient well-being.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Euryale ferox, which belongs to the family of Nymphaeaceae, has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on its abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literatures (since 1980), medical classics, databases, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for the further research and development of EFS-derived functional products.

Non-pharmacological interventions in the fight against COVID 19 include: a) suppression, which facilitates its extinction; and b) mitigation, which reduces its speed of spread. Left unmitigated, the intensive care unit bed capacity (ICU) is exceeded over its maximum supply, resulting in increased deaths. Suppression has shown in simulation models the potential for decreasing ICU occupation below its surge limit, effectively decreasing mortality. However, for avoiding a rebound in transmission, suppression must be maintained intermittently until a vaccine is available (which may take up to 2 years). The objective of this paper was to describe the mortality patterns observed in Spain, Italy and South Korea for discussing a hypothetical combined public health policy and socioeconomic model that could potentially reduce mortality while reducing the economic impact of this pandemic in Spain. The plan is based on a progressive-voluntary reinstatement to work of the population exposed to the lowest risks (healthy non-immune family units <50 y/o and immune population) and it depends on having sufficiently available ICU beds for providing adequate support. This model, if proven correct for Spain, could eventually be followed by other countries facing a similar impact of the present pandemic.

Snakebite envenomation, cognized as a neglected tropical disease, is a dread public health concern with the most susceptible groups being herdsmen, the elderly, active farmers, hunters, fishers, firewood collectors, 10 to 14-year old working children and individuals with limited access to education and health care. Snakebites are fragmentarily documented in Uganda primarily because most occur in rural settings where traditional therapists end up being the first line defence for treatment. Ethnobotanical surveys in Uganda have unveiled that some plants are used to antagonize the activity of various snake venoms. This review was sought to compile the sporadic information on the vegetal species reported as antivenins in Uganda. Electronic data indicate that no study entirely reported on antivenin plants in Uganda. A total of 77 plant species belonging to 65 genera, distributed among 42 botanical families claimed as antiophidic in Uganda are used for treatment of snakebites. Majority of these species belong to family Fabaceae (30.9%), Euphorbiaceae (14.3%), Asteraceae (11.9%), Amaryllidaceae (9.5%) and Solanaceae (9.5%). The antiophidic species listed are shrubs (40.5%), trees (32.9%) and herbs (17.7%), usually found in the wild and uncultivated. Antivenin extracts are primarily prepared from roots and leaves, through decoctions, infusions, powders and juices and administered orally or topically. The most frequently encountered therapeutically important species are Allium cepa L., Carica papaya L., Securidaca longipedunculata Fres., Harrisonia abyssinica Oliv. and Nicotiana tabacum L. Baseline epidemiological data on snake envenomation and antivenin plants in Uganda remain incomplete due to inadequate research and diverse ethnic groups in the country. There is a dire need to isolate and characterize the bioactive compounds in the claimed plants to enable their adroit utilization in handling the plague of snake envenomation. More baseline data should be collected on snake ecology and human behaviour as well as antivenin plants in Uganda. Indigenous knowledge on the use of plant preparations in traditional medicine in Uganda is humongous, but if this is not quickly researched and appropriately documented, indications as to the usefulness of this vegetal treasure house will be lost in the not so distant future.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Pedestrian trajectories are crucial for self-driving cars to plan their paths effectively. The sensors implanted in these self-driving vehicles, despite being state-of-the-art ones, often face inaccuracies in the perception of surrounding environments due to technical challenges for adverse weather conditions, interference from other vehicles sensors and electronic devices, and signal reception failure, leading to incompleteness in trajectory data. But for real-time decision making for autonomous driving, the trajectory imputation is no less crucial. Previous attempts to address this issue such as statistical inference and machine learning approaches have shown promise. Yet, the landscape of deep learning is rapidly evolving with new and more robust models emerging. In this research, we have proposed an encoder-decoder architecture, Human Trajectory Imputation Model, coined as HTIM, to tackle these challenges. This architecture aims to fill in the missing parts of pedestrian trajectories. The model has been evaluated using the Intersection drone inD dataset, containing trajectory data at suitable altitudes preserving naturalistic pedestrian behavior with varied dataset sizes. To assess the effectiveness of our model, we have utilized L1, MSE, Quantile and ADE loss. Our experiments have demonstrated that HTIM outperforms the majority of the state-of-the-art methods in this field, thus indicating its superior performance in imputing pedestrian trajectories.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

The advent of modern satellite technology has transformed observational astronomy and astrophysics, offering unprecedented insights into the large-scale behavior of gravitation and challenging established cosmological models. This technological progress has reinvigorated the study of relativistic cosmology, leading to a critical reassessment of foundational assumptions, particularly the cosmological principle, which posits that the universe is homogeneous and isotropic on large scales. While this principle underpins the Standard Cosmological Model and the Friedmann-Lemaitre-Robertson-Walker metric, emerging data has increasingly been challenging its validity. Central to this investigation are the redshift-distance and light intensity-distance relations, essential for testing cosmological models. The integration of both parametric and nonparametric redshift models provides a more comprehensive analysis, addressing discrepancies in our understanding of the universe's structure and evolution. However, unresolved mysteries, particularly concerning dark matter and dark energy, complicate these models. This research critically examines the cosmological principle using the latest observational data and scrutinizes the Friedmann model's assumptions. The study shows that galaxy formation was most rapid in the early universe, especially within the redshift range of , with notable peaks around at and These two characteristic redshift values, predicted by our standard Friedmann redshift model used in this work, are confirmed by the observational data utilized in this research. The research also highlights that dark matter plays a significantly more critical role than dark energy in the process of galaxy formation. While dark energy primarily affects the large-scale expansion of the universe, dark matter seems to go beyond the domination of local galaxy formation and evolution of cosmic structures. These findings underscore the limitations of current models and contribute to the ongoing refinement of cosmological theories, offering a clearer understanding of the universe’s evolution.

In his best-selling book An Introduction to Probability Theory and its Applications, W. Feller established a way of ending the St. Petersburg Paradox by the introduction of an entrance fee, and provided it for the case in which the game is played with a fair coin. A natural generalization of his method is to establish the entrance fee for the case in which the probability of head is θ (0 < θ < 1/2). The deduction of those fees is the main result of Section 2. We then propose a Bayesian approach to the problem. When the probability of head is θ (1/2 < θ < 1) the expected gain of the St. Petersburg Game is finite, therefore there is no paradox. However, if one takes θ as a random variable assuming values in (1/2,1) the paradox may hold, what is counter-intuitive. On Section 3 we determine a necessary and sufficient condition for the absence of paradox on the Bayesian approach and on Section 4 we establish the entrance fee for the case in which θ is uniformly distributed in (1/2,1), for in this case there is paradox.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

Gentiopicroside (GPS) is a leading component of several plant species from Gentianaceae botanical family. As a compound with plenty biological activities and a component that is often consumed in dietary supplements and herbal drugs, GPS has an important role in the regulation of physiological processes in humans. Recent studies on the type 2 receptors shed new light on GPS applications showing its agonistic properties that could be meaningful in the future therapeutic strategies of Parkinson’s disease, thyroid disorders or cancer states. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention at the newly discovered role of this bitter-tasting secoiridoid as a type 2 receptor agonist. Thanks to these properties, the research on this substance could be revisited.

To date, recanalization interventions are the only available treatments for ischemic stroke patients, however, there are no effective therapies for reducing stroke-induced neuroinflammation. We recently reported that H+ extrusion protein Na+/H+ exchanger-1 (NHE1) plays an important role in stroke-induced inflammation and white matter injury. In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. Post-stroke HOE642 and Rimeporide treatments accelerated motor and cognitive function recovery without affecting the initial ischemic infarct, neuronal damage or reactive astrogliosis. However, delayed administration of NHE1 blockers after ischemic stroke significantly reduced microglial inflammatory activation while enhanced oligodendrogenesis and white matter myelination, with increased proliferation and decreased apoptosis of the oligodendrocytes. Our findings suggest that NHE1 protein plays an important role in microglia-mediated inflammation and white matter damage. Pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as therapeutic strategy for ischemic stroke therapy.

Background: Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. Methods: We used high resolution all-optical electrophysiology on ex-vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. Findings: We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2) and to a lesser extent in the absence of E4031. Moreover, we show that PUFA analogues slightly shorten the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Interpretation: Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions but plays a more important role when IKr is compromised, as if IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in zebrafish heart.

INTRODUCTION: Cardiovascular prevention is less effective than expected due to the concern about polymedication of professionals and the lack of adherence of patients. Polypills are presented as a possible solution, increasing therapeutic adherence in the medium or long term and improving therapeutic results compared to the administration of drugs separately: they increase effectiveness and Adherence of patients to primary and secondary cardiovascular prevention programs, without increasing the cost of the intervention. OBJECTIVES: Study #Trigeria: to specify the combined prevalence of Atrial Fibrillation, Dyslipidemia and Hypertension and analyze the pharmacological prescription for these pathologies and the possible indications and advantages that would have the prescription of a polypill for these risk factors.METHODS: Observational analytical study on the pathological history in elderly institutionalized in nursing homes and analysis of prescribed oral medication.RESULTS: 169 people analyzed (79.3% women) from 4 nursing homes; 8.9% had a history of Atrial Fibrillation, Dyslipidemia and Arterial Hypertension; these had a higher prevalence of heart disease (42.9%) and Cerebral Vascular Accident (35.7%). Polymedication was present in 88.5%, with an average of 6.94 oral drugs prescribed; among those with the three pathological antecedents, the average number of oral medications was 8.60. Only 26.7% of those with all three factors were prescribed drugs to control them.DISCUSSION: There are high rates of polymedication in the sample and low rates of prescription of antiplatelet agents in people with Atrial Fibrillation (26.5%); the low prescription of statins and antihypertensives of the ACE inhibitor or ARB-II groups may be due to good control with non-pharmacological measures or by the use of other groups of drugs . A polypill holding the drugs that control the three factors studied could increase the prescription rate while simplifying the administration schedule and reducing polymedication by 23.25% improving prescription, increasing adherence and control of risk factors without increasing pharmaceutical expenditure.CONCLUSIONS: There is a low rate of prescription of antiplatelet agents among people with atrial fibrillation. Combination methods (polypills) can increase the suitability of prescriptions in people with polypathology, improving prescribing, simplifying administration and increasing adherence to pharmacological treatments.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The KEGG pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, a combinational effect of the mixture of three herbs was found. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFAs-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Inflammation associated endothelial dysfunction represents a pivotal contributor to atherosclerosis. Increasingly evidence has demonstrated that interleukin 1 receptor (IL1-R) / toll-like receptor (TLR) signaling participated in the development of atherosclerosis. Previous studies indicated the therapeutic potential of anti-inflammatory therapy in anti-atherosclerosis. The present study examined the effect of IL-1R-associated kinase 1 and 4 inhibitors (IRAK1/4i) in regulating endothelial dysfunction. IRAK1/4i showed little endothelial toxicity at concentrations from 1 to 10 μM. Inhibition of IRAK1/4 alleviated endothelial activation induced by LPS in vitro evidenced by attenuated monocyte adhesion to the endothelium. Mechanistically, blockade of IRAK1/4 ameliorated the transcriptional activity of NF-κB. Taken together, our findings demonstrated that dual inhibition of IRAK1 and IRAK4 attenuates endothelial dysfunction, suggesting pharmaceutical inhibition of IRAK1/4 might be a potential strategy to combat endothelial dysfunction and atherosclerosis.

Mobile Edge Computing (MEC) integrated with Wireless Power Transfer (WPT) is emerging as a promising solution to reduce task delays and extend the battery life of Mobile Devices (MDs). Cooperative user communication, or relay technology, enhances communication efficiency for users located far from the base station by mitigating the double near-far effect caused by distance. This is considered a key technology in Beyond 5G (B5G) and future communication systems. In this paper, we focus on maximizing the long-term energy efficiency (EE) of a user-cooperation WPT-MEC system, while taking into account the uncertain load dynamics at the edge MD and the time-varying state of the wireless channel. The joint optimization of wireless charging time fraction, MD offloading duration, helper node processing time, and transfer power decision presents significant challenges due to the coupling of data offloading among cooperative users and a volatile system environment. To address these challenges, we formulate the problem as a stochastic programming problem and propose an online control algorithm, DOUCA, to solve it. Our approach utilizes Dinkelbach’s method and Lyapunov optimization theory to decouple the sequential decision problem into a deterministic sub-problem for each time slot. For the sub-problem, we use variable substitution to convert the non-convex problem into a convex one, containing only a small number of variables, which can be efficiently solved. Furthermore, we provide a mathematical analysis of our algorithm’s performance. Extensive simulation results demonstrate the effectiveness of our proposed algorithm, as evidenced by an impressive energy efficiency improvement of over 20% compared to benchmark methods. Our algorithm also achieves a trade-off between EE and system stability.

Chinese texts often feature a substantial volume of normative content, and their analysis has increasingly become a focal point in recent semantic analysis endeavors. Enhancing the effectiveness of text classification and clustering is pivotal in unveiling the intricate semantics within extensive textual data. Empirical research within the realm of computational social science has underscored the need for improved explanatory power when it comes to general text clustering methods applied to normative texts. This study introduces an innovative hierarchical clustering method that incorporates part-of-speech (POS) features and pioneers a novel semantic network model. It achieves this by amalgamating a POS-based feature weight calculation method with hierarchical clustering techniques. To assess its efficacy, the method is rigorously evaluated across three diverse text datasets, encompassing normative reports, news articles, and social media content. The experimental results unequivocally demonstrate the superior performance of the POS-HC method, surpassing the traditional TF and TF-IDF feature extraction methods in terms of clustering accuracy, and surpassing some existing clustering methods. Furthermore, its classification effectiveness exhibits notable advantages, particularly in the semantic classification of normative texts.

This paper presents an on-device semi-supervised human activity detection system that can learn and predict human activity patterns in real time. The proposed semi-supervised learning (SSL) framework uses sparsely labelled user activity events acquired from Inertial Measurement Unit (IMU) sensors installed as wearable device. The objective is to learn classification of multiple classes of human activities in real-time. The proposed cluster-based learning model in this approach is trained with data from the same target user, thus preserving data privacy while providing personalized activity detection services. Two different cluster labelling strategies, namely, population-based, and distance-based, are employed to achieve the desired classification performance. A comparative study of these strategies has been presented in terms of classifiability and classification accuracies. The proposed system is shown to be computationally efficient, which is relevant in the context of limited computing resources on typical wearable devices. The trade-off between classification accuracy and computation complexity is analyzed for different algorithmic hyper-parameters and other system parameters. Extensive experimentation and simulation study have been conducted on a multi-user human activity data from the public do-main in order to validate the proposed learning paradigm.

Elbow dislocation and instability present significant clinical challenges, necessitating a thorough understanding of the underlying bio-mechanical mechanisms. In this study, a quasi-static three-dimensional finite element model of the human elbow joint is developed to investigate stress distribution and stages of dislocation in the human elbow under various loading conditions. The model simulates the elbow joint in different degrees of flexion (30°, 45°, 60°, and 90°) and forearm positions (pronation and supination), providing detailed insights into the progression of dislocation. Significant findings include the identification of high stress concentrations on the humerus at 90° flexion and on the radial and coronoid processes at 30°, 45°, and 60° flexion. Three reproducible stages of dislocation were observed, particularly in flexed positions with forearm pronation or supination. These stages align with experimental observations and highlight the initial occurrence of bony failures, such as radial head and ulnar coronoid fractures, preceding soft tissue tears. Clinically, the study underscores that early-stage low-impact posterior elbow dislocations retain enough stability to be managed with closed reduction and early mobilization. However, as dislocations progress, significant damage to the medial and lateral collateral ligaments is expected, necessitating more invasive treatments. This research provides valuable bio-mechanical insights into elbow dislocation, aiding in the development of improved treatment strategies and enhancing patient outcomes through precise and timely clinical interventions. The validated FEM serves as a powerful tool for pre-surgical planning offering a comprehensive understanding of elbow joint mechanics.

This study presents a unique model for assessing the dependability of continuous parts of combined systems in open-pit mining through the application of fuzzy logic. Continuous sub-systems as part of the combined system of coal exploitation in surface mines have the basic function of ensuring safe operation, high capacity with high reliability and low costs. These subsystems are usually part of the thermal power plant's coal supply system and ensure stable fuel supply. The model integrates various independent partial indicators of dependability into an expert system specifically designed for evaluating these systems. It deconstructs the complex parameter of system dependability into distinct partial indicators: reliability, maintainability, and logistical support. These indicators are then integrated using fuzzy composition (max-min composition). Historical data from 2018 to 2023 is utilized alongside the fuzzy model to provide a retrospective analysis of system dependability, serving to validate the model's effectiveness. What sets this model apart from conventional approaches is its consideration of practical dependability indicators, thereby obviating the need for extensive long-term monitoring and data collection to portray the system's status accurately over time. This model serves as a valuable tool for assisting decision-makers in open-pit mining operations, facilitating planning, exploitation control, and the selection of maintenance strategies to ensure consistent production and cost reduction. Designed for quick assessment, the model relies on expert judgments and assessments to determine system dependability efficiently.

Despite Low Power Wide Area Networks’ ability to offer an extended range, it might still encounter challenges with coverage blind spots in the network. This article proposes an innovative energy-efficient nature-inspired relay selection algorithm for LoRa-based LPWAN networks, serving as a solution for challenges related to poor signal range in areas with limited coverage. A behavior swarm-inspired approach has been utilized to select the relays’ localization in the network, providing network energy efficiency and radio signal extension. These relays help bridge communication gaps, significantly reducing the impact of coverage blind spots by forwarding signals from devices with poor direct connectivity with the gateway. The proposed algorithm considers critical factors for the LoRa standard, such as the Spreading Factor or device energy budget analysis. The simulation experiments validate the proposed scheme’s effectiveness in terms of energy efficiency under diverse multi-gateway topology scenarios involving thousands of devices. Specifically, it has been verified that the proposed approach outperforms the reference method in preventing the battery depletion of relays, which is vital for battery-powered IoT devices. Furthermore, for some large-scale problems, the proposed heuristic method achieves over twice the speed of the exact method with a negligible accuracy loss of less than 2%.

Omega-3 polyunsaturated fatty acids (ɷ-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of Metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDS). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.

For a long time, a company's Product Development Process (PDP) was seen as supporting the operations department, although PDP decisions and mistakes have a considerable impact on market performance. This is critical even in agriculture where bad habits and practices in the PDP can lead rural producers to great losses. Therefore, this research investigated the effect on the market performance of rural products (banana) in the southern region of Brazil, based on two analyses: (i) how sustainability practices support the PDP phases and (ii) how the phases of the Product Life Cycle Assessment (LCA) mediate sustainability practices and PDP phases. This study presents a quantitative analysis using Confirmatory Factor Analysis (CFA) and hierarchical ordinary least squares (OLS) regression of data obtained from a survey of 110 rural producers who directly participate in the banana production and planning process in southern Brazil. Our results shows that sustainability practices support the PDP, and we confirm that the product development and post-development phase has an effect on market performance. In addition, we identified that in the pre-development phase of the PDP, dealing with rural products (bananas), the maturity stage of the LCA mediates sustainability. In the PDP development phase, we concluded that rural families that develop economic and environmental practices with their products in the market growth phase may have reduced results. As for the post-development phase of the PDP, we conclude that when companies invest in environmental and social practices, there is a complete mediation of the effect, where these practices lose strength if the product is in the introduction and maturity phases in the market. As originality, our study contributed to demonstrate value on the product life cycle for the product development process in agriculture using sustainability practices through a systemic approach, filling the gap in the literature due to the lack of research on these areas seen in an integrated way.

We develop an action principle for producing a single fluid, two-constituent system with dissipation in general relativity. The two constituents in the model are particles and entropy. The particle flux creation rate is taken to be zero, while the entropy creation rate is non-zero. Building on previous work, it is demonstrated that a new term (the proper time derivative of the matter space ``metric'') is required in the Lagrangian in order to produce terms typically associated with bulk and shear viscosity. Equations of motion, entropy creation rate, and energy-momentum-stress tensor are derived. Using an Onsager approach of identifying thermodynamic ``forces'' and ``fluxes'' a model is produced which delivers the same entropy creation rate as the standard, relativistic Navier-Stokes equations. This result is then contrasted with a model generated in the spirit of the action principle, which takes as its starting point a specific Lagrangian and then produces the equations of motion, entropy creation rate, and energy-momentum-stress tensor. Unlike the equations derived from Onsager reasoning, where the analogs of the bulk and shear viscosity coefficients are prescribed ``externally'', we find that the form of the coefficients in the second example are a direct result of the specified Lagrangian. Furthermore, the coefficients are shown to satisfy evolution equations along the fluid worldline; also a product of the specific Lagrangian.

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

Concrete is more stable than filler as a false roof in a downward approach type infill quarry, but the mechanical model of a concrete false roof is not clear. As a result, there has been limited application. Therefore, it is necessary to establish the mechanical model of a concrete artificial false roof to enhance the stability of the downward approach infill quarry. This paper combines theoretical analysis, model derivation, finite element analysis and field application methods. Firstly, the basic assumptions of thin plate theory and elasticity mechanics are used as the premise to establish the differential equations of the deflection curve of the concrete thin plate false roof. Then, the three types of bending moment generation of the concrete thin plate false roof are explored. Secondly, the relationship between the location of dangerous surface and dangerous point in hard-supported weak-slab structure and soft-supported weak-slab structure is analyzed, and the type of uniform load and calculation model of concrete thin-slab false roof are improved. Finally, according to the established mechanical model of thin slab false roof, finite element analysis and field application were carried out. The results show that there are three types of deflection curve differential equations in the concrete thin slab false roof perpendicular to the strike, and three extreme points exist in the middle section of the thin slab and on both sides of the surrounding rock. The hazardous surface of the hard-supported weak-slab structure is present at the intersection of the encircling rock and the thin-slab fake ceiling, with the perilous point situated on the top of this surface. The hazardous surface of the soft-supported weak-slab structure can be found in the centre section of the thin-slab fake ceiling, with the perilous point being located at the bottom of this surface. Moreover, the damage mode for both structures is that of maximum tensile stress damage. Upon conducting a finite element analysis, the results indicate that the concrete's maximum tensile stress is significantly high.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

There is a growing need to implement modern technologies, such as digital twinning, to improve the efficiency of transport fleet maintenance processes and maintain the company's operational capacity at the required level. Therefore, the paper reviews the existing literature to present an up-to-date and content-relevant analysis in this field. The proposed methodology is a systematic literature review using the Primo multi-search tool following Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. The main inclusion criteria included the publication dates (studies published from 2012–2024) and studies published in English. This resulted in the selection of 201 of the most relevant papers in the area of investigation. Finally, selected articles in this review were categorized into seven groups: a) air transportation, b) railway transportation, c) land transportation (road), d) in-house logistics, e) water and intermodal transportation, f) supply chain operation, and g) other applications. One of the main advantages of the study is that the results are obtained from different scientific sources/databases thanks to using the multi-search tool. Moreover, a bibliometric analysis of the selected papers was performed. The results have led the authors to specify the main research problems and trends related to the analyzed area and to identify the main research gaps for future investigation from academic and engineering perspectives. In addition, based on the review results, a framework for DT in transportation system maintenance was developed. The study ends with conclusions and future research directions.

The advancement of autonomous capabilities in maritime navigation has gained significant attention, with a trajectory moving from decision support systems to full autonomy. This push towards autonomy has led to extensive research focusing on collision avoidance, a critical aspect of safe navigation. Among the various possible approaches, Dynamic Programming is a promising tool for optimizing collision avoidance maneuvers. This paper presents a DP formulation for collision avoidance of autonomous vessels. We set up the problem framework, formulate it as a multi-stage decision process, define cost functions and constraints focusing on the actual requirements a marine maneuver must comply with, and propose a solution algorithm leveraging parallel computing. Additionally, we present a greedy approximation to reduce algorithm complexity. Through case studies, we demonstrate the effectiveness of the proposed approach in navigating complex scenarios, contributing to the future of autonomous maritime navigation. Through case studies, we show the efficacy of our approach in navigating complex scenarios.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

Aim: M. oleifera, a tree that have medicinal applications. A.hispidum has been utilized in traditional medicine as a cure for microbial and other infections. The aim of this study is to evaluate the bioactive compounds of A.hispidum and M.oleifera and determination of Antioxidant, Anticancer, Antifungal and Antibacterial for their pharmaceutical importance. Methods: Fresh leaves of these plants were collected from Akinmoorin and Awe in Nigeria. Particles Induced X-Ray Emission method was carried out via a 2.5MeV proton beam. Detection of phytochemicals was carried out by HPLC analysis. Disc diffusion method was used to determine MIC for fungi and MIC for bacteria. DPPH radical scavenging activity of these plant leaves was determined. Cancer cells were cultivated using 5% CO2 with 95% air in 100% relative humidity. The adherent cells were seeded and subjected to treatment with increase concentrations of the plant extracts from 48–72 h for anti-cancer activity. Results: The mean ± S.E. of the mean (S.E.M.) for all data were displayed. Three copies of the invitro experiment data were collected. For unpaired data, the student's t-test was applied at P < 0.05, the differences in the data were deemed significant. The ethanolic extracts showed on the average a 50% reduction in cancer cell viability at 24.5μg mL−1 for MO and 16.0μg mL−1 for AH respectively. Conclusions: The results of this study indicated these two plants have Antioxidant, Antitumor, Antifungal and Antibacterial activity and it is recommended that the active constituents be isolated and formulated into suitable dosage form. Keywords: Phytochemical Screening; pharmacological activities; Acanthospermum hispidum; Moringa oleifera.

It’s been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects on the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related-signaling pathways of treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-Tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, the MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results would provide novel insights into the treatment of immunosuppression in humans.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

Onions are an excellent source of a variety of essential antioxidants, polyphenols, and other phytonutrients. These onions were used to enhance the meal's flavour and aroma. Additionally, onions have long been recognised for their ability to change food texture, making it more pleasant for eating. Among the most significant phenolic compounds identified in onions was Quercetin, which has been proven to be very helpful for maintaining good health by reducing the risk of heart disease, cancer, and a number of other severe conditions. Polyphenol extraction is essential for the effective usage and research of these phytochemicals. Previously, the extraction process was complicated by a variety of traditional methods, but with the aid of contemporary technology, the procedure was simplified. Additionally, it was found that red onions had greater health benefits than yellow onions, which were the most commonly used kind at the time. Apart from their health benefits, polyphenols were well recognised for their industrial use in dyeing, polymer manufacturing, and resin synthesis.

The Fuzzy Transportation Problem (FTP) represents a significant extension of the Classical Transportation Problem (TP) by introducing uncertainly and imprecision into the parameters involved. Various algorithms have been proposed to solve the FTP, including fuzzy linear programming, metaheuristic algorithms and fuzzy mathematical programming techniques combined with Artificial Neural Networks. This paper presents the application of Trigonometric Acceleration Coefficients-PSO (TrigAc-PSO), a variation of the Classical Particle Swarm optimization algorithm, which is an innovative algorithm originally developed for solving the TP. TrigAC-PSO, has demonstrated remarkable success in optimizing various problem domains in crisp environments.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Recent advances in organoid technology have revolutionized cancer biology and thera-peutic interventions, offering personalized immunotherapy treatment. Organoids, three-dimensional cell cultures derived from patient tumors, accurately replicate the tumor microenvi-ronment, providing unprecedented insights into tumor-immune interactions and therapeutic re-sponses. In this literature-based study, we discuss various culture methods for the diverse appli-cations of organoids in cancer immunotherapy, including drug screening, personalized treatment strategies, and mechanistic studies. Additionally, we address the technological challenges asso-ciated with these methods and propose potential future solutions to accelerate the development of novel immunotherapeutic approaches. This review highlights the transformative potential of or-ganoid models in advancing preclinical cancer immunotherapy modeling, screening, and evalua-tion, paving the way for more effective and personalized cancer treatments.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Yoga promotes acceptance, compassion, physicality, active postures, mental and emotional awareness, and spiritual benefits. It involves breath techniques, postures, and body locks, maintaining balance and strength. It's based on ethical principles. Beyond simple performance, swimming is a catalyst for overall well-being. Complementarily, yoga serves as an invaluable adjunct for swimmers, enhancing flexibility, strength, and body awareness - a triad essential to aquatic excellence. The confluence of yoga and swimming, particularly through the practice of aqua yoga asanas, presents a new paradigm for both athletes and non-performers alike. Athletes who embrace the harmonious fusion of swimming and yoga unearth the potential for achieving not just athletic mastery but also a more balanced and fulfilling lifestyle. This blend provides a route not only to enhance performance in the water but also to elevate the overall quality of life. We examined the feasibility of incorporating yoga and swimming practice into Romanian subjects' lifestyles, designing a factor analysis in SmartPLS software, based on an online survey. The study assesses the participants' knowledge of yoga's theory and philosophy, as well as their perceptions of the swimming practice's benefits for social and health issues. According to our study, Romanian participants practice yoga and swimming as often as possible to reduce stress, improve concentration for work-related tasks, and improve joint elasticity, balance, and muscular tone. Thus, Yoga and swimming are substitutes for other approaches in prevention and therapy.