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.

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.

This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning, which allow prevention of neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuro-immuno-humoral pathway of transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, antioxidant and anti-inflammatory components, are also outlined. Based on the close interplay between the effects of ischemia, especially mediated by interaction of HIF factors and steroid hormones, the involvement of the hypothalamic-pituitary-adrenocortical system in remote ischemic conditioning is also discussed.

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.

In the early stage of new vehicle development, the requirements of maximum performance of the air conditioning (AC) system are obtained through Amesim software simulation, but the calibration control of the AC system is usually carried out in the prototype-build vehicle test stage, and the test time is spanned up to 10 months after spring (autumn), summer and winter, of which up to 2 months are for environment chamber tests. Due to the long calibration cycle of AC control in the road test, which seriously affects the vehicle launch time, virtual calibration technology of air conditioning system is developed to shorten the calibration cycle of AC systems and ensure the quality of vehicles. In the project development stage, the calibration control of the vehicle AC system can be realized to carry out the functional test of the AC system in advance. In that, the grade of maturity for the AC system control can be improved, the on-road calibration test cycle can be shortened, and the development cost can be saved.

The automotive industry is continuously seeking innovative solutions to improve the energy efficiency and sustainability of vehicles. Among the various energy-consuming systems in automobiles, air conditioning plays a crucial role. However, conventional vapour compression-based air conditioning systems are known for their high energy consumption and environmental impact. In recent years, adsorption technology has gained significant attention as a promising alternative due to its potential for higher energy efficiency and reduced greenhouse gas emissions. This review paper presents a comprehensive analysis of advancements in adsorption air conditioning technology specifically designed for automotive applications. The paper examines the recent research and development efforts in enhancing the performance and practicality of these systems, encompassing areas such as advanced materials selection, and system integration strategies. Furthermore, this review highlights the benefits and challenges associated with implementing adsorption air conditioning systems in vehicles. The environmental impact and potential for waste heat recovery are also discussed. Additionally, emerging trends, such as hybridization with conventional vapour compression systems, are explored to further optimize the energy efficiency and sustainability of automotive air conditioning. By critically evaluating the existing literature and research advancements, this review provides insights into the state-of-the-art thermally driven technologies for automotive applications.

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.

Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

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.

A new model predictive control (MPC) algorithm is used to select optimal air conditioning setpoints for a commercial office building, considering variable electricity prices, weather, occupancy and lighting. This algorithm, Cost-Comfort Particle Swarm Optimization (CCPSO), is the first to combine a realistic, smooth representation of occupants’ willingness to pay for thermal comfort with a bottom-up, non-linear model of the building and air conditioning system under control. We find that using a quadratic preference function for temperature can yield solutions that are both more comfortable and lower-cost than previous work that used a ``brick wall'' preference function with no preference for further cooling within an allowed temperature band and infinite aversion to going outside the allowed band. Using historical pricing data for a summer month in Chicago, CCPSO provided a 3\% reduction in costs vs. a ``brick-wall'' MPC approach with similar comfort and 13\% reduction in costs vs. a standard night setback strategy. CCPSO also reduced peak-hours demand by 3\% vs. the ``brick-wall'' strategy and 15\% vs. standard night-setback. At the same time, the CCPSO strategy increased off-peak energy consumption by 15\% vs. the ``brick-wall'' strategy. This may be valuable for power systems integrating large amounts of renewable power, which can otherwise become uneconomic due to saturation of demand during off-peak hours.

The increasing demand for water resources in urban areas, such as Bangladesh, due to population growth is a significant concern. One potential solution under consideration is the use of air conditioning (AC) condensate water. A study conducted at the European University of Bangladesh (EUB) focused on assessing the quality and quantity of AC condensate water from various systems. The results indicate that the collected water generally adhered to the quality standards established for drinking and household use in Bangladesh. Parameters such as pH (averaging 6.8), turbidity (1.08 NTU), total dissolved solids (TDS) (averaging 219 mg/L), iron content (0 mg/L), alkalinity (averaging 41.67 mg/L), arsenic (0 mg/L), chemical oxygen demand (COD) (averaging 3.67 mg/L), biochemical oxygen demand (BOD) (averaging 1.33 mg/L), chloride content (averaging 30.77 mg/L), and other factors were evaluated. Moreover, the AC units at EUB, varying in cooling capacity (1 ton, 2 tons, and 4 tons), produced substantial monthly volumes of 96, 177, and 354 liters of condensate water, respectively. This underscores the potential of AC condensate water as a valuable resource for addressing urban water scarcity. As a result, there is a pressing need for local decision-makers and policymakers to establish well-defined guidelines for the effective utilization of AC condensate water to mitigate water scarcity issues in urban areas.

The growing number of the accessed energy-efficient frequency conversion air conditioners is likely to generate a large number of harmonics on the power grid. The following shortage in the reactive power of peak load may trigger voltage collapse. Hence, this conflicts with people’s expectations for a cozy environment. Concerning the problems mentioned above, an active management scheme is put forward to balance the electricity use and the normal operation of air conditioning systems. To be specific, schemes to suppress the low voltage ride through (LVRT) and harmonic are designed firstly. Then to deaden the adverse effects caused by nonlinear group load running on the grid, and to prevent the unexpected accidents engendered from grid malfunction, the dynamic sensing information obtained by an online monitor is analyzed, which can be seen as an actively supervise mechanism. The combined application of active and passive filtering technology is studied as well. Thirdly, the new energy storage is accessed reliably to cope with peak-cutting or grid breaking emergencies, and the fuzzy control algorithm is researched. Finally, system feasibility is verified by functional modules co-operation simulation, and active management target is achieved under scientific and reasonable state-of-charge (SOC) management strategy.

A real-time two-way direct load control (TWDLC) of central air-conditioning chillers in wide area is proposed to provide demand response. The proposed TWDLC scheme is designed to optimize the load shedding ratio of every customer under control to ensure the target load to be shed is met at every scheduling period. In order to overcome the load reduction uncertainties of TWDLC, an innovative solution is proposed by applying a certain degree of loosening on the constraint of the actual shed load. Fuzzy linear programming is utilized to solve the optimization problem with fuzzy constraints. The proposed fuzzy linear programming problem is solved by delicately transforming it into a regular liner programming problem. A selection scheme used to obtain the feasible candidates set for load shedding at every sampling interval of TWDLC is also designed along with the fuzzy linear programming.

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.

Despite gender equality being present in the social and political sphere, we still encounter aspects that are characteristic of sexism. Such aspects impact upon gender inequality and different types of violence towards women. The present article aims to examine the behaviour of adolescents from Huelva with regards to ambivalent sexism towards women on social networks and their influence on health. Further, we seek to uncover adolescent’s perceptions with regards to gender differences in the use of social networks, the relationship between sexism and women's emotional well-being was observed. The study sample was formed by young people aged between 14 and 16 years who were residing in rural and urban zones in the south of Spain. A mixed methods approach was taken. At a quantitative level, a sample of 400 young people was recruited. These were administered a questionnaire about sexism which was composed of two scales and has been validated at a national and international level. At a qualitative level, the study counted on 33 young people who participated in in-depth discussions via interviews and discussion groups. The results showed that sexism emerges in adolescence in the analysed sample from the south of Spain. This favoured a digital gender gap and was reinforced through social networks such as Instagram and Snapchat. Rising awareness and a critical view of the aforementioned sexism was shown on the behalf of females, particularly those from urban backgrounds.

We review the state of dynamical downscaling with scale-constrained regional and global models. The methodology, in particular spectral nudging, has become a routine and well-researched tool for hindcasting climatologies of sub-synoptic atmospheric disturbances in coastal regions. At present, the spectrum of applications is expanding to other phenomena, but also to ocean dynamics and to extended forecasting. Also new diagnostic challenges are appearing such as spatial characteristics of small-scale phenomena such as Low Level Jets.

Microalloying of low carbon steel with niobium (Nb) and titanium (Ti) is standardly applied in high-strength low-alloy (HSLA) steels enabling austenite conditioning during thermo-mechanical controlled processing (TMCP), which results in pronounced grain refinement in the finished steel. The metallurgical effects of microalloying elements are related solute drag and precipitate particle pinning, both acting on the austenite grain boundary thereby delaying or suppressing recrystallization of the deformed grain. In that respect it is important to better understand the precipitation kinetics as well as the precipitation sequence in a typical Nb-Ti-microalloyed steel. Various characterization methods have been utilized in this study for tracing microalloy precipitation after simulating different austenite TMCP conditions in a Gleeble apparatus. Atom probe tomography (APT), scanning transmission electron microscopy in a focused ion beam equipped scanning electron microscope (STEM-on-FIB) and electrical resistivity measurements provide complementary information on the precipitation status and are correlated with each other. It will be demonstrated that accurate electrical resistivity measurements can monitor the general consumption of solute microalloys (Nb) during hot working which was complemented by APT measurements of the steel matrix. On the other hand, STEM revealed that a large part of Nb-containing particles during hot working are co-precipitated with titanium during cooling from the austenitizing temperature. Precipitates that form during cooling or isothermal holding can be distinguished from strain-induced precipitates by corroborating STEM measurements with APT results. APT specifically allows obtaining detailed information about the chemical composition of precipitates as well as the distribution of elements inside the particle. Electrical resistivity measurement, on the contrary, provides macroscopic information on the progress of precipitation and can be calibrated by APT. The current paper highlights the complementarity of these methods and shows first results within the framework of a larger study on strain-induced precipitation.

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

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

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

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.

This work presents a methodology for the generation and classification of phase resolved partial discharges (PRPD) patterns based on the use of a printed UHF monopole antenna and signal con-ditioning circuit to reduce hardware requirements. For this purpose, envelope detection technique was applied. In addition, test objects such as a hydrogenerator bar, dielectric disks with internal cavities in an oil cell, potential transformer, and tip-tip electrodes immersed in oil were used to generate partial discharge (PD) signals. To detect and classify partial discharges, the standard IEC 60270 (2000) method was used as reference. After acquisition of conditioned UHF signals, digital signal filtering threshold technique was used, and peaks of partial discharges envelopes pulses were extracted. Feature selection techniques were used to classify the discharges and choose the best features to train machine learning algorithms, such as multilayer perceptron, support vector ma-chine and decision tree. Accuracies greater than 84% were met, revealing the classification potential of the methodology proposed in this work.

Controlling the concentration of free radicals in polymerization systems is advantageous for preparing cationic polyacrylamide (CPAM) with high molecular weight and acceptable dissolvability. In this study, a novel ultraviolet (UV)-initiated system characterized with adjustable light intensity and redox-azo complex initiator was used to synthesize a CPAM flocculant named NP. Comparatively, another CPAM flocculant named SP with stable UV light intensity and single initiator was prepared. The chemical structure, morphology, and thermal stability were analyzed through instrumental analysis. Proton nuclear magnetic resonance indicated that NP was successfully prepared, and a small fraction of cationic homopolymer was mixed in the product. Polymerization conditions were optimized, and polymerization mechanism was determined by investigating the effects of various parameters on intrinsic viscosity, conversion, and dissolvability. Results showed that the best performance was obtained at indexes of 0.45 wt‰ redox initiator concentration, 0.2 wt‰ azo initiator concentration, 40.0 wt% of cationic monomer, first- and second-stage light intensities of 8.5 and 13 mW/cm², respectively, and 3 wt% urea. Sludge conditioning performances of NP and SP were comparatively evaluated, and the mechanism was determined by investigating the sedimentation behavior and floc size distribution. High intrinsic viscosity, porous morphology structure, and the mixed cationic homopolymer of NP resulted in better sludge conditioning performance.

The paper describes and analyzes the performance of a new thermoelectric generation system based on the use of Peltier cells inserted in the ducts of the air conditioning equipment. The hot and cold air streams that flow in the two separated sections of an air conditioning system are used to create a thermal gradient between the two faces of the Peltier cells. Hot and cold air flow inside the A/C unit are driven to a built in thermal chamber where the Peltier cells are placed. Peltier cells are incrusted into an insulation wall that separates the two sections of the chamber through which hot and cold air streams are flowing. The so designed configuration allows the Peltier cells to generate electric current. The study has been run for constant cold air temperature and variable hot air temperature, resulting in a variable performance of the thermoelectric generator. Theoretical study has been completed with experimental tests to determine real performance of the thermoelectric unit. Efficiency of the thermoelectric generator has been found to be linearly dependent on the temperature difference between hot and cold air subsections of the chamber. Maximum efficiency, however, is limited by the hot air stream temperature, since in real conditions ambient temperature cannot overpasses a specific value. For standard operational conditions, 5º C and 45º C for the cold and hot air streams, the thermoelectric generator operates at 44% of the maximum efficiency attainable.

Air conditioners are indispensable necessities in daily life and industrial production. However, the heat generation of their internal core power components can limit their performance release. In this work, we explore the application of thermoelectric coolers (TECs) in the field of power device heat dissipation through finite element simulation. First, we geometrically modeled the structure and typical operating conditions of core power devices in air conditioners. We compared the temperature fields in air cooling and TEC active cooling modes for high power consumption power devices in a 319 K operating environment. The simulation results show that in the single air cooling mode, the maximum temperature of the 173.8 W power device reaches 394.4 K and the average temperature reaches 373.9 K, which exceeds its rated operating temperature of 368.1 K. However, after adding TEC, the maximum temperature of the power device drops to 331.8 K at an operating current of 7.5 A and the average temperature of the device is 326.5 K. It indicates that TEC active cooling has a significant effect on the temperature control of the power device. At the same time, we also studied the effect of TEC working current on the temperature control effect of power devices. For TEC, there is a minimum working current of 5 A; when it is less than 5 A, TEC has no cooling effect; the cooling effect of TEC increases with an increase in working current. When the TEC working current is 10 A, the average temperature of the power device can be reduced to 292.9 K. This study has made a meaningful exploration of the application of TEC in chip temperature control and heat dissipation, providing a new solution for chip thermal management and accurate temperature control.

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.

Therapeutic measures aimed at optimising organ function prior to transplantation - whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal - have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a positive effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion in particular has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy, and therapeutic donor hypothermia in the intensive care unit after brain death confirmation have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to a favourable effect on graft survival in the long-term, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence on the basis of the large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Numerical simulations and experiments on evaporative condensers in air conditioning systems using R744 were performed. Two configurations were given to study the feasibility of operating the subcritical R744 cycle. It indicated the capable of evaporative cooling condensing R744 to liquify by analyzing the outlet temperature at the end of the condenser reached from 28.7oC to 30.3oC with the operating pressure from 72.6 bar to 68.5 bar. The mass flow rate in the study increases from 14.34 kg/h to 46.08 kg/h, the pressure drop also increases from 0.23 bar to 0.47 bar for the simulation and 0.4 bar to 0.5 bar for the experiment, respectively. This study indicates that a 5-layers of copper tubes configuration causes a higher pressure drop and lower COP when compared to an 8-layers of copper tubes that split into 2 sets for smaller pressure drop. In this study, the evaporative condensers using mini tubes that are flooded in the cooling water tank are suitable for the subcritical R744 air conditioning system. The results obtained from the experimental data are in good agreement with those obtained from the numerical results, with the deviation less than 5%.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

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.

Directed movement towards a target requires spatial working memory, including processing of sensory inputs and motivational drive. In a stimulus-driven, operant conditioning paradigm designed to train zebrafish, we present a pulse of light via LED’s and/or sounds via an underwater transducer. A webcam placed below a glass tank records fish swimming behavior. During operant conditioning, a fish must interrupt an infrared beam at one location to obtain a small food reward at the same or different location. A timing-gated interrupt activates robotic-arm and feeder stepper motors via custom software controlling a microprocessor (Arduino). “Ardulink”, a JAVA facility, implements Arduino-computer communication protocols. In this way, full automation of stimulus-conditioned directional swimming is achieved. Precise multi­day scheduling of training, including timing, location and intensity of stimulus parameters, and feeder control is accomplished via a user-friendly interface. Our training paradigm permits tracking of learning by monitoring, turning, location, response times and directional swimming of individual fish. This facilitates comparison of performance within and across a cohort of animals. We demonstrate the ability to train and test zebrafish using visual and auditory stimuli. Current methods used for associative conditioning often involve human intervention, which is labor intensive, stressful to animals, and introduces noise in the data. Our relatively simple yet flexible paradigm requires a simple apparatus and minimal human intervention. Our scheduling and control software and apparatus (NemoTrainer) can be used to screen neurologic drugs and test the effects of CRISPR­-based and optogenetic modification of neural circuits on sensation, locomotion, learning and memory.

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.

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

This study aimed to know the conditioning factors of the transition process to the self-care of women diagnosed with HIV/AIDS. This qualitative study was carried out from June to September 2015 with seven seropositive women, users of a specialized service in sexually transmitted diseases in the municipality of Imperatriz, Maranhão State, Brazil. For the data collection, an individual interview was used, and data analysis was performed by content analysis delineated by Hsieh and Shannon (2005). The resources that influence the self-care in the transition process of women with HIV/AIDS are represented by personal conditioning factors, such as the meaning they attribute to the living with the disease, personal attitudes and cultural beliefs, socioeconomic status, preparation and knowledge about the disease, and by conditioning factors found in the community and society. The transition theory can provide important insights about the resources present in the adaptation process of women diagnosed with HIV so that they can perform their self-care satisfactorily.

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.

In this paper, the experimental study of heating in 2 h lunch mode of air-conditioned bed system is carried out. The results show that the power consumption of heat conduction heating is only 0.34 kW·h, and the average heat dissipation is 81.3 W, while the power consumption of convection heating is 1.43 kW·h, with an average heat dissipation of 748.7 W. Regardless of power consumption or heat dissipation, convection heating is significantly higher than heat conduction heating, resulting in the room air temperature of the former increased from 12.3 °C to 17.3 °C, while the latter only increased from 14.4 °C to 15.2 °C. The study found that the water temperature of heat conduction heating can meet the thermal comfort needs of the human body in the range of 38~40 °C, while convection heating requires a higher temperature range, In contrast, the grade of hot water required for heat conduction heating is lower. Through the experiment, it is also found that the temperature of convection heating rises fast, but it is easy to appear dry feeling after a long time, while heat conductive heating has a slow temperature rise. there is a cool feeling within 20 min after the heating starts, and then the thermal comfort is better. The air conditioning system in this paper is used for the heating experiment in the winter lunch break mode, compared with convection heating, the overall thermal comfort of heat conduction heating is better and more energy efficient. it is suggested to adopt heat conduction heating mode in the winter heating of this system.

This study aimed to investigate the interactions between corn particle size (PS) and conditioning temperature (CT) on the performance, carcass traits, intestinal morphology, and immune responses in broilers fed a corn-soybean meal-based diet. A total of 360, one-day-old male broiler chicks (Ross 308) were randomly allocated into six dietary treatments in a 2×3 factorial arrangement, consisting of two corn PS (finely ground with geometric mean diameter (GMD) of 357 µm (PSF) vs. coarsely ground corn with GMD of 737 µm (PSC), and three CT [unconditioned (CTU), conditioned at 75◦C (CT75) and 90◦C (CT90)]. Birds accommodated in 30 pens with five replicates and 12 chicks per each. There was no interaction between corn PS and CT on growth performance and immune response of broilers at any growth phases. However, during the starter (0-10d) period, the average daily weight gain (ADWG) and feed conversion ratio (FCR) of PSF-fed birds were significantly improved compared to those fed PSC (P<0.05). During the starter (0-10d) and grower (11-24d) periods, increasing the conditioning temperature of corn increased the ADWG, while in the starter phase only the CT75 caused a lower FCR (P<0.05). Broilers fed PSF corn showed lowest FCR during the finisher (25-42d) period compared to those fed PSC (P<0.05). Conditioning corn at 75ºC reduced FCR during the finisher (25-42d) period compared to the birds fed CTU and CT90 corn (P<0.05). In whole experimental periods (1-42d), PSF and CT75 treatment increased the ADWG compared to the PSC and CTU (P<0.05). The CT75 treatment improved primary total anti-sheep red blood cell (SRBCs) titer (IgT) and IgM and secondary IgT and IgG responses compared to the other experimental groups (CTU and CT90) (P<0.05). No significant PS × CT interaction was found on Newcastle disease (ND) antibody titer of broiler chickens (P>0.05). Feeding CT75 corn reduced duodenum and jejunum relative length compared to the birds fed diets containing CTU corn. Significant PS×CT interactions (P<0.05) were observed for villus height, villus height to crypt depth, crypt depth, muscle thickness, and absorption surface area of jejunum. The highest carcass yield observed in PSF-CT75-group (P<0.05). In conclusion, the use of finely ground corn (PSF) conditioned at 75℃ (CT75) was beneficial to growth performance, development of the digestive tract, jejunum histomorphometry and the immune responses of broilers.

The hybridization of machine learning methods with soft computing techniques is an essential approach to improve the performance of the prediction models. Hybrid machine learning models, particularly, have gained popularity in the advancement of the high-performance control systems. Higher accuracy and better performance for prediction models of exergy destruction and energy consumption used in the control circuit of heating, ventilation, and air conditioning (HVAC) systems can be highly economical in the industrial scale to save energy. This research proposes two hybrid models of adaptive neuro-fuzzy inference system-particle swarm optimization (ANFIS-PSO), and adaptive neuro-fuzzy inference system-genetic algorithm (ANFIS-GA) for HVAC. The results are further compared with the single ANFIS model. The ANFIS-PSO model with the RMSE of 0.0065, MAE of 0.0028, and R² equal to 0.9999, with a minimum deviation of 0.0691 (KJ/s), outperforms the ANFIS-GA and single ANFIS models.

Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA based sequential conditioning with Venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to Venetoclax was observed. At day +30, 55 patients (90%) were in complete remission. Acute GvHD II°-IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The combination of sequential FLAMSA-RIC with Venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial has been initiated in 07/2023.

The paper aims to study the workflow of the detection center of stealthy attacks on industrial installations that generate increase in energy consumption while avoiding triggering fault detection and damaging the installation. Such long-lasting attacks on industrial facilities make production more expensive and less competitive. We present the concept of the remote detection system of cyberattacks directed at maliciously changing the controlled variable in an industrial process air conditioning system. The monitored signals are gathered at the PLC-controlled installation and sent to the remote detection system, where the discrepancies of signals are analyzed based on the Control Performance Assessment indices. The results of performed tests prove the legitimacy of the adopted approach.

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.

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.

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.

Interference fits are a very common shaft-hub connection due to their low manufacturing cost and excellent technical properties. Plastic Conditioning of this machine element is a new and not very well known method. By exploiting residual stresses and the associated increase in the yield point, these components can absorb operating loads such as rotating bending moments, torsion, temperature changes and centrifugal forces purely elastically and avoid plastic deformation during operation. Compared to conventionally joined interference fits, the load bearing capacity in the elastic range can be increased by almost 200% and a specifically defined additional safety against plastic deformation in the elastic-plastic range can be ensured. This paper examines the effects of Reverse Yielding on the technology of Plastic Conditioning of Interference Fits in Power Transmission Engineering. Based on the Shear Stress Hypothesis (SH), the Plane Stress State (PSS) and the ideal plastic behavior of materials, the stress-mechanical relationships are explained, the influencing parameters are examined and conclusions are drawn for the plastic conditioning process. Taking into account the theoretical knowledge according to the state of the art, modified material behavior assumptions (isotropic hardening) and the Von Mises Yield Criterion (VMYC) are also considered. In addition, the method of plastic conditioning of interference fits is introduced and its basic principles are briefly explained. Along with computational suggestions to avoid Reverse Yielding, open issues requiring further research are identified.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, antioxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review provides a comprehensive overview of the multifaceted biological activities exhibited by T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed encompassing its role in combating a broad spectrum of bacterial and fungal pathogens, respectively. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the antioxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. Overall, this review consolidates the existing knowledge on T-4-ol, providing a holistic understanding of its pharmacological abilities. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

Lippia javanica (Burm. f.) is a medicinal plant with multiple native uses in the treatment of colds, influenza, pneumonia, coughs, dermatitis, tuberculosis, asthma, and bronchial diseases. However, it remains underutilized in drug development. In this review, existing studies on the pharmacological activities of L. javanica, more specifically the antitumor, antiviral, and antibacterial properties as well as recent metabolites identified from the plant were appraised. Background information on the plant's ecological distribution, ethnobotanical importance, toxicity, and cytotoxicity activity was also provided. The information in the review was gathered from major scientific databases (Google scholar, BioMed Central, Scopus, PubMed, Springer, Web of Science, and Science Direct) using journals, conference proceedings, dissertations, books, and/or chapters. The review compiled 66 new metabolites from the plant while establishing the anticancer, antiviral, antibacterial, and other important pharmacological activities of the organic (most especially methanol and acetone) and aqueous extracts of various parts of the plant attributed to several secondary metabolites present in the volatile oil of the plant, which includes carvone, ipsdienone, limonene, linalool, myrcene, ocimenone, caryophyllene, piperitenone, sabinene, p-cymene, sabinene, myrcene, ipsenone, and tagetenone. While some of the metabolites of L. javanica have been linked through pharmacological studies to the various traditional uses of the plant, some others remain unexplored, emphasizing how underutilized the plant is in drug research and development. It is envisaged that the reports from this review will help to further encourage future research and guide further investigations into the pharmaceutical and medicinal uses of L. javanica.

For centuries, Foeniculi fructus (F. fructus) has been used as a traditional herbal medicine in China and Europe and is widely used as a natural therapy for digestive disorders, including indigestion, flatulence, and bloating. The mechanism by which F. fructus alleviates functional dyspepsia was analyzed through network pharmacology, and its therapeutic effect on an animal model of functional dyspepsia was investigated. The compounds, targets, and related diseases of F. fructus were studied utilizing the traditional Chinese medicine systems pharmacology (TCMSP) database. Information on the target genes was classified using the UniProt database. A network was built using Cytoscape 3.9.1, and functional dyspepsia-related genes were checked using the Cytoscape string application. The efficacy of F. fructus on functional dyspepsia, including gastroparesis and gastrointestinal motility, was confirmed by treatment with its extract in a mouse model of loperamide-induced functional dyspepsia. Seven compounds targeted twelve functional dyspepsia-associated genes. In a functional dyspepsia mouse model, F. fructus significantly suppressed the symptoms when compared to that in the control group. Our animal studies showed that the mechanism of action of F. fructus is closely related to gastrointestinal motility. Based on animal experimental results, the results showed that F. fructus provides a potential means to treat functional dyspepsia, suggesting that its medical mechanism for functional dyspepsia can be described by the relationship between seven key compounds of F. fructus, including oleic acid and β-sitosterol, and 12 functional dyspepsia-related genes.

Pineapple weed (Matricaria discoidea DC.) is a widely spread plant in Europe and North America. In ethnomedicine, it is well known for its anti-inflammatory and spasmolytic activity. The aim of the research was to develop novel methods of M. discoidea herb complex processing for creating the essential oil and the dry extracts and to investigate their phytochemical composition. Moreo-ver, the molecular docking of main substances and in vivo their soporific and analgesic activity were studied. The essential oil and two dry extracts from M. discoidea were prepared. Total 16 phenolic compounds (7 flavonoids, 7 hydroxycinnamic, 2 phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil 9 main terpenoids were identified by gas chromatography (GC). We showed that the phenolics extraction from the present herb was successful by using 70% ethanol in a triple extraction and in the range of 1:14-1:16. The in-vivo studies with rodents showed analgesic activity of M. discoidea extracts and the improvements in the sleep of animals. The dry extracts of M. discoidea herb did not show any toxicity. The molecular docking showed the high probability of COX-1,2 inhibition and NMDA receptor antagonism induced by the extracts.

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.

Air conditioning system of electric vehicles has new change as the internal combustion engine is being replaced with electrified AC motor. With large amount of batteries installed at the bottom of frame, the conventional compressor which is belt-driven can be removed and another AC motor can play the role for air conditioning in electric vehicles. From this change, the system efficiency would be improved since it is possible to control the electrified compressor independently from traction system in contrast with the belt-driven compressor. As a result, by applying the electrified compressor for air conditioning system, the whole system can achieve better efficiency and longer driving distance, which is most important in electric vehicles. In this paper, 3-phase interior permanent magnet synchronous motor (IPMSM) was designed using lumped-parameter model and finite element method.

This paper evaluates norms and assesses the level of knowledge in air conditioning project management within the construction industry. A total of 25 questions were distributed to multiple candidates, who were filtered based on pre-established inclusion and exclusion criteria. Thirty-nine candidates were ultimately approved to participate in the survey. The questions were designed to address five hypotheses, with each set of five questions corresponding to one hypothesis. The results were obtained after pre-processing the data using Matlab software. The data was pre-processed using Matlab software, and the results were analyzed using the Delphi method. The analysis revealed that only two hypotheses were approved: No matter whether there are nationalized safety rules or not, the impact of data sciences and smart technologies, including air conditioning management systems, is critical for human life in the building business.

The purpose of this study was to assess if self-regulation of intensity based on rating of perceived exertion (RPE) is a reliable method to control the intensity of metabolic conditioning of functional-fitness session. In addition, the relationship between RPE and changes in heart rate and lactate responses was also analyzed. Eight male participants (age 28.1 ± 5.4 years; body mass 77.2 ± 4.4kg; VO₂max: 52.6 ± 4.6 mL·(kg·min)⁻¹) completed three randomly sessions (5 to 7 days apart) under different conditions: (1) all-out (ALL); (2) self-regulation of intensity based on a RPE of 6 (hard) on the Borg CR-10 scale (RPE6); and (3) a control session. Rate of perceived exertion, LAC and HR response were measured pre, during and immediately after the sessions. The RPE and LAC during the ALL-OUT sessions were higher (p ≤ 0.05) than the RPE6 and control sessions for all the analyzed time points during the sessions. Regarding HR, the 22 min area under the curve of HR during ALL-OUT and RPE6 sessions were significantly higher (p ≤ 0.05) than the control session. The average number of repetitions was lower (p ≤ 0.05) for the RPE6 session (190.5 ± 12.5 repetitions) when compared to the ALL session (214.4 ± 18.6 repetitions). There was a significant correlation between RPE and LAC (p = 0.001; r = 0.76; very large) and number of repetitions during the session (p = 0.026; r = 0.55; large). No correlation was observed between RPE and HR (p = 0.147; r = 0.380). These results indicate that self-regulation of intensity of effort based on RPE may be a useful tool to control exercise intensity during a metabolic conditioning session of functional-fitness.

German chamomile galenic preparations are used to treat mild skin diseases, inflammation and spasms, and they have also reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well-known in ethnomedicine. Since chamomile has shown to have some adverse effects, there is a need to develop new formulations, such as dry extracts, for the present herb. The aims of this study were (1) to develop a novel method for preparing essential oils and dry extracts from German chamomile flowers, (2) to reveal the phytochemical composition of such extracts, and (3) to verify the analgesic and soporific activity of extracts in vivo with a rodent animal model. Furthermore, our study aims to gain knowledge of the ethnomedical status of chamomile in the past and presence. Essential oils and dry extracts were successfully prepared from the tincture and aqueous extracts obtained after hydrodistillation and from a tincture powder. Total 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids and 2 phenolic acids), were found in the dry extracts by using UPLC-MS/MS. Total 9 main terpenoids were identified in the chamomile oil, and these terpenoids represent the chemotype rich in bisabolol oxides A and B. In the highest yield, the ratio of phenolic compounds and extract was in the range of 1:14-1:16 and triple extraction was performed. In in-vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative effect in rodents was found with the extract prepared by using a 70% aqueous ethanol solution for extraction. The administration of such extract at the dose of 50 mg/kg significantly prolonged the sleeping time in rats.

The best form of prevention against human infection through bacteria, viruses and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. As a therapeutic measure, various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against covid-19 in particularly vulnerable clinical personnel. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in the "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.

Depression and obesity are highly comorbid with one another, with evidence for bidirectional causal links between each disorder and a shared biological basis. The available evidence suggests that genetic factors play a major role in influencing both the occurrence of comorbid depression and obesity, their courses, and their response to existing treatments. The current paper is a scoping review of studies that have evaluated the contribution of specific genetic variants to the comorbidity between obesity and depression. Based on a search of the PubMed and EMBASE databases, 28 studies were included in this review, covering 54 candidate genes. Positive associations were identified for fourteen genetic loci (AKR1C2, APOA5, COMT, DAT1, FTO, KCNE1, MAOA, MC4R, MCHR2, NPY2R, NR3C1, Ob, PCSK9 and TAL1). Replicated findings across two or more independent samples were observed for the FTO and MC4R genes. Many of these gene products represent novel molecular targets for the pharmacological management of obesity which are not pharmacologically influenced by existing anti-obesity or antidepressant medications. The implications of these associations for future drug development are discussed, with an emphasis on recent evidence on the polygenic architecture of comorbid depression and obesity, and on a precision medicine approach to these conditions.

The Kalanchoe genus is composed of more than 100 species that usually thrive in tropical environments, which have been used in folkloric medicine to treat various illnesses, including dermatological conditions. With this, the present study assesses the pharmacognostical and pharmacological properties of different species of the Kalanchoe genus as elements for a potential treatment for dermatological-related conditions, from findings of existing literature and studies. It was analyzed that the Kalanchoe pinnata plant, or one of the most common species of Kalanchoe, have been observed to have distinct morphological and microscopic characteristics. Further, it was discovered that different species of Kalanchoe have anti-inflammatory, antioxidant, antibacterial, and wound healing properties, which enable the plant to be used for dermatological products that are available to the market. With this, it is recommended that further studies be conducted in other understudied species of Kalanchoe regarding their pharmacological properties, as well as the use of other structures of the Kalanchoe plant for treatment of various dermatological conditions.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins, and Ca2+-linked transporters and voltage-gated channels. These findings suggest that pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss

The “memory of water” experiments suggested the existence of molecular-like effects without molecules. Although no convincing evidence of modifications of water – specific of biologically-active molecules – has been reported up to now, consistent changes of biological systems were nevertheless recorded. We propose an alternate explanation based on classical conditioning of the experimenter. Using a probabilistic model, we describe not only the biological system, but also the experimenter engaged in an elementary dose-response experiment. We assume that during conventional experiments involving genuine biologically-active molecules, the experimenter is involuntarily conditioned to expect a pattern, namely a relationship between descriptions (or “labels”) of experimental conditions and corresponding biological system states. The model predicts that the conditioned experimenter could continue to record the learned pattern even in the absence of the initial cause, namely the biologically-active molecules. The phenomenon is self-sustained because the observation of the expected pattern reinforces the initial conditioning. A necessary requirement is the use of a system submitted to random fluctuations with autocorrelated successive states (no forced return to the initial position). The relationship recorded by the conditioned experimenter is, however, not causal in this model because blind experiments with an “outside” supervisor lead to a loss of correlations (i.e., system states randomly associated to “labels”). In conclusion, this psychophysical model allows explaining the results of “memory of water” experiments without referring to water or another local cause. It could be extended to other scientific fields in biology, medicine and psychology when suspecting an experimenter effect.

International literature data report that the increase of infectious risk may be due to heating, ventilation and air conditioning (HVAC) systems contaminated by airborne pathogens. Moreover, the presence of complex rotating dehumidification wheels (RDWs) may complicate the cleaning and disinfection procedures of the HVAC systems. We evaluated the efficacy of a disinfection strategy applied to the RDW of two hospitals HVAC systems. Hospitals have 4 RDW systems related to the surgical areas (SA1 and SA2) and to the intensive and sub-intensive cares (IC and sIC). Microbiological air and surfaces analysis were performed in HVAC systems, before and after the disinfection treatment. Hydrogen peroxide (12%) with silver ions (10 mg/L) was aerosolized in all the air sampling points, located close to the RDW device. After the air disinfection procedure, reductions of total microbial counts at 22°C and fungi were achieved in SA2 and IC HVAC systems. An Aspergillus fumigatus contamination (6 CFU/500L), detected in one air sample collected in the IC HVAC system, was eradicated after the disinfection. Surface samples proved a good microbiological quality. Results suggest the need of a disinfection procedure aimed to improve the microbiological quality of the complex HVAC systems, mostly in surgical and intensive care areas.

Nowadays, an analysis of virtual media to predict society’s reaction to any events or processes is a task of great relevance. Especially it concerns meaningful information on healthcare problems. Internet sources contain a large amount of pharmacologically meaningful information useful for pharmacovigilance purposes and repurposing drug use. An analysis of such a scale of information demands developing the methods that require the creation of a corpus with labeled relations among entities. Before, there have been no such Russian language datasets. This paper considers the first Russian language dataset where labeled entity pairs are divided into multiple contexts within a single text (by used drugs, by different users, by the cases of use, etc.), and a method based on the XLM-RoBERTa language model, previously trained on medical texts to evaluate the state-of-the-art accuracy for the task of indication of the four types of relationships among entities: ADR–Drugname, Drugname–Diseasename, Drugname–SourceInfoDrug, Diseasename–Indication. As shown based on the presented dataset from the Russian Drug Review Corpus, the developed method achieves the F1-score of 81.2% (obtained using cross-validation and averaged for the four types of relationships), which is 7.8% higher than the basic classifiers.

Buprenorphine, an analogue of thebaine, is a Schedule III opioid in the United States used for opioid-use disorder and as an analgesic. Research has shown drugs like buprenorphine have a complicated pharmacology with characteristics that challenge traditional definitions of terms like agonist, antagonist, and efficacy. Buprenorphine has a high affinity for the mu (MOR), delta (DOR), kappa (KOR), and intermediate for the nociceptin opioid receptors (NOR). Buprenorphine is generally described as a partial MOR agonist with limited activity and decreased response at the mu-receptor relative to full agonists. In opioid naïve patients, the drug’s analgesic efficacy is equivalent to a full MOR agonist, despite decreased receptor occupancy and the “ceiling effect” produced from larger doses. Some argue buprenorphine’s effects depend on the endpoint measured, as it functions as a partial agonist for respiratory depression, but a full-agonist for pain. Buprenorphine’s active metabolite, norbuprenorphine, attenuates buprenorphine's analgesic effects due to NOR binding and respiratory depressant effects. The method of administration impacts efficacy and tolerance when administered for analgesia. There have been eleven-thousand reports involving buprenorphine and minors (age < 19) to US poison control centers, the preponderance (89.2%) with children. The consequences of prenatal buprenorphine exposure in experimental animals and humans should continue to be carefully evaluated. In conclusion, buprenorphine’s characterization as only a partial mu-agonist is an oversimplification. Contemporary research shows the traditional explanation of the pharmacology of buprenorphine does not take into account changes to receptor theory, pharmacological terminology, route of administration, and biologically active major metabolites.

Geijera Schott is a plant genus of the Rutaceae Juss. (rue and citrus) family, comprising six species which are all native to Oceania. Of the plants belonging to this genus, the most significant species that has a customary use is Geijera parviflora, which was used by Indigenous Australians, primarily as a pain reliever. Herein, a comprehensive review of the literature published on the genus Geijera from 1930-2023 was conducted. This is the first review for this plant genus and it highlights the chemical constituents reported to date, together with the range of pharmacological properties described from the various species and different parts of the plant. These properties include anti-inflammatory, anti-microbial, anti-parasitic, insect repellent, analgesic, neuroactive, and anti-cancer activities. Finally, a reflection on some of the important areas for future focused studies of this plant genus is provided.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

The liver performs a fundamental role in the regulation of diverse physiological processes. Despite enormous advances in modern medicine, there are no completely effective drugs that stimulate hepatic function, offer complete protection to the organ, or aid in regenerating hepatic cells. Thus, it is necessary to identify alternative plant-origin pharmaceuticals more effective and less toxic for the treatment of hepatic diseases. The aim of this research was to establish the chemical composition of the American cranberry (Oxycoccus macrocarpus) leaves extract and its aminoacids preparations as well as their hepatoprotective activity. 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 2 catechins, and 3 hydroxycinnamic acids) and main amino acids (valine, arginine, glycine, histidine, aspartic acid, and taurine) were identified and quantified in the American cranberry (O. macrocarpus) leaves extract and its 7 aminoacids preparations. The therapeutic and prophylactic consumption of the American cranberry leaves extracts led to a decrease in the intensity of the lipid peroxidation process compared to the control pathology group in the experiment of acute toxic damage to the liver by tetrachloromethane on rats. The most pronounced hepatoprotective activity was established for the American cranberry leaves extracts’ preparations with arginine and valine.

Copper, the highly toxicity micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1, a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes. DMT1 cannot be a donor of catalytic copper because it does not have cytosol domain which is required for copper transfer to the Cu-chaperons and following to cuproenzymes. Here we assume that DMT1 can mediate copper way required for regulatory copper pool. To verify this thought, we used CRISPR/Cas9 to generate H1299 cell line with CTR1 or DMT1 single knockout (KO) and CTR1/DMT1 double knockout (DKO). To confirm KOs of the genes qRT-PCR were used. Two independent clones for each gene were selected for further studies. In CTR1-KO cells, expression of the DMT1 gene was significantly increased. In subcellular compartments, copper concentration decreased dramatically in DKO cells. CTR1-KO cells, but not DMT1-KO, demonstrated reduced sensitivity to cisplatin and silver ions, agents that enter the cell through CTR1. The expression of genes, whose protein products require copper: HIF1α, XIAP, COMMD1, CCS, Cp, but not SOD1 and NF-kB, changed their level. Perhaps these data will help to understand how the disturbances of copper homeodynamics lead to the development of neurodegenerative and oncological disorders. Possibility of using CTR1 KO and DMT1 KO cells to study homeodynamics of catalytic and signaling copper selectively is discussed.