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Background Increased proinflammatory molecules are a main reason for severe symptoms in patients infected with SARS-CoV-2. This study evaluated mutations in the S gene of SARS-CoV-2 and the expression of hsa-miR-223-5p, interleukin 2 receptor α (IL-2Rα), and CCL16 chemokine in hospitalized SARS-CoV-2 infected patients. Design This is a cross-sectional study. Methods This study included 75 SARS-CoV-2-infected patients with severe symptoms and 75 age-sex-matched healthy controls. Real-time polymerase chain reaction techniques were used to evaluate the expression levels of hsa-miR-223-5p, IL-2Rα, and CCL16 chemokine. The Sanger technique was used to sequence the S gene of SARS-CoV-2 from positions 23,274 to 23,641. Results The relative expression of hsa-miR-223-5p was significantly increased whereas that of IL-2Rα was significantly decreased in the SARS-CoV-2 infected patients. Two mutations were found in the S gene of SARS-CoV-2 at positions 23,403 (p.Asp23403Gly) and 23,525 (p.His23525Tyr) of the S gene of SARS-CoV-2. Conclusion Increased hsa-miR-223-5p may be a main cause for the downregulation of IL-2Rα, which is a main developer of T-regulatory lymphocytes. The mutations in the S gene of SARS-CoV-2-infected patients may affect immune responses to the molecule and alter the avidity of virus–human cell interactions. [ABSTRACT FROM AUTHOR]

While the hydrogen molecular ion is the simplest molecule in nature and very well studied in all of its properties, it remains an interesting system to use for explorations of fundamental questions. One such question treated in this study relates to finding an optimal adiabatic representation of the physics, i.e., the best adiabatic description that minimizes the role of nonadiabatic effects. As a test case explored here in detail, we consider the ungerade symmetry of H 2 + , which is known to have a huge scattering length of order 750 Bohr radii, and an incredibly weakly bound excited state. We show that a hyperspherical adiabatic description does an excellent job of capturing the main physics. Our calculation yields a competitive scattering length and shows that nonadiabatic corrections are small and can even be adequately captured using the post-adiabatic theory of Klar and Fano. [ABSTRACT FROM AUTHOR]

The molecular approach of a spin model is constructed on the Bethe lattice (BL), and then it is examined in terms of exact recursion relations. Rather than assuming that each BL site is inhabited by a single spin, each site is occupied by two spin-1/2 atoms A and B, forming a molecule. Each molecule is considered to contain two spin-1/2 atoms, as well as q = 3 , 4 , or 6 nearest-neighbor molecules. In addition to the internal interactions between the atoms of each molecule, the molecules interact via their atoms in terms of bilinear interaction parameters J. Atoms of a molecule interact with J A i B i , while the molecules interact via their atoms in terms of J A i B i + 1 = J B i A i + 1 and J A i A i + 1 = J B i B i + 1 . After obtaining the magnetizations of each atom in the central molecule of the BL, the average magnetization of the molecule is determined. It is found that the model presents first-and second-order and random phase transitions. The model also displays tricritical, bicritical and end points, in addition to reentrant behavior for appropriate J values. [ABSTRACT FROM AUTHOR]

Abstract Obtaining a fine approximation of a black-box function is important for understanding and evaluating innovative materials. Active learning aims to improve the approximation of black-box functions with fewer training data. In this study, we investigate whether active learning based on uncertainty sampling enables the efficient approximation of black-box functions in regression tasks using various material databases. In cases where the inputs are provided uniformly and defined in a relatively low-dimensional space, the liquidus surfaces of the ternary systems are the focus. The results show that uncertainty-based active learning can produce a better black-box function with higher prediction accuracy than that by random sampling. Furthermore, in cases in which the inputs are distributed discretely and unbalanced in a high-dimensional feature space, datasets extracted from materials databases for inorganic materials, small molecules, and polymers are addressed, and uncertainty-based active learning is occasionally inefficient. Based on the dependency on the material descriptors, active learning tends to produce a better black-box functions than random sampling when the dimensions of the descriptor are small. The results indicate that active learning is occasionally inefficient in obtaining a better black-box function in materials science.

Obtaining a fine approximation of a black-box function is important for understanding and evaluating innovative materials. Active learning aims to improve the approximation of black-box functions with fewer training data. In this study, we investigate whether active learning based on uncertainty sampling enables the efficient approximation of black-box functions in regression tasks using various material databases. In cases where the inputs are provided uniformly and defined in a relatively low-dimensional space, the liquidus surfaces of the ternary systems are the focus. The results show that uncertainty-based active learning can produce a better black-box function with higher prediction accuracy than that by random sampling. Furthermore, in cases in which the inputs are distributed discretely and unbalanced in a high-dimensional feature space, datasets extracted from materials databases for inorganic materials, small molecules, and polymers are addressed, and uncertainty-based active learning is occasionally inefficient. Based on the dependency on the material descriptors, active learning tends to produce a better black-box functions than random sampling when the dimensions of the descriptor are small. The results indicate that active learning is occasionally inefficient in obtaining a better black-box function in materials science. [ABSTRACT FROM AUTHOR]

Background Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa , at infection sites. Objectives As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. Methods In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems. Results It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1β expression in lung bronchial epithelial cells. Conclusions There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature. [ABSTRACT FROM AUTHOR]

In this paper, we first give characterizations of weighted Besov spaces with variable exponents via Peetre's maximal functions. Then we obtain decomposition characterizations of these spaces by atom, molecule and wavelet. As an application, we obtain the boundedness of the pseudo-differential operators on these spaces. [ABSTRACT FROM AUTHOR]

Introduction: One of the primary tenets in pharmacotherapy is that the applied drug must reach the target tissue at therapeutic concentration. For many therapies intended to treat hearing disorders it has become apparent that we have failed to achieve this goal, contributing to poor outcomes in several important clinical trials. The crux of the delivery problem is that small lipophilic molecules pass with relative ease through membranous boundaries of the body. This initially seems advantageous when the drug is applied intratympanically, enabling entry into perilymph through the round window membrane. Unfortunately, the same property also allows the drug to pass through endothelial cells of blood capillaries, allowing it to be eliminated from perilymph. Drugs that are eliminated rapidly as they diffuse along the cochlear scalae will only treat basal high-frequency cochlear regions and will not reach therapeutic concentrations in the apical regions of the human cochlea. Methods: We have used the FluidSim program, a computer model of the inner ear fluids, to derive perilymph elimination properties for 15 molecules from published and archival data sets, which are compared with calculated molecular properties. Results: Smaller, lipophilic drugs are shown to be eliminated from perilymph more rapidly, with half-times as fast as 17 min, compared to larger, polar ones, with half-times as long as 1,304 min (21.7 h). Discussion: Based on their molecular properties’ drugs can be identified that distribute well along the cochlea when applied intratympanically. This excludes many drugs that have been used for, or are currently in development for, inner ear therapy. On the other hand, it opens a vast array of less-studied, larger molecules, many of which would be unsuitable for oral delivery (characterized as “not druglike”) but representing promising candidates for local inner ear therapy. In the earliest stages of consideration, drugs need to be selected based on the properties which govern their ability to reach the appropriate target site and not whether they are efficacious in small animals or have high potency in vitro. Confirmation that the selected drug is reaching the target site(s) in a large animal model should ideally precede expensive clinical trials. [ABSTRACT FROM AUTHOR]

This is the last one of three successive articles by the authors on matrix-weighted Besov-type and Triebel–Lizorkin-type spaces B ˙ p , q s , τ (W) and F ˙ p , q s , τ (W) . In this article, the authors establish the molecular and the wavelet characterizations of these spaces. Furthermore, as applications, the authors obtain the optimal boundedness of trace operators, pseudo-differential operators, and Calderón–Zygmund operators on these spaces. Due to the sharp boundedness of almost diagonal operators on their related sequence spaces obtained in the second article of this series, all results presented in this article improve their counterparts on matrix-weighted Besov and Triebel–Lizorkin spaces B ˙ p , q s (W) and F ˙ p , q s (W) . In particular, even when reverting to the boundedness of Calderón–Zygmund operators on unweighted Triebel–Lizorkin spaces F ˙ p , q s , these results are still better. [ABSTRACT FROM AUTHOR]

The time dynamics of charge accumulation at the electrochemical interface between graphene and water is important for supercapacitors, batteries, and chemical and biological sensors. By using impedance spectroscopy, we have found that measured capacitance (Cm) at this interface with the gate voltage Vgate ≈ 0.1 V follows approximate laws Cm~T1.2 and Cm~T0.11 (T is Vgate period) in frequency ranges (1000–50,000) Hz and (0.02–300) Hz, respectively. In the first range, this dependence demonstrates that the interfacial capacitance (Cint) is only partially charged during the charging period. The observed weaker frequency dependence of the measured capacitance (Cm) at frequencies below 300 Hz is primarily determined by the molecular relaxation of the double-layer capacitance (Cdl) and by the graphene quantum capacitance (Cq), and it also implies that Cint is mostly charged. We have also found a voltage dependence of Cm below 10 Hz, which is likely related to the voltage dependence of Cq. The observation of this effect only at low frequencies indicates that Cq relaxation time is much longer than is typical for electron processes, probably due to Dirac cone reconstruction from graphene electrons with increased effective mass as a result of their quasichemical bonding with interfacial molecular charges. [ABSTRACT FROM AUTHOR]

This article shows that the gas-phase entropy of molecules is proportional to the area of the molecules, with corrections for the different curvatures of the molecular surface. The ability to estimate gas-phase entropy by the area law also allows us to calculate molecular entropy faster and more accurately than currently popular methods of estimating molecular entropy with harmonic oscillator approximation. The speed and accuracy of our method will open up new possibilities for the explicit inclusion of entropy in various computational biology methods. [ABSTRACT FROM AUTHOR]

In the pathological process of Alzheimer's disease, neuronal cell death is closely related to the accumulation of reactive oxygen species. Our previous studies have found that oxidative stress can activate microtubule affinity-regulating kinases, resulting in elevated phosphorylation levels of tau protein specifically at the Ser262 residue in N1E-115 cells that have been subjected to exposure to hydrogen peroxide. This process may be one of the pathogenic mechanisms of Alzheimer's disease. Vitamin E is a fat-soluble, naturally occurring antioxidant that plays a crucial role in biological systems. This study aimed to examine the probable processes that contribute to the inhibiting effect on the abnormal phosphorylation of tau protein and the neuroprotective activity of a particular type of vitamin E, α-tocotrienol. The experimental analysis revealed that α-tocotrienol showed significant neuroprotective effects in the N1E-115 cell line. Our data further suggest that one of the mechanisms underlying the neuroprotective effects of α-tocotrienol may be through the inhibition of microtubule affinity-regulated kinase activation, which significantly reduces the oxidative stress-induced aberrant elevation of p-Tau (Ser262) levels. These results indicate that α-tocotrienol may represent an intriguing strategy for treating or preventing Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Depression is a multifactorial disease with unknown etiology affecting globally. It's the second most significant reason for infirmity in 2020, affecting about 50 million people worldwide, with 80% living in developing nations. Recently, a surge in depression research has been witnessed, resulting in a multitude of emerging techniques developed for prediction, evaluation, detection, classification, localization, and treatment. The main purpose of this study is to determine the volume of depression research conducted on different aspects such as genetics, proteins, hormones, oxidative stress, inflammation, mitochondrial dysfunction, and associations with other mental disorders like anxiety and stress using traditional and medical intelligence (medical with AI). In addition, it also designs a comprehensive survey on detection, treatment planning, and genetic predisposition, along with future recommendations. This work is designed through different methods, including a systematic mapping process, literature review, and network visualization. In addition, we also used VOSviewer software and some authentic databases such as Google Scholar, Scopus, PubMed, and Web of Science for data collection, analysis, and designing comprehensive picture of the study. We analyzed 60 articles related to medical intelligence, including 47 from machine learning with 513,767 subjects (mean ± SD = 10,931.212 ± 35,624.372) and 13 from deep learning with 37,917 subjects (mean ± SD = 3159.75 ± 6285.57). Additionally, we also found that stressors impact the brain's cognitive and autonomic functioning, resulting in increased production of catecholamine, decreased cholinergic and glucocorticoid activity, with increased cortisol. These factors lead to chronic inflammation and hinder the brain's normal functioning, leading to depression, anxiety, and cardiovascular disorders. In the brain, reactive oxygen species (ROS) production is increased by IL-6 stimulation and mitochondrial cytochrome c oxidase is inhibited by nitric oxide, a potent inhibitor. Proteins, lipids, oxidative phosphorylation enzymes, and mtDNA are further disposed to oxidative impairment in the mitochondria. Consequently, mitochondrial dysfunction exacerbates oxidative stress, impairs mitochondrial DNA (mtDNA) or deletions of mtDNA, increases intracellular Ca2+ levels, changes in fission/fusion and mitochondrial morphology, and lastly leads to neuronal death. This study highlights the multidisciplinary approaches to depression with different aspects using traditional and medical intelligence. It will open a new way for depression research through new emerging technologies. [ABSTRACT FROM AUTHOR]

A semiempirical molecular-orbital approach has been developed to calculate the dissociation energies of 57 second-row neutral and charged diatomic molecules. One-electron energies and wave functions were used. The 2s and 2p electrons have separate energies and separate values of Z2S and Z2P. Calculations were made with a CNDO/INDO FORTRAN programme modified to a level of approximation that is more similar to extended Hückel calculations than to either CNDO or INDO. The correlation between calculated and experimental dissociation energies was favourable with a relative standard deviation of 15%. Additionally, dipole moments for the molecules were calculated concurrently with the same parameters. The correlation between calculated and experimental dipole moments was favourable for seventeen molecules with a relative standard deviation of 19%. The correlation between calculated and experimental ionisation potentials for fourteen molecules was also favourable with a relative standard deviation of 11%. Also, a repulsion work function was formulated and used in this work between pairs of atoms. For 90% of the molecules studied, the maximum calculated dissociation energy occurred within ±0.1 Å of the experimental bond distance. The semiempirical methods used in the present work could be used for future studies of larger molecules, including organic molecules. [ABSTRACT FROM AUTHOR]

Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications. [ABSTRACT FROM AUTHOR]

Understanding the quantum coherence effects is crucial for their promising applications, such as engineering artificial photosynthesis, manipulating chemical reactions, and designing coherence‐based functional devices. Considering that a molecule is the smallest unit that can exist independently and maintain its physical and chemical properties, investigating the quantum coherence effects of molecules is of great significance in understanding their features. In this case, exploring quantum coherence effects in the interaction of light and molecules has been one of the leading topics. This review presents an overview of state‐of‐the‐art spectroscopic techniques and deep insights into molecular quantum coherence effects. It also offers prospects for future advancement. First, the history of development and origins of quantum coherence effects are briefly introduced in molecules. Then, the principle and exciting experimental progress of sophisticated techniques for investigating molecular quantum coherence effects are discussed. Late, molecular quantum coherence effects and their promising applications in various areas have been evaluated. Finally, the challenges and potential solutions are look ahead for studying the effects of quantum coherence on molecules. This review may offer some guidance to boost the understanding and employing the molecular quantum coherence effects. [ABSTRACT FROM AUTHOR]

IntroductionOne of the primary tenets in pharmacotherapy is that the applied drug must reach the target tissue at therapeutic concentration. For many therapies intended to treat hearing disorders it has become apparent that we have failed to achieve this goal, contributing to poor outcomes in several important clinical trials. The crux of the delivery problem is that small lipophilic molecules pass with relative ease through membranous boundaries of the body. This initially seems advantageous when the drug is applied intratympanically, enabling entry into perilymph through the round window membrane. Unfortunately, the same property also allows the drug to pass through endothelial cells of blood capillaries, allowing it to be eliminated from perilymph. Drugs that are eliminated rapidly as they diffuse along the cochlear scalae will only treat basal high-frequency cochlear regions and will not reach therapeutic concentrations in the apical regions of the human cochlea.MethodsWe have used the FluidSim program, a computer model of the inner ear fluids, to derive perilymph elimination properties for 15 molecules from published and archival data sets, which are compared with calculated molecular properties.ResultsSmaller, lipophilic drugs are shown to be eliminated from perilymph more rapidly, with half-times as fast as 17 min, compared to larger, polar ones, with half-times as long as 1,304 min (21.7 h).DiscussionBased on their molecular properties’ drugs can be identified that distribute well along the cochlea when applied intratympanically. This excludes many drugs that have been used for, or are currently in development for, inner ear therapy. On the other hand, it opens a vast array of less-studied, larger molecules, many of which would be unsuitable for oral delivery (characterized as “not druglike”) but representing promising candidates for local inner ear therapy. In the earliest stages of consideration, drugs need to be selected based on the properties which govern their ability to reach the appropriate target site and not whether they are efficacious in small animals or have high potency in vitro. Confirmation that the selected drug is reaching the target site(s) in a large animal model should ideally precede expensive clinical trials.

Abstract Depression is a multifactorial disease with unknown etiology affecting globally. It’s the second most significant reason for infirmity in 2020, affecting about 50 million people worldwide, with 80% living in developing nations. Recently, a surge in depression research has been witnessed, resulting in a multitude of emerging techniques developed for prediction, evaluation, detection, classification, localization, and treatment. The main purpose of this study is to determine the volume of depression research conducted on different aspects such as genetics, proteins, hormones, oxidative stress, inflammation, mitochondrial dysfunction, and associations with other mental disorders like anxiety and stress using traditional and medical intelligence (medical with AI). In addition, it also designs a comprehensive survey on detection, treatment planning, and genetic predisposition, along with future recommendations. This work is designed through different methods, including a systematic mapping process, literature review, and network visualization. In addition, we also used VOSviewer software and some authentic databases such as Google Scholar, Scopus, PubMed, and Web of Science for data collection, analysis, and designing comprehensive picture of the study. We analyzed 60 articles related to medical intelligence, including 47 from machine learning with 513,767 subjects (mean ± SD = 10,931.212 ± 35,624.372) and 13 from deep learning with 37,917 subjects (mean ± SD = 3159.75 ± 6285.57). Additionally, we also found that stressors impact the brain's cognitive and autonomic functioning, resulting in increased production of catecholamine, decreased cholinergic and glucocorticoid activity, with increased cortisol. These factors lead to chronic inflammation and hinder the brain's normal functioning, leading to depression, anxiety, and cardiovascular disorders. In the brain, reactive oxygen species (ROS) production is increased by IL-6 stimulation and mitochondrial cytochrome c oxidase is inhibited by nitric oxide, a potent inhibitor. Proteins, lipids, oxidative phosphorylation enzymes, and mtDNA are further disposed to oxidative impairment in the mitochondria. Consequently, mitochondrial dysfunction exacerbates oxidative stress, impairs mitochondrial DNA (mtDNA) or deletions of mtDNA, increases intracellular Ca2+ levels, changes in fission/fusion and mitochondrial morphology, and lastly leads to neuronal death. This study highlights the multidisciplinary approaches to depression with different aspects using traditional and medical intelligence. It will open a new way for depression research through new emerging technologies.

Sexual dimorphism of visceral pain has been documented in clinics and experimental animal models. Aside from hormones, emerging evidence suggests the sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and the American College of Gastroenterology (ACG), up to 25% of the population have visceral pain at any one time, and in the United States 10–15 percent of adults suffer from irritable bowel syndrome (IBS). Here we examine the preclinical and clinical evidence of sex differences in visceral pain focusing on IBS, other forms of bowel dysfunction and IBS-associated comorbidities. We summarize preclinical animal models that provide a means to investigate the underlying molecular mechanisms in the sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems, and the communication of gut microbiota and neural systems all contribute to sex-dependent nociception and nociplasticity in visceral painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism. [ABSTRACT FROM AUTHOR]

Hadron spectroscopy is revealed by observing heavy resonances. Among various explanations of the internal structure of these hadronic states, hadronic molecules play a unique role. For hadronic molecules, which are associated with meson–meson or meson–baryon interactions, the Λ cutoff is a significant factor in determining the composite states' binding energies and overall properties. The cutoff becomes important when it comes to the location of hadronic molecules' masses because it influences the predictions. From this perspective, in the light of cutoff dependency, heavy quark spin partners of near-threshold the χ c 0 (3 9 1 5) , χ c 1 (3 8 7 2) , P c (4 4 4 0) , and P c (4 4 5 7) resonances, which are considered as hadronic molecules, are examined. [ABSTRACT FROM AUTHOR]

Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy's evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer's immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigenrelated cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12. [ABSTRACT FROM AUTHOR]

Objectives Hemoglobin (Hb) Lepore and Hb anti-Lepore are infrequent fusion gene variants that result from nonhomologous crossovers during meiosis. Conventional molecular testing methods may face challenges in identifying these variants. During Hb analysis using capillary electrophoresis, we encountered 6 cases with unusual Hb variants. Our aim was to identify the alterations in their globin genes. Methods Gap-polymerase chain reaction (PCR), reverse dot-blot assay (RDB), Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-read single-molecule real-time (SMRT) sequencing were used to confirm the presence of globin gene alterations. Results The routine thalassemia gene test kit using the gap-PCR and RDB techniques did not detect common gene variations. Direct sequencing failed to identify any known or unknown globin gene alterations. The MLPA analysis, however, revealed the possible presence of α-globin gene triplications as well as 2 types of fusion gene alterations. Further analysis using long-read SMRT sequencing accurately identified 3 rare gene variations: αααanti-3.7, Hb Lepore-Boston-Washington, and Hb anti-Lepore P-India. Conclusions Conventional methods may overlook rare thalassemias or Hb variants. Long-read SMRT sequencing has the potential to identify breakpoints in fusion genes, demonstrating that it is a promising technique for detecting rare thalassemias. [ABSTRACT FROM AUTHOR]

Research and development (R&D) in the pharmaceutical sector traditionally operated with in closed, siloed institutional settings, driven by intellectual property rights concerns that viewed data sharing as a threat. However, the evolving scientific landscape demands a more collaborative approach involving external engagement and dynamic partnerships. To address this, a hybrid contractual framework combining smart contracts, non-fungible tokens (NFTs), and traditional licensing schemes is introduced. This framework was developed through an experimental pilot platform that adhered to FAIR data principles, allowing participants to store, find, and reuse data related to drug discovery. The platform utilizes blockchain technology to document real-world assets in an immutable digital ledger. Smart contracts and NFTs offer an open and global collaborative platform for advancing drug research assets, overcoming hurdles related to standardization, interoperability, and disclosure. This framework aims to reconcile the conflict between the demand for greater data sharing and the protection of rightsholder interests in pharmaceutical R&D. By providing mechanisms for resolving practical challenges, it facilitates further cooperation and innovation in the field. [ABSTRACT FROM AUTHOR]

Isoprene, a lipophilic and unstable compound with the chemical formula C5H8, is transported to plant chloroplasts via the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, which relies on photosynthesis. Although only about 20% of terrestrial plants can synthesize isoprene, those that emit it are more adaptable to oxidative and thermal stresses. To shed light on the still-elusive protective mechanism of isoprene, numerous investigations have been conducted. Isoprene has been shown to react with and quench various reactive oxygen species (ROS) such as singlet oxygen (1O2). Its reduced state and conjugated double bonds suggest that it functions as an antioxidant, although this has yet to be conclusively proven. Despite its low abundance relative to other molecules in plant tissues, recent research has explored several potential roles for isoprene including acting as a scavenger of ROS by serving as an antioxidant; strengthening cell membranes; modulating genomic, proteomic and metabolomic profiles; signaling stress responses among neighboring plants compared with other volatile organic compounds (VOCs); regulating metabolic fluxes of hormones produced through the MEP pathway; or even functioning as a free developmental hormone. Future prospective studies, such as identifying the specific receptors for VOCs along with transcription factors (TFs) and other regulatory proteins participating in the signaling pathways and also metabolomic, transcriptomic and physiological analyses could help in comprehending VOC-induced defense responses in plants under stress conditions. [ABSTRACT FROM AUTHOR]

Introduction E-cigarettes are becoming increasingly popular in Australia, especially amongst the younger population. The synthetic cooling molecules WS-3 and WS-23 have been identified in e-cigarette products from the United States and Europe. The extent of inclusion of these synthetic coolants in Australian e-liquids is unknown, particularly in newer disposable e-cigarettes. Aims and Methods E-cigarettes and e-liquids were purchased within Australia and anonymously donated by Australian users. Nicotine, WS-3, WS-23, and menthol were quantified in the e-liquids using gas chromatography-mass spectrometry (GC-MS). Results WS-23 and nicotine were detected in all of the disposable e-cigarettes with WS-23 often present in high concentrations. There was no correlation between cooling terms in the flavor name and the inclusion of cooling agents. Only three bottled e-liquids were found to contain WS-23 while none contained WS-3 above the limit of detection. Conclusions Synthetic coolants were a common addition in disposable e-cigarettes while rarely added to e-liquid bottle refills. Their inclusion in these products is reflective of trends observed in United States and European e-cigarette products. Implications The increase in synthetic cooling agents as components of e-liquids, particularly disposable e-cigarette devices, has been observed within Australian samples across a range of brands and flavors. WS-23 was present in every disposable e-cigarette analyzed in this study, often in relatively high concentrations. Its inhalational toxicology should be considered when evaluating the safety of these products. [ABSTRACT FROM AUTHOR]

Сhalcogenide crystals reveal a wide range of changes in chemical and physical properties under band gap light illumination. A majority of these properties are determined by the electronic structure. However, to date there are only a few theoretical articles on the electronic structure of the As4Se4 molecule and only two on the As4Se4 crystal. We have studied, for the first time, the geometric and electronic structure of the As4Se4 crystal versus the As4Se4 molecule in the framework of a periodic model by the DFT method within the same approximations. Equilibrium bond lengths and bond angles were calculated together with charge density differences, Mulliken, Lowdin and Bader charges, and also Mulliken overlap populations, and were compared for the crystal and the molecule. A character of chemical bonding in the As4Se4 crystal versus the As4Se4 molecule was analyzed. The bandstructure DFT calculations were carried out and demonstrated that the As4Se4 crystal is an indirect-gap semiconductor.

We consider the energy for the molecular graphs of antiviral agents like Hydroxychloroquine, Remdesivir and Chloroquine. These drugs play a vital role in the treatment of COVID-19. Let Ѓ1,Ѓ2 and Ѓ3 be the n-dimensional graphs of the molecular structures of antiviral agents Hydroxychloroquine, Chloroquine and Remdesivir, respectively. We define their energies as E′(Ѓ1)=∑|λi′|, E′(Ѓ2)=∑|λj′| and E′(Ѓ3)=∑|λk′|, respectively. Where the sets {λ1′(Ѓ1),λ2′(Ѓ1),λ3′(Ѓ1),...,λn′(Ѓ1)}, {λ1′(Ѓ2),λ2′(Ѓ2),λ3′(Ѓ2),...,λn′(Ѓ2)} and {λ1′(Ѓ3),λ2′(Ѓ3),λ3′(Ѓ3),...,λn′(Ѓ3)} depict the eigenvalues for the adjacency matrices of Ѓ1,Ѓ2 and Ѓ3, respectively. We have developed some basic ideas and properties in order to measure the energies for the antiviral agents Hydroxychloroquine, Chloroquine and Remdesivir.

Objectives The growing occurrence of bacterial resistance has spawned the development of novel antimicrobial agents. Antimicrobial peptides, a class of small molecules with antimicrobial activity, have been regarded as the ideal alternatives to antibiotics. Methods In this study, we amplified a new type of Zophobas atratus coleoptericin (denoted coleoptericin B) through rapid amplification of cDNA ends (RACE) PCR and expressed recombinant Z. atratus coleoptericin B (rZA-col B) by prokaryotic expression. Subsequently, we evaluated the antimicrobial effect and biocompatibility of rZA-col B in vivo , investigated its antimicrobial mechanism, and assessed its therapeutic effect in a murine model of mastitis caused by MDR Klebsiella pneumoniae. Results The in vivo studies demonstrated that rZA-col B possesses broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. It exhibited less than 1.5% haemolysis and 10% cytotoxicity, even at a concentration of 128 μM. Additionally, rZA-col B had a minimal risk of inducing drug resistance. Furthermore, rZA-col B could disrupt the integrity of bacterial membranes, induce membrane permeabilization and ultimately lead to bacterial death. Importantly, rZA-col B also alleviated mastitis caused by MDR K. pneumoniae in a murine model by enhancing bacterial clearance, reducing neutrophil infiltration, decreasing TNF-α and IL-1β expression, and protecting the mammary barrier. Conclusions rZA-col B may be a promising antibacterial agent to combat MDR bacterial infection. [ABSTRACT FROM AUTHOR]

Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histocompatibility complex (MHC) class I antigen-presentation to CD8 T cells in establishing cerebral malaria pathology, we developed novel H-2Kb LoxP and H-2Db LoxP mice crossed with Cdh5-Cre mice to achieve targeted deletion of discrete class I molecules, specifically from brain endothelium. This strategy allowed us to avoid off-target effects on iron homeostasis and class I-like molecules, which are known to perturb Plasmodium infection. This is the first endothelial-specific ablation of individual class-I molecules enabling us to interrogate these molecular interactions. In these studies, we interrogated human and mouse transcriptomics data to compare antigen presentation capacity during cerebral malaria. Using the Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we observed that H-2Kb and H-2Db class I molecules regulate distinct patterns of disease onset, CD8 T-cell infiltration, targeted cell death and regional blood–brain barrier disruption. Strikingly, ablation of either molecule from brain endothelial cells resulted in reduced CD8 T-cell activation, attenuated T-cell interaction with brain vasculature, lessened targeted cell death, preserved blood–brain barrier integrity and prevention of ECM and the death of the animal. We were able to show that these events were brain-specific through the use of parabiosis and created the novel technique of dual small animal MRI to simultaneously scan conjoined parabionts during infection. These data demonstrate that interactions of CD8 T cells with discrete MHC class I molecules on brain endothelium differentially regulate development of ECM neuropathology. Therefore, targeting MHC class I interactions therapeutically may hold potential for treatment of cases of severe malaria. [ABSTRACT FROM AUTHOR]

The encapsulation of molecules with different physicochemical properties (theophylline, blue dextran, salicylic acid and insulin) in whey protein (WP) and alginate (ALG) microparticles (MP) for oral administration was studied. MP based on WP/ALG were prepared by a cold gelation technique and coated with WP solution after reticulation. Molecules influenced polymer solution viscosity and elasticity, resulting in differences regarding encapsulation efficiency (from 23 to 100%), MP structure and swelling (>10%) and in terms of pH tested. Molecule release was due to diffusion and/or erosion of MP and was very dependent on the substance encapsulated. All the loaded MP were successfully coated, but variation in coating thickness (from 68 to 146 µm) and function of the molecules encapsulated resulted in differences in molecule release (5 to 80% in 1 h). Gel rheology modification, due to interactions between WP, ALG, calcium and other substances, was responsible for the highlighted differences. Measuring rheologic parameters before extrusion and reticulation appeared to be one of the most important aspects to study in order to successfully develop a vector with optimal biopharmaceutical properties. Our vector seems to be more appropriate for anionic high-molecular-weight substances, leading to high viscosity and elasticity and to MP enabling gastroresistance and controlled release of molecules at intestinal pH. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a common malignancy in women of reproductive age. Circular RNAs (circRNAs) are emerging players in OC progression. We investigated the function and mechanism of circular RNA hsa_circ_0027803 (circCDK17) in OC pathogenesis. Real‑time PCR (RT-qPCR) and western blot were utilized for gene and protein expression analysis, respectively. Cell counting kit‑8 (CCK-8), EdU and Transwell assays investigated OC cell proliferation, migration and invasion. The associations between circCDK17, miR-22-3p and CD147 were examined by dual-luciferase reporter and RNA-protein immunoprecipitation (RIP) assays. The in vivo model of OC nude mice was constructed to explore the role of circCDK17. CircCDK17 was increased in OC tissue and cells, and patients with higher expression of circCDK17 had a shorter survival. CircCDK17 downregulation inhibited OC cell proliferation, migration and invasion, and reduced epithelial-mesenchymal transition (EMT)-related markers. In vivo experiments showed that circCDK17 silencing inhibited OC tumor growth and metastasis. CircCDK17 depletion reduced CD147 level via sponging miR-22-3p. MiR-22-3p knockdown overturned effect of circCDK17 depletion on OC cell proliferation, migration and invasion. Meanwhile, overexpressed CD147 restored functions of circCDK17 downregulation on OC development. CircCDK17 is an important molecule that regulates OC pathogenic process through miR-22-3p/CD147. [ABSTRACT FROM AUTHOR]

Objective Gastric cancer (GC) is prevalent worldwide but has a dismal prognosis, and its molecular and pathogenic pathways remain unknown. Kallikrein 11 (KLK11) has a reduced expression in GC and may be a promising biomarker. Method Herein, the function of KLK11 in GC and its regulatory mechanism was studied. Gene sequencing and quantitative reverse transcription-polymerase chain reaction were used to determine the expression of KLK11 in GC and precancerous lesions. Cell function tests and flow cytometry were conducted to determine the proliferative capacity and cell cycle of GC cells, respectively. A luciferase reporter test confirmed the interaction between RNA molecules. The mTOR/4E-BP1 signaling pathway was analyzed using western blotting. Result KLK11 has a suppressed expression in GC samples. KLK11 decreased the proliferative capacity of GC cells, by inhibiting the degree of mTOR/4E-BP1 phosphorylation. In contrast, miR-1304 increased GC cell proliferation by inhibiting KLK11. Moreover, KLK11 was able to limit in vivo GC cell proliferation. Conclusion These findings reveal a promising strategy to prevent and treat GC by targeting the KLK11-mediated mTOR/4E-BP1 cascade. [ABSTRACT FROM AUTHOR]

The subfamily Scarabaeinae has been traditionally divided into tribes on the basis of morphological similarity between groups of genera or, even, dissimilarity shown by a single genus. Although various tribal units have been described over the past 220 years, they had been recently reduced to a maximum of only 12 through synonymies within some tribes. However, following the advent of morphological and molecular cladistic systematics, it is clear that there are many discrepancies between phylogeny and phenetic tribal classification. As a result the number of tribes has now been expanded to 20 by revalidating some tribes or describing new groupings although this revision is incomplete. Thus, this study provides a comprehensive review of the current status of dung beetle tribal classification with regards to validity in terms of monophyly versus polyphyly or paraphyly. We discuss the systematic position of tribes among Scarabaeinae and provide a summary of the generic and species structure for each tribe. Given the enduring polyphyly or paraphyly in several tribes, it is clear that further tribal units will need to be described or revalidated to resolve the discrepancies. Therefore, we discuss how to use multiple lines of evidence (molecular, morphological, biogeographical, and paleontological) to build the tree of life for dung beetles and consequently provide stability in the tribal classification of the lineage. [ABSTRACT FROM AUTHOR]

The article has a review on the viscosity models of liquids, starting with the viscosity models of past centuries, then models of viscosity of the ХХ century and, finally, the rheological models of the XX and XXI centuries. In the field of liquid rheology, there is no satisfactory quantitative theory that connects the rheological properties of the media with the parameters of their structure. The viscosity model of liquids is proposed, in which the liquid is considered as a system of non -current -appropriate molecules, immersed in a thermostat, which is the entire volume of fluid. Quantum transitions due to the interaction of molecules with a thermostat will be dissipative (with a probability Р), in contrast to interaction with an external (for example, electric) field (with probability F). Dissipative processes lead to the fact that the secondary field Z2 is always less than the primary Z1. Since the subsystem of molecules exchanges only energy with the thermostat, the corresponding ensemble of particles will be canonical. Theoretically calculated response function and a model is built. The fluid viscosity model that we proposed takes into account the thermodynamic properties of the liquid, its structure and response to external fields. [ABSTRACT FROM AUTHOR]

The article juxtaposes three paradigms of thinking about the present as a form of the current moment. The first, dialectical paradigm foregrounds alienation as a form of living in a world of social and political conflicts and antagonisms. The second, psychoanalytic paradigm projects categories of symptom and primal scene as components of the psychoanalytic meta-concept, namely the object. The third, multitudinal and virtual paradigm treats life forms in a material way, as components of culture disintegration and crystallization processes. [ABSTRACT FROM AUTHOR]

Light and colour are an inseparable pair that belongs equally to our everyday experiences and to the most controversial concepts of natural philosophical considerations. In chemistry teaching, an experiment‐based approach and a pragmatic interpretation of these terms is necessary that is compatible with the "big five" basic concepts of chemistry education. In this sense, the article presents a panorama of experiments, didactically reduced concepts and teaching/learning materials for teaching chemistry in lower and upper secondary schools. [ABSTRACT FROM AUTHOR]

In this article, the authors introduce matrix-weighted Besov spaces on a given space of homogeneous type, (X , d , μ) , in the sense of Coifman and Weiss and prove that matrix-weighted Besov spaces are independent of the choices of both approximations of the identity with exponential decay and spaces of distributions. Moreover, the authors establish the wavelet characterization of matrix-weighted Besov spaces, introduce almost diagonal operators on matrix-weighted Besov sequence spaces, and obtain their boundedness. Using this wavelet characterization and this boundedness of almost diagonal operators, the authors obtain the molecular characterization of matrix-weighted Besov spaces. As an application, the authors obtain the boundedness of Calderón–Zygmund operators on matrix-weighted Besov spaces. One novelty is that, by using the property of matrix weights and the boundedness of matrix-weighted Hardy–Littlewood maximal operators, all the proofs presented in this article are different from those on Euclidean spaces, the latter strongly rely on the fact that Schwartz functions on Euclidean spaces decay faster than any polynomial. Another novelty is that all the results of this article get rid of both the reverse doubling condition of the measure μ and the triangle inequality of the quasi-metric d under consideration, by fully using the geometrical properties of X expressed by dyadic reference points, dyadic cubes, and wavelets. Besides, all the results in this article are new even for Ahlfors regular spaces and RD-spaces. [ABSTRACT FROM AUTHOR]

This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group (P < 0.05), and the Beclin1 level was significantly higher than that in the infection model group (P < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group (P < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene mTOR of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.

Abstract Background Explainable artificial intelligence (XAI) methods have shown increasing applicability in chemistry. In this context, visualization techniques can highlight regions of a molecule to reveal their influence over a predicted property. For this purpose, some XAI techniques calculate attribution scores associated with tokens of SMILES strings or with atoms of a molecule. While an association of a score with an atom can be directly visually represented on a molecule diagram, scores computed for SMILES non-atom tokens cannot. For instance, a substring [N+] contains 3 non-atom tokens, i.e., [, $$+$$ + , and ], and their attributions, depending on the model, are not necessarily revealing an influence of the nitrogen atom over the predicted property; for that reason, it is not possible to represent the scores on a molecule diagram. Moreover, SMILES’s notation is complex, foregrounding the need for techniques to facilitate the analysis of explanations associated with their tokens. Results We propose XSMILES, an interactive visualization technique, to explore explainable artificial intelligence attributions scores and support the interpretation of SMILES. Users can input any type of score attributed to atom and non-atom tokens and visualize them on top of a 2D molecule diagram coordinated with a bar chart that represents a SMILES string. We demonstrate how attributions calculated for SMILES strings can be evaluated and better interpreted through interactivity with two use cases. Conclusions Data scientists can use XSMILES to understand their models’ behavior and compare multiple modeling approaches. The tool provides a set of parameters to adapt the visualization to users’ needs and it can be integrated into different platforms. We believe XSMILES can support data scientists to develop, improve, and communicate their models by making it easier to identify patterns and compare attributions through interactive exploratory visualization.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that leads to the massive loss of motor neurons in cerebrum, brain stem and spinal cord. It affects not only motor neurons but also other neurons and glial cells, resulting in the progressive muscle atrophy, the severe disability and the eventual death due to the respiratory failure. The pathogenesis of ALS is not fully understood. Currently, several factors are considered to be involved in the pathogenesis of ALS, such as genetic factors, imbalances in protein homeostasis, RNA metabolism disorders, mitochondrial dysfunctions, glutamate-mediated excitatory toxicities and intra-neuronal material transport disorders in neurons. The study of genetic mutations related to ALS pathogenesis will link the molecular and cellular mechanisms of the disease, thus enhancing the understanding of its occurrence and progression, thereby providing new insights for the pathogenesis of ALS. This review summarizes the current insights in the molecular genetic pathogenesis of ALS. [ABSTRACT FROM AUTHOR]

The ability to engineer sophisticated two-dimensional tessellation organic nanoarchitectures based on triangular molecules and on-surface-synthesized covalent multimers is investigated using scanning tunneling microscopy. 1,3,5-Tris(3,5-dibromophenyl)benzene molecules are deposited on high-temperature Au(111) surfaces to trigger Ullmann coupling. The self-assembly into a semi-regular rhombitrihexagonal tiling superstructure not only depends on the synthesis of the required covalent building blocks but also depends on their ratio. The organic tessellation nanoarchitecture is achieved when the molecules are deposited on a Au(111) surface at 145 ° C . This halogen-bonded structure is composed of triangular domains of intact molecules separated by rectangular rows of covalent dimers. The nearly hexagonal vertices are composed of covalent multimers. The experimental observations reveal that the perfect semi-regular rhombitrihexagonal tiling cannot be engineered because it requires, in addition to the dimers and intact molecules, the synthesis of covalent hexagons. This building block is only observed above 165 ° C and does not coexist with the other required organic buildings blocks. [ABSTRACT FROM AUTHOR]

A novel type of covalent organic frameworks has been developed by assembling definite cobalt‐nitrogen‐carbon configurations onto carbon nanotubes using linkers that have varying electronic effects. This innovative approach has resulted in an efficient electrocatalyst for oxygen reduction, which is understood by a combination of in situ spectroelectrochemistry and the bond order theorem. The strong interaction between the electron‐donating carbon nanotubes and the electron‐accepting linker mitigates the trend of charge loss at cobalt sites, while inducing the generation of high spin state. This enhances the adsorption strength and electron transfer between the cobalt center and reactants/intermediates, leading to an improved oxygen reduction capability. This work not only presents an effective strategy for developing efficient non‐noble metal electrocatalysts through reticular chemistry, but also provides valuable insights into regulating the electronic configuration and charge behavior of active sites in designing high‐performance electrocatalysts. [ABSTRACT FROM AUTHOR]

Let (X,ρ,μ)$({\mathcal {X}},\rho ,\mu)$ be a space of homogeneous type in the sense of Coifman and Weiss, and let Y(X)$Y({\mathcal {X}})$ be a ball quasi‐Banach function space on X${\mathcal {X}}$, which supports both a Fefferman–Stein vector‐valued maximal inequality and the boundedness of the powered Hardy–Littlewood maximal operator on its associate space. The authors first introduce the Hardy space HY∗(X)$H_{Y}^*({\mathcal {X}})$, associated with Y(X)$Y({\mathcal {X}})$, via the grand maximal function and then establish its various real‐variable characterizations, respectively, in terms of radial or nontangential maximal functions, atoms or finite atoms, and molecules. As an application, the authors give the dual space of HY∗(X)$H_{Y}^*({\mathcal {X}})$, which proves to be a ball Campanato‐type function space associated with Y(X)$Y({\mathcal {X}})$. All these results have a wide range of generality and, particularly, even when they are applied to variable Hardy spaces, the obtained results are also new. The major novelties of this paper exist in that, to escape both the reverse doubling condition of μ and the triangle inequality of ρ, the authors cleverly construct admissible sequences of balls and fully use the geometrical properties of X${\mathcal {X}}$ expressed by dyadic reference points or dyadic cubes and, to overcome the difficulty caused by the lack of the good dense subset of HY∗(X)$H_{Y}^*({\mathcal {X}})$, the authors further prove that Y(X)$Y({\mathcal {X}})$ can be embedded into the weighted Lebesgue space with certain special weight and then can fully use the known results of the weighted Lebesgue space. [ABSTRACT FROM AUTHOR]

Background & Aims: Controlling inflammatory factors after myocardial infarction (MI), due to the lack of sufficient myocardial blood flow, is one of the factors influencing the recovery of infarction patients. Therefore, it is very necessary to know the causes of MI as one of the main causes of death in worldwide. The disease affects nearly three million people global and kills more than one million people in the United States each year (1) and cardiovascular problems caused by MI are the most common cause of MI (2). Research has shown that adhesion molecules play an important role in the pathogenesis of MI. New markers of intercellular adhesion molecule (ICAM) and vascular adhesion molecule (VCAM) have high sensitivity and accuracy in predicting and identifying the risk of heart damage and play an important role in the Prevalence of heart problems (2). It seems that the reduction of inflammatory markers has a positive effect on improving the condition of MI patients (4). Also, finding appropriate training methods and different training intensities has been the focus of researchers in the field of exercise physiology in recent years. There are conflicting studies between endurance training and the expression of ICAM and VCAM genes (5, 6). Also considering that electrical stimulation (ES) is used as a new and effective modality in the treatment of ischemia (8). Therefore, it was used as another intervention in the present study. According to research, it is expected that ES is a rehabilitation method for people who participate in exercise training (10) and also patients with heart failure (HF) (11). However, in other studies, the positive effects of exercise and ES on various aspects of heart health in patients with MI have been noted. For that reason, the researchers of the present study intend to investigate the exercise rehabilitation response with electrical stimulation on serum ICAM and VCAM levels of rats with myocardial infarction. Methods: In this experimental study, 40 Wistar rats (8 weeks old with an average weight of 220 ± 30 g) were randomly divided into 4 infarction groups, infarctionexercise rehabilitation, infarction electrical stimulation and infarction-exercise rehabilitation-electrical stimulation groups were divided. Then, MI was induced using two subcutaneous injections of Isoproterenol (ISO) (150 mg/kg) with an interval of 24 hours in the infarcted groups. This substance is one of the common methods of inducing MI in animal models, especially rats (14). In this study, heart infarction was confirmed based on electrocardiographic changes (ST segment elevation) along with the increase of cardiac enzyme cTnI (344.01 pg/ml). The intervention groups underwent exercise rehabilitation (treadmill at a speed of 20 m/min for 1 hour) and ES (foot shock device for 0.5 mA and 20 minutes) for one session. Groups were anesthetized and killed immediately after the end of the training protocol with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg). Blood sampling was done directly from the right atrium of the rat. The serum levels of ICAM and VCAM were checked by ELISA method. After confirming the normal distribution of the data using the Shapiro-Wilk test, one-way ANOVA and Tukey's post hoc test were used to analyze the data at a significance level of P<0.05. Results: The results of the analysis of ICAM levels showed a statistically significant difference between MI and MI.ES groups (F=4.4 and P=0.021), MI.EX and MI.ES (F=5.9 and P=0.002). But this difference between MI with MI.EX (F=1.4 and P=0.762), MI with MI.EX.ES (F=1.17, P=0.838), MI.EX with MI.EX. ES (F=2.56, P=0.292) and MI.ES with MI.EX.ES (F=3.26, P=0.124) were not significant. The results of VCAM levels showed a statistically significant difference between MI and MI.ES groups (F=3.9 and P=0.040) and MI and MI.EX.ES groups (F=2.3 and P=0.038). But between the groups, MI with MI.EX (F=1.60 and P=0.659), MI.EX with MI.ES (F=2.4, P=0.343, MI.EX with MI.EX .ES (F=2.4, P=0.331) and MI.ES with MI.EX.ES (F=0.034, P=0.999), this difference was not significant. Conclusion: Deficiency in the function of cell adhesion molecules is one of the main causes of pathological progress in many diseases, including cardiovascular disorders. Therefore, investigating inflammatory pathways and cellular and molecular processes involved in it is very necessary. The cholinergic anti-inflammatory pathway consisting of the Vagus nerve and its transporter acetylcholine play an important role in regulating the inflammatory response. When the body is injured, the excitability of the Vagus nerve increases, which causes the release of acetylcholine from peripheral nerve endings. This process can inhibit the release of pro-inflammatory cytokines such as IL-1, TNF-a, IL-6 and IL-17 and lead to the reduction of heart damage. Also, ES can change the function of inflammatory cells at the molecular level, thereby preventing the spread of inflammation by affecting the number of immune cells as a mediator. In general, it seems that according to the results of the present study, it is still not possible to determine with certainty the direction and direction of the effect of acute sports rehabilitation and foot shock electrical stimulation on adhesive molecules, and it needs more study. [ABSTRACT FROM AUTHOR]

The maximal covering location problem refers to the problem of finding an optimal placement of given number of facilities to a network. The objective is to maximize the total demands of the covered population within some constraints. Several metaheuristic approaches were proposed to solve the problem as it is an NP hard problem. In this article, we have proposed a chemical reaction optimization (CRO)-based approach to solve MCLP. CRO is a metaheuristic based on population to solve optimization problems. We are proposing a method to solve MCLP by redesigning four fundamental operators of CRO. Sometimes the solutions get trapped into local maxima, so an additional repair operator is also designed to find optimal solutions. The proposed algorithm is tested for both small and large scales of instances of datasets, which include benchmark as well as random ones. The proposed method gives best percentage of coverage results in 91.60% of instances, and for the remaining 8.40% of instances it produces results with average error value 0.10% which is very close to the optimal value. Nevertheless, the proposed method performs very well in terms of computational time for all test instances (100%) on all datasets compared to state-of-the-art method (Atta_GA). Wilcoxon signed-rank test has been performed on the results of the proposed method to observe the statistical significance. For both real-world and random instances, the results of the statistical test are significant. [ABSTRACT FROM AUTHOR]

Let φ : R n × [ 0 , ∞) ⟶ [ 0 , ∞) be a Musielak–Orlicz function satisfying the uniformly Muckenhoupt condition and be of uniformly lower type p φ - and of uniformly upper type p φ + with 0 < p φ - ≤ p φ + < ∞ , and let q ∈ (0 , ∞ ] . In this article, the authors introduce the Musielak–Orlicz–Lorentz Hardy space H φ , q (R n) which, when q = ∞ , coincides with the known weak Musielak–Orlicz Hardy space W H φ (R n) . Then the authors establish both atomic and molecular characterizations of H φ , q (R n) . Applying these characterizations, the authors obtain the real interpolation and the boundedness of Calderón–Zygmund operators on H φ , q (R n) when q ∈ (0 , ∞) or from the Musielak–Orlicz Hardy space H φ (R n) to H φ , ∞ (R n) in the critical case. The ranges of all the exponents under consideration are the best possible admissible ones which particularly improve all the known corresponding results for W H φ (R n) via weakening the original assumption 0 < p φ - ≤ p φ + ≤ 1 to the full range 0 < p φ - ≤ p φ + < ∞ , and all the results when q ∈ (0 , ∞) are new. The main novelty of this article is that the authors skillfully use the corresponding results related to weighted Lebesgue spaces via their relations with Musielak–Orlicz spaces to overcome those essential difficulties caused by the deficiency of both the explicit quasi-norm expression of Musielak–Orlicz spaces and the boundedness of the Hardy–Littlewood maximal operator on associate spaces of Musielak–Orlicz spaces. [ABSTRACT FROM AUTHOR]