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.

Carotenoids are essential pigments that play a vital role in the photosynthetic process of algae and are important for human health and nutrition. Despite their potential value, algal carotenoids are being neglected by biofuel industries. Recent research is aimed at producing microalgal lipids and carotenoids simultaneously under abiotic stresses. In this study, the effect of different abiotic stress factors such as Nitrogen (N), Potassium (K), Phosphorous (P), Sulphur (S), light intensity, and photoperiod on biomass, lipid, and carotenoids synthesis in Monoraphidium sp. (MP) were explored utilizing a statistical method. In addition, 2, 7-dichlorofluorescein diacetate (DCF-DA) mediated spectrofluorimetry was employed to detect the ele-vation in ROS level. The results revealed that variations in nutrients and light con-ditions are the key factors in the up-regulation of biomolecules lipids and carote-noids in the algae. The carotenoids profiling was done by Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectroscopy (UPLC-Q-ToF-MS). Among consisting carotenoids violaxanthin, astaxanthin, and beta-carotene were enhanced by 1.3 folds, 1.19 folds, 1.08 folds, while lutein was declined by 1.32 folds under stressed condition compared to control. The identified carotenoids are rec-ognized for their importance in the pharmaceutical and nutraceutical industries, highlighting the significant role of MP in these sectors.

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 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.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Revealing the spatial distribution mechanism of the coupling effect between soil water and salt is essential for managing saline-alkali farmland. This study utilized the multifractal method to analyze soil water and salt under varying water content levels in arid saline-alkali farmland. Soil samples were collected on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after a rainfall event. The findings showed that a significant decrease in soil water content, contrasting with an increase in soil salt content throughout the soil layers post-rainfall. As water content decreased, the spatial variability of soil water initially increased from S1-3 and then decreased, while the spatial variability of soil salt decreased. The spatial distribution between soil water and salt exhibited a high correlation at S3-4 (with relative water content of soil ranging from 0.52 to 0.75) due to their coupling effect. However, soil salt was unevenly leached by rainfall at high water content levels (S1-2) and precipitated at low water content levels (S5), resulting in low spatial variability correlations between soil water and salt. This study elucidated the coupling process of soil water and salt, identifying their spatiotemporal distribution mechanism in dryland agricultural areas.

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.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Micro plasma devices (MPD) with power gains are of interest in applications involving operations in the presence of ionizing radiations, in propulsion, in control, amplification of high power electromagnetic waves, and in metamaterials for energy management. Here we review and discuss MPDs with an emphasis on new architectures that have evolved during the past 7 years. Devices with programmable impact ionization rates and programmable boundaries are developed to control the plasma ignition voltage and current to achieve power gain. Plasma devices with 1-10 μm gaps are shown to operate in the sub-Paschen regime in atmospheric pressures where ion-assisted field emission results in a breakdown voltage that linearly depends on the gap distance in contrast to the exponential dependence dictated by the Paschen curve. Small gap devices offer higher operation frequencies at low operation voltages with applications in metamaterial skins for energy management and in harsh environment inside nuclear reactors and in space. In addition to analog plasma devices, logic gates, digital circuits, and distributed amplifiers are also discussed.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

To better understand the shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology and properties has been carefully investigated. The results demonstrate that SMPU-OOBAm have liquid crystalline properties, triple-shape memory properties and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm shows triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm shows self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties and self-healing properties make the SMPU-OOBAm composites with many promise applications in smart optical devices, smart electronic devices and smart sensors.

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.

While numerous studies have explored the correlation between the built environment and ride-hailing demand, few have assessed their nonlinear interplay. Utilizing ride-hailing order data and multi-source built environment data from Nanjing, China, this paper uses the machine learning method, eXtreme Gradient Boosting (XGBoost), combined with SHapley Additive exPlanations (SHAP) and Partial Dependence Plots (PDP) to investigate the impact of built environment factors on ride-hailing travel demand, including their non-linear and threshold effects. The findings reveal that dining facilities have the most significant impact, with a contribution rate of 30.75%, on predicting ride-hailing travel demand. Additionally, financial, corporate, and medical facilities also exert considerable influence. The built environment factors need to reach a certain threshold or within a certain range to maximize the impact of ride-hailing travel demand. population density, land use mix and distance to the subway station collectively influence ride-hailing demand. The results are helpful for TNCs to allocate network ride-hailing resources reasonably and effectively.

The influence of short term water absorption on the mechanical properties of halloysite nanotubes-multi layer graphene reinforced polyester hybrid nanocomposites has been investigated. The addition of nano-fillers significantly increased the flexural strength; tensile strength and impact strength in dry and wet conditions. After short term water exposure; the maximum microhardness; tensile; flexural and impact toughness values were observed at 0.1 wt% MLG. The microhardness increased up to 50.3%; tensile strength increased up to 40% and flexural strength increased up to 44%. Compared to dry samples; the fracture toughness and surface roughness of all types of produced nanocomposites were increased that may be attributed to plasticization effect. Scanning electron microscopy revealed that the main failure mechanism is caused by the weakening of nano-filler-matrix interface induced by water absorption. It was further observed that synergistic effects were not effective at concentration of 0.1 wt% to produce considerable improvement in mechanical properties of produced hybrid nanocomposites.

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.

This study investigates the effects of Zinc (4wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. The severe plastic deformation (equal channel angular pressing (ECAP)) has been done followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4wt.%Zn enhances the uniform distribution of β-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4wt.%Zn alloy exhibits optimal yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4wt.%Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

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.

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.

Many farms are replacing the lighting with light emitting diode (LED) bulbs because of the technological modernization. We aimed to investigate the effects of incandescent light (IL) and LED lighting on Cobb500 broiler chickens for six weeks. Production parameters (body weight, feed consumption, feed conversion ratio), calculated slaughter values (yield%, relative breast%, thigh%) and breast meat quality parameters (pH at 45 min and 24 h postmortem, color, drip loss, kitchen equipment losses, shear force, meat composition) were recorded. Non-stop recordings were used to analyze the behavior of the birds in several periods of the rearing. LED group was significantly better in body weigh parameter between week 1-5 and feed conversion ratio between week 2-3. The most significant difference in behavior was observed in the middle of the rearing period. The chickens in the LED group spent more eating time, drinking time, interacting, and resting less. There was no difference in the meat quality parameters, only shear force was significantly lower in the LED group (1781.95±0.33 g/s vs. 2098.82±0.42 g/s). Based on our results, LED lighting can bring positive changes in animal production efficiency, behavior, and important characteristics for meat consumers.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

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.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

Most research on colostrum quality and colostrum management focuses on maternal IgG transfer to the newborn calf. However, in addition to being a source of antibodies, colostrum has other components that influence passive immune transfer, nutrition, gut maturation, and thermoregulation. In this review, the constituents in the bovine colostrum, as well as their variation, are explored and it is discussed the biological role of colostrum on the newborn calf. Protein is the nutrient in higher concentration and fat is the nutrient with the most variation. There is a pronounced amplitude in the total solids content of colostrum, but the average concentration does not vary much between studies (24.7%). Bovine colostrum major components can vary with several factors, such as the region, season, breed, dry period length, and nutritional aspects of the dam. Bioactive components, cells, and microbiome variability are less understood, besides IgG. Regardless, they play crucial distinct roles in the physiological development of the newborn. However, a multi-interactive effect between these components, cells, and microorganisms is more likely to occur. Recently researched components in colostrum like miRNA, nucleo(t)sides, the milk fat globule membrane, oligosaccharides, minor proteins, and the microbiome are examples of promising interest areas of study.

Tinnitus is a common phantom auditory percept, believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in absence of any clinical hearing loss. Then, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise, normal hearing, but the results are not consistent across studies. Here, we aim to investigate those differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis, which was associated with tinnitus found in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Fibroin-chitosan composites, especially those containing nanohydroxyapatite, show potential for bone tissue regeneration. The physicochemical properties of these biocomposites depend on the compatibility between their components. In this study, the intermolecular interactions of fibroin and chitosan were analyzed using a molecular dynamics approach. Two types of systems were investigated: one containing acetic acid and the other containing calcium (Ca²⁺) and hydrogen phosphate (HPO₄²⁻) ions mimicking hydroxyapatite conditions. After obtaining the optimal equilibrium structures, the distributions of several types of interactions including hydrogen bonds, ionic contacts, and hydrophobic contacts along with the structural and energetical features were examined. The calculated binding energy values for the fibroin-chitosan complexes confirm their remarkable stability. The high affinity of fibroin for chitosan can be explained by the formation of a dense network of interactions between considered biopolymers. These interactions were found to be primarily hydrogen bonds and ionic contacts involving ALA, ARG, ASN, ASP, GLN, GLU, GLY, LEU, PRO, SER, THR, TYR, and VAL residues. As it was established, the complexation of fibroin with chitosan maintains the β-sheet conformation of the peptide. β-Sheet fragments in fibroin are involved in the formation of significant amount of hydrogen bonds and ionic contacts with chitosan.

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.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

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).

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.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

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

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

Cysteine and its derivatives, including H2S, can influence bacterial virulence and sensitivity to antibiotics. In minimal sulfate media, H2S is generated under stress to prevent excess cysteine and, together with incorporation into glutathione and export into the medium, is a mechanism of cysteine homeostasis. Here, we studied the features of cysteine homeostasis in LB medium, where the main source of sulfur is cystine, whose import can create excess cysteine inside cells. We used mutants in the mechanisms of cysteine homeostasis and a set of microbiological and biochemical methods, including real-time monitoring of sulfide and oxygen, determination of cysteine and glutathione, and expression of the Fur, OxyR, and SOS regulons genes. During normal growth, the parental strain generated H2S when switching respiration to another substrate. The mutations affected the onset time, intensity and duration of H2S production, cysteine and glutathione levels, bacterial growth and respiration rates, and induction of defense systems. Exposure to chloramphenicol and high doses of ciprofloxacin increased cysteine content and GSH synthesis. A high inverse relationship between log CFU/ml and bacterial growth rate before ciprofloxacin addition was revealed. The study points to the important role of maintaining cysteine homeostasis during normal growth and antibiotic exposure in LB medium.

Expansion tube is ideal energy absorber which dissipates kinetic energy through plastic deformation and friction. There is an urgent need to understand the influence of key parameter, e.g. semi angle, tube material, and friction coefficient, on the mechanical response and energy absorption characteristics of expansion tube. In the present work, the material properties of the tubes were tested under quasi-static loading condition, and the numerical simulations were carried out by using commercial software ABAQUS. Based on the validated finite element simulation, all the semi angle, tube material, and friction have significant effects on the energy absorption capacity of expansion tube. The expansion tube with high tensile stress of parent material have high energy absorption capacity, while the specific energy absorption is linear with the tensile stress/density of tube material. This work would give a guidance to the structural design and parent materials selection for expansion tubes.

Solar photovoltaic (PV) generation suffers from multiple serious issues, for example shading effects directly affect the performance of installed PV arrays. By studying these issues, it can play a key role in improving the limitations and performance of PV panels. The study of PV arrays under partial shading conditions is mentioned in many papers as a part of other studies and as an independent phenomenon. Therefore, it is essential to improve these studies and update them with new research and study this problem in detail to know how to limit the effects of partial shading irradiance conditions on PV arrays performances, including economical aspects. This paper proposes to study the effects of different partial shading irradiance conditions for a PV array in various configurations. The analysis is proved in detail through the simulation of the proposed PV array in the Matlab/Simulink environment. The obtained results show the performances of interconnected PV arrays under different partial shading irradiance and temperature conditions, including the solar array I-V and P-V characteristics. In addition, different PV array configurations with and without bypass and blocking protection diodes improve and minimize the effect of partial shading conditions and avoid the reductions in output power.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Partially state-owned firms are common in both developed and developing countries and contribute around 10% of the world's GDP. This has led to a rich literature exploring various aspects of competition between such “mixed”-ownership firms. This paper contributes to the existing literature by studying the effects of mixed ownership on the intensity of competition in oligopoly markets. Our findings indicate that state ownership exerts an anti-competitive influence, with a higher state ownership share resulting in less aggressive behavior by firms in the product market. This result implies that industries with a higher proportion of state ownership yield lower total surplus. Further, when considering factors such as taxes, soft budget constraints, and weak property rights, the anti-competitive effects of state ownership are accentuated.

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.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

This study aims to test a model linking destination image, perceived value, tourist satisfaction, and tourist loyalty. Based on a sample of 300 tourists travelling by car from the World Natural Heritage Site of Tianchi, China, a new model of destination image was explored and data were analysed using partial least squares structural equation modelling (PLS-SEM). The results show that perceived value and satisfaction are direct antecedents of destination loyalty. Above all, perceived value and tourist satisfaction mediate the relationship between destination image and loyalty. Finally, this study discusses the theoretical and management implications of the findings in order to boost the tourism industry in the context of car trips.

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven a promising method for fast SOM content estimation. However, soil physical properties significantly affect the sensitivity of satellite hyperspectral imaging to SOM, leading to poor generalization ability of the estimation model. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on the spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root mean squared height, RMSH), and soil bulk weight (SBW), a soil spectral correction strategy was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPD) exceeding 1.4 in almost all bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, root mean square error (RMSE) of 5.74 g/kg, and RPD of 1.68. The prediction accuracy, R2, RMSE, and RPD of the model after migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction strategy based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. The performance comparison highlighted the advantages of considering soil physical properties in regional-scale SOM prediction.

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.

Background/Objectives: PEMF therapy has gained significant attention due to its potential benefits in promoting tissue repair and improving overall well-being. Recent publications in the field of exercise physiology, showed that pulsed electromagnetic fields (PEMFs) enhanced the velocity and the quantity of muscle O2 available and the rate of muscle oxygen extraction and utilization, in semi-professional cyclists, during a heavy constant-load exercise. In this paper, we investigate the effect of stimulation on muscular activation, in sedentary young people, during a constant-load exercise, performed at moderate intensity. Methods: Nine male sedentary young people, partic-ipated in this study. The response of the muscle activity, was recorded by surface EMG and assessed measuring the root mean square (RMS) normalized to the peak of the maximum voluntary con-traction. Data were collected in the right vastus Medialis (RVM) and right Biceps Femoris (RBF) at the baseline (standstill sitting), on warm-up (unloaded cycling) and during 30 minutes of con-stant-load exercise, in two experimental conditions (PEMF ON vs PEMF OFF). Results: The mul-tivariate analysis of variance performed on RVM showed a significant effect of PEMF in both warmup and exercise, while on RBF showed a significant effect of PEMF and warmup. Conclusions: PEMF strongly enhanced the amplitude of muscle activity in young sedentary people. The increase in the amplitude of the muscular response may lead to a higher oxygen consumption and release.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

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.

Three kinds of inorganic alkali are introduced into tetraethylenepentamine (TPEA) and polyethyleneimine (PEI) modified MCM-41 as the CO2 adsorbents. FT-IR and TGA are used to characterize the surface groups and the thermal stability of adsorbents. Chemical titration method is used to measure the alkali amounts of adsorbents. Thermo-gravimetric analysis with 10%CO2/N2 as the simulated flue gas is used to test the CO2 adsorption performance of adsorbents. The results show that all three kinds of inorganic alkali containing adsorbents exhibit promoted CO2 adsorption capability than traditional TPEA and PEI modified samples. Ca(OH)2 and PEI modified samples exhibit the highest adsorption capacity and stable regeneration property. The introduction of inorganic alkali changes the chemical adsorption mechanism between CO2 and increases the effective alkali amounts due to its hydroxyl groups. The CO2 adsorption capacities have a linear dependence relation with the alkali amounts of adsorbents, indicating that alkali amount is a critical factor for novel adsorbents exploring.

Aim: To analysis the relationship between healthy adults right ventricular diameter (RVD) and geographical factors. Location: China’s 22 provinces, municipalities and autonomous regions. Methods: Using correlation analysis the relationship between RVD and nine geographic factors, build predictive models by factor analysis. Results: There is significant correlation between RVD and geographical factors, and the annual average temperature is most relevant geographical factors, a predictive model was built by factor analysis: Ŷ = 19.46 + 0.0007072X1 + 0.001034X2 -0.05412X3 -0.001405X4 -0.0006351X5 + 0.02903X6 + 0.01243X7 -0.01033X8 + 0.03816X9 ± 0.63. Then using Kriging interpolation interpolate the geographical distribution of Chinese healthy adult right ventricular diameter reference value in ArcGIS software. Main Conclusion: If geographic factors can be derived in anywhere of China, RVD can be calculated by the model, you can also get RVD from geographical distribution.

This work investigated the isothermal holding time dependence of the densification, microstructure, weight loss and tensile properties of Fe-Mn-Si powder compacts. Elemental Fe, Mn and Si powder mixtures with a nominal composition of Fe-28Mn-3Si (in weight percent) were ball milled for 5h and subsequently pressed under a uniaxial pressure of 400 MPa. The compacted Fe-Mn-Si powder mixtures were sintered at 1200 ℃ for 0, 1, 2 and 3 h, respectively. In general, the density, weight loss and tensile properties increased with the increase of isothermal holding time. A significant increase in density, weight loss and tensile properties occurred in the compacts isothermally holding for 1 h, as compared to those with no isothermal holding. However, further extension of isothermal holding time (2 and 3 h) only played a limited role in promoting the density and tensile properties. The weight loss of the sintered compacts was mianly caused by the sublimation of Mn in Mn depletion region on the surface layer of the sintered Fe-Mn-Si compacts. The length of the Mn depletion region increased as isothermal holding time increased. A single α-Fe phase was detected on the surface of all the sintered compacts, and the locations beyond the Mn depletion region were comprised of a dual dominant γ-austenite and minor ε-martensite.

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.

In this study, the causal-effect between carbon dioxide emissions and forestry production and trade was investigated in Ghana by employing a data spanning from 1961 to 2014 by using the VECM and ARDL model. Evidence of the long-run equilibrium relationship in the VECM shows that, a 1% increase in veneer sheet production reduces carbon dioxide emissions by 1.47% in the long-run. There was evidence of a bidirectional causality between carbon dioxide emissions and veneer sheet production, carbon dioxide emissions and wood charcoal production, and a unidirectional causality running from carbon dioxide emissions to wood fuel production and plywood production to carbon dioxide emissions. Evidence from the long-run equilibrium relationship in the ARDL model shows that; a 1% increase in plywood production will increase carbon dioxide emissions by 0.17% in the long-run, a 1% increase in sawnwood production will increase carbon dioxide emissions by 0.17% in the long-run, a 1% increase in wood charcoal production will increase carbon dioxide emissions by 0.36% in the long-run and a 1% increase in wood fuel production will increase carbon dioxide emissions by 0.37% in the long-run.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

In recent years the number of available chemical pesticides has been significantly reduced and there have been an urgent need for discovery of alternative to chemical pesticides products, as among others the natural zeolites (zeolitic rocks). We determined the mineralogical and chemical composition of a specific and continuous layers of zeolitic rock sample (ZeotP) from Petrota, Ev-ros, Greece and evaluated its oviposition deterrent effect for the olive fruit fly Bactrocera oleae (Diptera: Terphritidae). The tested natural zeolite contained 70 wt. % Clinoptilolite, 18 wt. % Amorphous material, 7 wt. % Feldspars, 4 wt. % Cristobalite and 1 wt. % Quartz. We tested the oviposition deterrent effect of ZeotP mixed or not with an emulsifier adjuvant NU-FILM-P® in water and applied on the surface of olive fruits. The ZeotP oviposition deterrent effect for the ol-ive fly was very high under a series of tested temperatures (17°C, 20°C, 25°C and 30°C) and RHs (23%, 33%, 55%, 75%, 94%). In addition, the ZeotP residual deterrent effect after equable water spraying was high and similar to the respective effect of a pyrethroid insecticide (Decis®). Our results may contribute to an effective control of the olive fruit fly using an alternative to chemical pesticides natural zeolite (zeolitic rocks) product.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

The objective of this study is to investigate the effect of the premixed ethanol ratio based on the same total heating value in-cylinder on the equivalence ratio distributions and the injected fuel droplet behavior in the cylinder of the RCCI engine. The spray simulation was conducted by dividing two-part. First, the spray validation simulations progressed to find the spray-influenced factor of the test injector. Next, the engine simulations were performed with the spray-influenced factor obtained from spray validation simulations to investigate the effect of the premixed ethanol ratio based on the same total heating value in-cylinder on the injected fuel atomization and the equivalence ratio distributions. The introduced total heating value was fixed at 595J based on the lower heating value of diesel 14mg. The heating value of the premixed ethanol ratio varied from 0% to 40% based on the same total heating value in-cylinder in steps of 10%. It was revealed that when the premixed ethanol ratio based on the same total heating value in-cylinder was increased, the spray tip penetration value was reduced from the time after 4deg of diesel injection start because of the short injection duration by the small amount of diesel fuel. The SMD value was also more enormous up to 32.58% with increasing the premixed ethanol ratio because of the low kinetic energy of the injected fuel by the short injection duration and the slow evaporation of the injected fuel by the low cylinder temperature.

Proteins have the ability to adsorb on the surface of materials, such as soft contact lenses (SCLs), and can affect the hydrophobicity, roughness and surface properties of the contact lenses (CLs), which, in turn, can influence the friction between the lenses and the ocular surface. Excessive friction between contact lenses and the ocular surface can lead to discomfort for the wearer and may cause irritation or inflammation of the cornea, better known as corneal ulcers (keratitis). Bovine serum albumin (BSA) is often used as a standard protein in biocompatibility testing of materials, including contact lenses. One standard commercial contact lenses was tested under lubricated conditions to access the coefficient of friction (CoF), being the contact lubricated with a tear like fluid (TLF) solution containing six different concentrations of BSA. In all cases, a good linearity of the results of the friction force was verified, so the first friction law can be applied to determine the value of the coefficient of friction. It was found that friction increases with increasing protein concentration.

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.