Nanopores with irregularities are promising tools for distinguishing nano-size objects by their shape, but the forces on the object that critically influence its axial and rotational movement are unclear. The physics of the situation was described using the Poisson-Nernst-Planck and Navier-Stokes equations. With uniformly charged object the axial Coulomb and dielectric pressure (which opposes it and is surprisingly important), control the object's axial movement and rotation. Even without external pressure the hydrodynamic pressure is significant (negative at its upper and positive at its lower surface), but its total value is almost zero. If the object is charged only on the upper surface the axial upper Coulomb pressure is near zero close to the center, but negative near its end (the pressure is zero at the lower surface). The total axial dielectric pressure, which is largely dominated by the pressure at the upper surface, is positive along the length of the object becoming pronounced near its end. The axial hydrodynamic pressure is negative and significant at the upper surface (zero at the lower surface), diminishes in value near the object's end, critically influencing its axial movement, which becomes much faster. At its end the axial dielectric pressure prevails, and controls its rotation.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

The Nanosecond Pulsed Electric Field (nsPEF) or Nano Pulsed Stimulation (NPS) is a cutting-edge technology that applies a series of high-voltage electric field pulses of extremely short duration, typically on the order of nanoseconds, to cells. This technique induces the formation of nanopores and activate ionic channels, thereby altering cellular activity. Recent simulations suggest that nsPEF also triggers a novel phenomenon, Protein-mediated Electroporation, whereby pores are formed through the voltage-sensing domain of ionic channels. In this study, we employed Molecular Dynamics simulations and machine learning techniques to investigate the Voltage Sensing Domain (VSD) of a cardiac channel under nsPEF stimulation. Specifically, we characterized VSD structures that form pores helping for the understanding of the physical chemistry underlying the defibrillation effect of nsPEF. Our analysis involved the clustering of 142 replicas simulated for 50 ns under the nsPEF stimulus. Subsequently, we identified the representative structures of each cluster and calculated the free energy between them. Our results demonstrate that although VSD structures are ubiquitous among ionic channels, they exhibit distinct responses to nsPEF stimuli. These findings have significant implications for the development of novel nsPEF-based therapies for cardiac diseases.

According to traditional Chinese medicine, Qi and Blood circulate through the human body via pathways known as 'channels and collaterals'. This process supports the normal function of internal organs and the whole body. Pathological conditions can be attributed to abnormal circulation of Qi and Blood, which results in excess or deficiency of organs and channels. Therapeutic methods used in traditional Chinese medicine restore the balance of Qi and Blood.Since acupuncture was introduced in Europe, discussion and debate about the nature of 'acupoints,' 'channels,' and 'collaterals' has continued. Currently, opposing views exist on this subject, ranging from complete denial of the existence of the channels to uncovering the previously unknown system of intra-tissue gaps and microscopic vessels. The author offers an original hypothesis that regards the theory of channels and collaterals as the description of the physiology and pathology of intercellular space and the theory of organs as a description of the physiology and pathology of cells.

A method for sequencing a protein from a codon sequence is proposed. An unfolded protein molecule is threaded through a nano-sized pore in an electrolytic cell carboxyl end first and held with a voltage such that only the first residue is exposed in the trans chamber of the cell. A tRNA molecule in trans with matching anticodon for the residue binds itself to the latter in the presence of suitable catalysts. It is then cleaved and transferred to an extended electrolytic cell with N pores, 40 ≤ N ≤ 61, in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is held exposed in the trans chamber. In the presence of suitable catalysts the anticodon in the transferred tRNA binds with the codon of a matching RNA molecule. By reversing the voltages in the extended cell every RNA molecule except the one to which the transferred tRNA is bound retracts into its cis chamber, this identifies the residue unambiguously. The detected residue in the first cell is cleaved and the process repeated. Unlike in other nanopore-based methods, it suffices to detect the occurrence of a current blockade without having to measure the pore current precisely. A simplified but more time-consuming version that uses only the first cell is also described. In either case no a priori information about the protein is needed so de novo sequencing is possible. A feasibility analysis of the proposed scheme is presented.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular (CVD) disease not only due to multiple shared pathologic elements, but also because changes that develop over decades in CVD disease appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol, however, cholesterol dependent signaling such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase is downregulated indicating a cholesterol deficit with upregulation of cholesterol synthesis and efflux. Hypoxia related signaling in preeclampsia also appears paradoxical with increased Hypoxia Inducible Factors (HIF) in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol dependent signaling may arise from the effects of dietary lipid variance causing the cellular hypoxia which characterizes preeclampsia.

Nanoporous membranes promise energy-efficient water desalination. Hexagonal boron nitride (h-BN), like graphene, exhibits outstanding physical and chemical properties, making it a promising candidate for water treatment. We employed Car–Parrinello molecular dynamics simulations to establish accurate modeling of Na+ and Cl- permeation through hydrogen passivated nanopores in graphene and h-BN membranes. In these complex systems the classical potentials cannot properly account for the physics at play. We demonstrate that ion separation works well for the h-BN by imposing a barrier of 0.13 eV and 0.24 eV for Na+ and Cl- permeation respectively, compared to the graphene where the Cl- ion faces a negative barrier of 0.68 eV and is prone toward blockade and Na+ permeation is associated with a slightly negative barrier of 0.03 eV. From the change in the solvation shell, we get the following trend: Na/h-BN > Na/G > Cl/G > Cl/h-BN. We argue that the trend in the permeation barrier changes to Cl-h-BN > Na-h-BN > Na-G > Cl-G due to a combination of several interactions, including the distortion of the water network induced by the ions, the ion-water interaction, and the ion-nanopore interaction. Overall, the desalination performance of h-BN surpasses that of their graphene counterparts.

This study aimed to investigate the impact of incorporating indium tin oxide (ITO) nan particles (NPs) with zinc oxide (ZnO) NPs into flexible dye-sensitized solar cells (FDSSCs). ZnO and ITO NPs were separately prepared using the sol-gel method, followed by hybridization of ZnO NP/ITO NP and characterization using techniques such as TEM, SEM, XRD, UV-Vis spectros-copy, PL spectroscopy and cyclic voltammetry (CV). TEM analysis showed hexagonal struc-tures and small sphere-like nanoparticles with mean diameters of 15.22 ± 11 nm for ZnO NPs and 14.54 ± 16 nm for ZnO NPs/ITO NPs. SEM images revealed uniform dispersion and smooth surface morphology, while XRD confirmed the crystalline nature of both ZnO and hybrid NPs, indicating specific crystallographic planes with consistent sizes. UV-Vis spectroscopy demonstrated a redshift in wavelength upon adding ITO NPs, suggesting an impact on the bandgap of ZnO NPs. PL spectra exhibited a broad visible emission peak at 535 nm. These findings enhance our understanding of the optical behavior and interaction between ITO and ZnO NPs in hybrid nanostructures. The study concluded that the ITO NPs improve FDSSC performance by enhancing charge separation and transport, leading to increased photocurrent production, with the characterization techniques providing valuable insights for future research and applications.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in rodents (mice, rats, rabbits) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023–31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3, and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

Considering the high potential of hydrogen (H₂) as a clean energy carrier, the implementation of high performance and cost-effective biohydrogen (bioH₂) purification techniques is of vital importance, particularly in fuel cell applications. In this context, membrane technology is a potentially energy-saving solution to obtain high-quality biohydrogen. The most promising poly(ionic liquid) (PIL) - ionic liquid (IL) composite membranes previously studied by our group for CO₂/N₂ separation, containing pyrrolidinium-based PILs with fluorinated or cyano-functionalized anions, were chosen as starting point to explore the potential of PIL–IL membranes for CO₂/H₂ separation. The CO₂ and H₂ permeation properties at the typical conditions of biohydrogen production (T =308 K and 100 kPa of feed pressure) were measured and discussed. PIL–IL composites prepared with [C(CN)₃]^– anion showed higher CO₂/H₂ selectivities and H₂ diffusivities compared to those containing [NTf₂]^– anion. All the membranes revealed CO₂/H₂ separation performances above the upper bound for this specific separation, highlighting the composite incorporating 60 wt% of [C₂mim][C(CN)₃] IL.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

In the last decade a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behaviour of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis with a tumor supressor role in some cases, but increased expression in several high grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, early results suggested a protective role of Piezo2, but posterior works resulted in a relationship between Piezo2 expression and the highly-aggressive triple negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow up was chosen to study Piezo2 expression and clarify its clinical implications, using the same immunohistochemical valuation performed for other breast carcinoma parameters. Fisher exact was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have a diminished score for Piezo2. A similar association was found between Piezo2 expression and perineurial invasion.

The next generation network requires not only ultra high data rate, global coverage and connectivity, but also reducing network deployment costs and energy consumption. The emergence of reconfigurable intelligent surface (RIS) technology provides an effective way to improve efficiency and reduce cost, while the passive elements bring new challenges of channel estimation (CE) and beam tracking. For a RIS-aided multiple-input and single-output (MISO) system, in this paper, to achieve the channel state information (CSI), we propose a principle component analysis (PCA) based staged channel estimation method. Based on the estimated channel, we propose a deep learning (DL) based beam tracking scheme to realize low-complexity RIS reflection coefficient design, which effectively improves the signal-to-noise ratio (SNR) at the user side. Simulation results verify our proposed channel estimation scheme based on PCA and beam tracking scheme based on DNN for the semi-active RIS-aided MISO systems can obtain approximate performances with much lower computational complexity.

Giant unilamellar vesicles (GUVs) are membrane model used to study membrane properties. Electroformation is one of the methods used to produce GUVs. During electroformation protocol dry lipid film is formed. Drying of the lipid film induce Cholesterol (Chol) demixing artifact, in which Chol forms anhydrous crystals, where these crystals does not participate in formation of vesicles. This leads to a lower Chol concentration in the vesicle bilayers compared to the Chol concentration in the initial lipid solution. To address this problem, we propose novel electroformation protocol that includes rapid solvent exchange, plasma cleaning and spin-coating methods to produce GUVs. We tested the protocol focusing on vesicles with high Chol content using different spin-coating durations and vesicle types deposition. Additionally, we compared the novel protocol using completely dry lipid film. The optimal spin-coating duration for vesicles made out of phosphatidylcholine/Chol mixture was 30 s. Mulitlamellar vesicles (MLVs), large unilamellar vesicles (LUVs) obtained by extrusion of MLVs through 100 nm membrane pores and LUVs obtained by extrusion of previously obtained LUVs through 50 nm membrane pores were deposited on electrode for 1.5/1 Chol/phosphatidylcholine lipid mixture and the results were compared. Electroformation using all three deposited vesicle types gave a high GUVs yield, but deposition of LUVs obtained by extrusion of MLVs through 100 nm membrane pores gave the most reproducible results. Using deposition of these LUVs, we produced GUVs with high yield for 6 different Chol concentrations (from 0 % to 71.4%). Using protocol that includes dry lipid film GUVs yield was lower and Chol demixing artifact was induced, proving that the lipid film should never undergo drying when Chol content is high.

Artemisia absinthium (A. absinthium) leaf extract was successfully used to create zinc oxide nanoparticles (ZnO NPs), and their properties were investigated via several techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), Fourier transform infrared (FTIR), and UV–Vis spectroscopy. SEM analysis confirmed the spherical and elliptical shapes of the particles. Three different zinc peaks were observed via EDX at energies of 1, 8.7, and 9.8 keV, together with a single oxygen peak at 0.5 keV. XRD analysis identified ZnO NPs as having a hexagonal wurtzite structure with a particle size that decreased from 24.39 to 18.77 nm, and with an increasing surface area (BET) from 4.003 to 6.032 m2/g for the ZnO (without extract) and green ZnO NPs, respectively. FTIR analysis confirmed the groups of molecules that were accountable for stabilizing and minimizing the ZnO NPs, which was apparent at 3400 cm. Using UV–Vis spectroscopy, the band gap energies (Egs) for the green ZnO and ZnO (without extract) NPs were estimated, and the values were 2.65 and 2.79 eV, respectively.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Voltage-gated Ca²⁺ (Ca_v) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Ca_v channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Ca_v channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

The nano size, physical and chemical properties of Au and Ag nanoparticles (NPs) allow them to be used in medicine or plant protection, but chemical solvents used during synthesis makes them toxic and pose a threat to the environment. Chemical NPs synthesis can be replaced by in vivo synthesis in which independently growing plants such as alfalfa take up and then split the precursor in their cells down to nano size using synthesis-promoting solvents–biomolecules, which can break down materials without free radicals and has anti-inflammatory, antioxidant effects, making NPs environmentally benign. In this study, two-week-old seedlings of two Medicago sativa L. genotypes, ‘Kometa’ and ‘la Bella’, were exposed to two precursors (AgNO3, HAuCl4) for 24 and 48 h to determine whether in vivo synthesis is possible. Double-blazed and certain wavelength spectrophotometry and confocal microscopy confirmed, statistically significant (P<0.05) changes in light absorption and light fluorescence compared to the control. Confocal microscopy showed both precursors visible in the roots of both genotypes. Currently, NPs synthesis and visualisation methods require a complex, expensive and time-consuming sequence of methods. It is important to find an effective, environmentally friendly, and as cheap and simple as possible method for the biosynthesis of NPs.

We report the synthesis and characterization of Poly Methyl-Meth-Acrylate (PMMA)/Poly vinylalcohol (PVA) polymeric blend doped with different concentrations of Copper oxide (CuO) nanoparticles (NPs). The (PMMA-PVA)/CuO nanocomposite hybrid thin films (wt. % = 0%, 2%, 4%, 8%, and 16%) of CuO NPs are deposited on glass substrates via dip-coating technique. The transmittance (T%), reflectance (R%), the absorption coefficient (α), the optical constants [refractive index (n), extinction coefficient (k)], optical dielectric functions [ɛ',ɛ''] are investigated and interpreted. Tauc, Urbach, Spitzer-Fan, and Drude models are employed to calculate the optical bandgap energy (Eg) and the optoelectronic parameters of the nanocomposite thin films. The refractive index and optical bandgap energy of of (PMMA-PVA) polymeric thin film are found to be (1.5 to 1.85) and 4.101 eV, respectively. Incorporation of specific concentrations of CuO-NPs in (PMMA-PVA) polymeric thin films leads to a noticeable decrease in the optical bandgap energy and to an increase of the refractive index. Moreover, Fourier Transform Infrared Spectroscopy (FTIR) transmittance spectra are measured and analyzed for undoped and doped polymeric thin films to pinpoint the major vibrational modes in the spectral range (500 and 4000 cm-1), as well as, the nature of network bonding in both systems. Thermal stability of thin films is investigated by performing thermogravimetric analysis (TGA). The TGA thermograms confirm that both doped polymeric thin films are thermally stable at temperatures below 110°C which enables them to be attractive for a wide range of optical and optoelectronic applications. Our results indicate that optical, vibrational and thermal properties of both polymeric thin films can be tuned for specific applications by the appropriate corporation of particular concentrations of CuO-NPs.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Redox mediators comprising I–, Co3+, and Ti3C2Tx MXene were applied to dye-sensitized solar cells (DSCs). In the as-prepared DSCs (I-DSCs), wherein hole conduction occurred via the redox reaction of I−/I3− ions, the power conversion efficiency (PCE) was not altered by the addition of Ti3C2Tx MXene. The I-DSCs were exposed to light to produce Co2+/Co3+-based cells (Co-DSCs), wherein the holes were transferred via the redox reaction of Co2+/Co3+ ions. A PCE of 9.01% was achieved in a Co-DSC with Ti3C2Tx MXene (Ti3C2Tx-Co-DSC), which indicated an improvement from the PCE of a bare Co-DSC without Ti3C2Tx MXene (7.27%). It was also found that the presence of Ti3C2Tx MXene in the redox mediator increased the hole collection, dye regeneration, and electron injection efficiencies of the Ti3C2Tx-Co-DSC, leading to an improvement in both the short-circuit current and the PCE when compared with those of the bare Co-DSC without MXene.

(1)Background：To date, no studies have epidemiologically examined whether the concentration of particulate matter (PM) 2.5 and its ionic components is related to the prevalence of skin symptoms. Therefore, this study aimed to clarify this association in patients with allergic diseases. (2)Methods: From February 1 to May 31, 2020, we evaluated the daily prevalence of skin symptoms in outpatients with allergic diseases being treated at Fukuoka Hospital, Fukuoka, Japan, and measured the concentration of PM2.5 and its ionic components. （3）Results: Univariate analysis showed a statistically significant association between skin symptoms and the concentration of PM2.5 and the ionic components SO42-, NH4+, K+, and Mg2+, and multivariate analysis showed a statistically significant association between the daily prevalence of skin symptoms and the concentration of the ionic components SO42- or Mg2+. (4)Conclusions: Our findings indicate that the concentration of some PM2.5 ionic components may affect skin symptoms in patients with allergic diseases.

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.

Nanoscience is a rapidly growing science stream that has been one of the cost-effective and energy-efficient approaches with wide applications. Water pollution is a major issue that is increasing continuously due to anthropogenic activities and several organic and inorganic contaminants. To overcome this issue, nanoparticles (NPs) have been successfully used to treat water. These NPs possess many beneficial applications in many fields like agriculture, cosmetics, photoconductors, environmental biotechnology, glass and alloy production, solar cells, nanomedicine and drug deliveries, biosensors, food industries, etc. The properties comprising high surface area, greater chemical reactivity, and mechanical properties play a vital role in imparting such beneficiary properties. As a result, there has been an increasing demand for the synthesis of NPs. However, excess usage of NPs further creates toxic by-products. Therefore, scientists and researchers are now focussing on the biogenic synthesis of NPs. The biological routes of NP synthesis have been crucial because they are eco-friendly and environmentally safe. This chapter highlights the usage of different approaches and biogenic sources for the production of NPs. It also discusses the recent advancement in the use of biogenic NPs with respect to applications for wastewater treatment.

Solid polymer electrolytes and composite polymer electrolytes serve as crucial components in all-solid-state energy storage devices. Structural batteries and supercapacitors present a promising alternative for electric vehicles, integrating structural functionality with energy storage capability. However, despite their potential, these applications are hampered by various challenges, particularly in the realm of developing new solid polymer electrolytes that require more investigations. In this study, novel solid polymer electrolytes and composite polymer electrolytes were synthesized using epoxy resin blends, ionic liquid, lithium salt, and alumina nanoparticles, and subsequently characterized. Among the formulations tested, the optimal system, designated as L70P30ILE40Li1MAl2 and containing 40 wt.% of ionic liquid and 5.7 wt.% of lithium salt, exhibited exceptional mechanical properties. It displayed a remarkable storage modulus of 1.2 GPa and reached ionic conductivities of 0.085 mS/cm at 60°C. Furthermore, a proof-of-concept supercapacitor was fabricated, demonstrating the practical application of the developed electrolyte system.

We report a broadband radio frequency (RF) channelizer with up to 92 channels using a coherent microcomb source. A soliton crystal microcomb, generated by a 49 GHz micro-ring resonator (MRR), is used as a multi-wavelength source. Due to its ultra-low comb spacing, up to 92 wavelengths are available in the C band, yielding a broad operation bandwidth. Another high-Q MRR is employed as a passive optical periodic filter to slice the RF spectrum with a high resolution of 121.4 MHz. We experimentally achieve an instantaneous RF operation bandwidth of 8.08 GHz and verify RF channelization up to 17.55 GHz via thermal tuning. Our approach is a significant step towards the monolithically integrated photonic RF receivers with reduced complexity, size, and unprecedented performance, which is important for wide RF applications ranging from broadband analog signal processing to digital-compatible signal detection.

Structural biology has a strong interest in ion channels, a diverse group of membrane proteins. This group has long remained difficult to study, but much progress has been made in recent decades with improvements in biochemical methods and computational procedures. Voltage-gated ion channels undergo conformational changes upon functioning, and multiple models of activation mechanisms were proposed based on experimental data. This review focuses on the structural studies of the functioning of voltage-gated ion channels, which are accompanied by conformational changes in proteins, and the methodological advances that allow their observation. Modern experimental methods that allow obtaining ion channel proteins in specific functional states are discussed, including cryoelectron microscopy and cryoelectron tomography. Finally, new algorithms for studying the conformational mobility of proteins have been developed, which help to better understand the mechanisms of ion channel domain movements.

Routing quantum information among different nodes in a network is a fundamental prerequisite for a quantum internet. While single-qubit routing has been largely addressed, many-qubit routing protocols have not been intensively investigated so far. Building on the many-excitation transfer protocol in Ref. , we apply the perturbative transfer scheme to a two-excitation routing protocol on a network where multiple two-receivers block are coupled to a linear chain. We address both the case of switchable and permanent couplings between the receivers and the chain. We find that the protocol allows for efficient two-excitation routing on a fermionic network, although for a spin-12 network only a limited region of the network is suitable for high-quality routing.

Magnetic nanoparticles are met across many biological species ranging from magnetosensitive bacteria, fishes, bees, bats, rats, birds, to humans. They can be both of biogenetic origin and due to environmental contamination, being either in paramagnetic or ferromagnetic state. The energy of such naturally occurring single-domain magnetic nanoparticles can reach up to 10-20 room k_BT in the magnetic field of the Earth, which naturally led to supposition that they can serve as sensory elements in various animals. This work explores within a stochastic modeling framework a fascinating hypothesis of magnetosensitive ion channels with magnetic nanoparticles serving as sensory elements, especially, how realistic it is given a highly dissipative viscoelastic interior of living cells and typical sizes of nanoparticles possibly involved.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of random variables has with respect to a target variable into three types of components: redundant, synergistic, and unique. Classical information theory alone does not provide a unique way to decompose information in this manner and additional assumptions have to be made. Inspired by Kolchinsky's recent proposal for measures of intersection information, we introduce three new measures based on well-known partial orders between communication channels and study some of their properties.

Background. Telegram, an Industry 4.0 style Russian-born communication service, is one of the world’s most widespread communication platforms despite Putin’s censorship. The availability of channels and bots has opened as a broadcast channel for any media outlet. Objetives. We asked the following questions: Do Spanish media outlets use Telegram channels? Which media outlets? Are they verified? What is their volume of subscribers? Can this information be used to rank media outlets? We identified many media channels and numerous variables were collected from each one. Results and conclusions. Forty-two Spanish media outlets have Telegram channels, 26 of which are ranked in the directory. Less than half of these channels are verified by the platform, and only three are linked to their website. This lack of verification could lead to the proliferation of fake channels. We created a ranking, and the top-10 includes two foreign, six national, and two regional media outlets.

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP, TRPC may form homo or heterotetrameric ion channel, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase of the expression of different TRPC isoforms has been observed in different animal model of heart infarcts, and in vitro experimental model of ischemia and reperfusion. TRPC-mediated increase of the intracellular Ca²⁺ concentration seems required for the activation of signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we will highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion, and to heart infarction.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).

G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30 % of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specific effects of cholesterol mediated via its direct high-affinity binding to the receptor and non-specific effects mediated by cholesterol-induced changes in the properties of the membrane. Cholesterol binds to many GPCRs at both canonical and non-canonical binding sites. It allosterically affects ligand binding to and activation of GPCRs. Also, it changes the oligomerization state of GPCRs. In this review, we consider a perspective of the potential for the development of new therapies that are targeted at manipulating the level of membrane cholesterol or modulating cholesterol binding sites on to GPCRs.

With the developments of smart technologies, the use of rare earth elements (REEs) knows a widespread use, thus, their importance as valuable and strategic metals boosted to levels never known before. Due to their scarcity in Earth crust, the recovery of these elements from secondary resources also knows further developments. Traditional pyrometallurgical and hydrometallurgical processing, though of wide use, in the recovery of these REEs, have some environmental drawbacks, thus, the development of new recovery approaches are under developments. Here, Solvometallurgy appeared as a friendly environmental technology, and ionic liquids and deep eutectic solvents re-sulted as a first-row chemicals to be used in the different unit operations used in solvometallurgical processing: leaching, liquid-liquid extraction, ion exchange (adsorption), precipitation and elec-trolysis. This manuscript reviewed the most recent literature concerning the use of ionic liquids and deep eutectic solvents in the recovery of REEs from various sources.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

(1) Background: In nervous system information is conveyed by a sequence of action potentials, called spikes-trains. As MacKay and McCulloch proposed, spike-trains can be represented as bits sequences coming from Information Sources. Previously, we studied relations between Information Transmission Rates (ITR) carried out by the spikes, their correlations, and frequencies. Here, we concentrate on the problem of how spikes fluctuations affect ITR. (2) Methods: The Information Theory Method developed by Shannon is applied. Information Sources are modeled as stationary stochastic processes. We assume such sources as two states Markov processes. As a spike-trains' fluctuation measure, we consider the Standard Deviation sigma, which, in fact, measures average fluctuation of spikes around the average spike frequency. (3) Results: We found that character of ITR and signal fluctuations relation strongly depends on the parameter s which is a sum of transitions probabilities from no spike state to spike state and vice versa. It turned out that for smaller s (s<1) the quotient ITR\sigma has a maximum and can tend to zero depending on transition probabilities. While for s large enough (1<s) the ITR\sigma is separated from 0 for each s. Similar behavior was observed also when we replaced Shannon entropy terms in Markov entropy formula by their approximation with polynomials. We also show that the ITR quotient by Variance behaves in a completely different way. (4) Conclusions: Our results show that for large transition parameter s the Information Transmission Rate by sigma will never decrease to zero. Specifically, for 1<s<1.7 the ITR will be always, independently on transition probabilities which form this s, above the level of fluctuations, i.e. in this case we have sigma<ITR. Thus, we conclude that in a more noisy environment, to get appropriate reliability and efficiency of transmission, Information Sources with higher tendency of transition from the state no spike to spike state and vice versa should be applied.

Physical reason for the small scale tortuosity observed in sparks and lightning channels is unknown at present. In this paper it is suggested that the small scale tortuosity of the discharge channels is caused by the natural tendency for subsequent leader streamer bursts to avoid each other but at the same time to align as much as possible along the direction of the background electric field. This process will give rise to a discharge channel that re-orients in space during each streamer burst creating the small scale tortuosity.

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut-brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; while A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Also, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

Shut-in after fracturing is generally adopted for wells in shale oil reservoirs, and imbibition occurring in matrix nanopores has been proven as an effective way to improve recovery. In this research, the molecular dynamics (MD) simulation was used to investigate the effects of wettability and pressure on nanopores imbibition during shut-in for a typical shale reservoir Jimsar. The results indicate that the microscopic advancement mechanism of the imbibition front is the competitive adsorption between “interfacial water molecules” at the imbibition front and “adsorbed oil molecules” on the pore wall. The essence of spontaneous imbibition involves the adsorption and aggregation of water molecules onto the hydroxyl groups on the pore wall. The flow characteristics of shale oil suggest that the overall push of the injected water to the oil phase is the main reason for the displacement of adsorbed oil molecules. Thus, shale oil especially the heavy hydrocarbon component in the adsorbed layer tends to slip on the walls. However, the weak slip ability of heavy components on the wall surface is an important reason that restricts the displacement efficiency of shale oil during spontaneous imbibition. The effectiveness of spontaneous imbibition is strongly dependent on the hydrophilicity of the matrix pore's wall. The better hydrophilicity of the matrix pore's wall facilitates higher levels of adsorption and accumulation of water molecules on the pore wall and requires less time for “interfacial water molecules” to compete with adsorbed oil molecules. During the forced imbibition process, the pressure difference acts on both the bulk oil and the boundary adsorption oil, but mainly on the bulk oil, which leads to the occurrence of wetting hysteresis. Meanwhile, shale oil still existing in the pore always maintains a good stratified adsorption structure. Because of the wetting hysteresis phenomenon, as the pressure difference increases, the imbibition effect gradually increases, but the actual capillary pressure gradually decreases and there is a loss in the imbibition velocity relative to the theoretical value. Simultaneously, the decline in hydrophilicity further weakens the synergistic effect of pressure difference because of the more pronounced wetting hysteresis. Thus, selecting an appropriate well pressure enables cost savings and maximizes the utilization of the formation's natural power for EOR.

In this study, a novel absorbable hemostatic agent was developed using carrageenan (CRG) as a natural polymer and cerium oxide nanoparticles (CeO2 NPs).  CRG-CeO2-0.5 and CRG-CeO2-1 composites were prepared by compositing CRG and CeO2 at a weight ratio of 200:1 and 100:1, respectively. Physio-chemical and structural properties of these compounds were studied and compared with pristine CRG. Upon incorporation of CeO2 nanoparticles into the CRG matrix, significant reductions in hydrogel degradation were observed. In addition, it was noted that CRG-CeO2 exhibited better antibacterial and hemostatic properties than CRG hydrogel without CeO2.The biocompatibility of the materials was tested using the NIH 3T3 cell line and all samples were found to be nontoxic. Particularly, CRG-CeO2-1 demonstrated superior hemostatic effects, biocompatibility, and a lower degradation rate since more CeO2 Nps were present in the CRG matrix. Therefore, CRG-CeO2-1 has the potential to be used as a hemostatic agent and wound dressing.

As novel materials for carbon capture, phase change solvents can separate into two immiscible phases during the CO2 capturing procedure under a certain temperature. The solvent systems can significantly decrease the energy consumption since the solvents can be regenerated by only heating the rich-CO2 phase. In this work, amino acid ionic liquids (AAILs) were synthesized using quaternary ammonium salts and amino acids as raw materials, and the aqueous solutions were prepared as novel liquid-solid phase change solvents. The results showed that the solvents had excellent CO2 absorption capacity, and the AAILs functionalized by glycine and tryptophan exhibited significant phase change properties. The mechanism of phase-change of the solvent were mainly due to the lower solubility of the product after reaction between AAILs and CO2. The solvent with tryptophan as anion could be regenerated by only heating the CO2-riched solid phase, which might significantly decrease energy consumption of regeneration. And the absorbent could be reused with the regenerated absorption ratio up to 79%. The solvent system has great potential in industrial application due to the easy operation process and efficient recycling ability.

The present study provides molecular insight into the mechanisms underlying energy dissipation and lubrication of a smooth contact lubricated by an ionic liquid. We have performed normal and lateral force measurements with a surface forces apparatus and by colloidal probe atomic force microscopy on following model systems: 1-ethyl-3-methyl imidazolium bis-(trifluoro-methylsulfonyl)imide, in dry state and in equilibrium with ambient (humid) air; the surface was either bare mica or functionalized with a polymer brush. The velocity-dependence of the friction force reveals two different regimes of lubrication, boundary-film lubrication, with distinct characteristics for each model system, and fluid-film lubrication above a transition velocity V*. The underlying mechanisms of energy dissipation are evaluated with molecular models for stress-activated slip and flow, respectively. The stress-activated slip assumes that two boundary layers (composed of ions/water strongly adsorbed to the surface) slide pass each; the bond dynamics and the strength of the interaction at the slip plane dictate the change in friction -decreasing, increasing or remaining constant- with velocity in the boundary-film lubrication regime. Above a transition velocity V*, friction monotonically increases with velocity in the three model systems. Here, layers of ions slide past each (“flow”) under a shear stress and friction depends on a shear-activation volume that is significantly affected by confinement. The proposed friction model provides a molecular perspective of the lubrication of smooth contacts by ionic liquids and allows identifying the physical parameters that control friction.

Nanocellulose has gained increasing attention during the past decade, which is related to its unique properties and wide application. In this paper, nanocellulose was produced by hydrolysis with ionic liquids (1-ethyl-3-methylimidazole acetate (EmimOAc) and 1-allyl-3-methylimidazolium chloride (AmimCl)) from microcrystalline cellulose (Avicel and Whatman) subjected to enzymatic pretreatment. The obtained material was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscope (SEM) and thermogravimetric analysis (TG). The results showed that the nanocellulose had a regular and spherical structure with a diameter of 30-40 nm and exhibited lower crystallinity and thermal stability than the material after hydrolysis with Trichoderma reesei enzymes. However, the enzyme-pretreated Avicel had a particle size of about 200 nm and a cellulose II structure. A two-step process involving enzyme-pretreatment and hydrolysis with ionic liquids resulted in the production of nanocellulose. Moreover, the particle size of nanocellulose and its structure depend on the ionic liquid used.

Airborne micro- and nanoplastics are widely spread and pose a risk to human health. The effects of virgin (v) and home oxidised (ox) nano- and micropolystyrene (nPS/mPS) (0.1 and 1 µm) were studied on the human alveolar cells (A549). Ox-nPS/mPS, simulating photoaging, allowed effects due to environmental wear to be assessed. Cellular uptake was quantified using FITC-functionalised nPS/mPS, while cytotoxicity, changes in the acidic compartment, ROS production, mitochondrial function and DNA damage were assessed to study the effects of internalised v- and ox-nPS/mPS. The uptake was dose-dependent and very fast, since, at the lowest dose, 20.8% and 21.8% of nPS and mPS, respectively, were internalised after 1 h. Compared to v-, significant ROS increases, DNA damage and mitochondrial impairment were observed after exposure to ox-nPS/mPS. The enhancement of effects due to environmental aging processes highlighted the true potential impact on human health of these airborne pollutants.

Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptors in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptors innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting these nociceptors is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptors in migraine, the challenges of current antimigraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

Two histamine receptor subtypes (HR), namely H1R and H4R, as key components, are involved in the transmission of histamine-induced itch. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. Aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo and in vitro via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons. The TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch and reduced Ca2+ influx into the neurons. The TRPA1 inhibitor reduced H4R-induced itch and both H1R- and H4R-induced Ca2+ influx. In conclusion, these results indicate that both channels, TRPV1 and TRPA1 are involved in the transmission of histamine-induced pruritus.

This study aimed to investigate the ability of lactic acid bacteria to remove cholesterol in simulated gastric and intestinal fluids. The findings showed that the amount of cholesterol removed was dependent on the biomass, viability, and bacterial strain. Additionally, some cholesterol binding was stable and not released during gastrointestinal transit. The presence of cholesterol affected the fatty acid profile of bacterial cells, which could potentially influence their metabolism and functioning. However, adding cholesterol did not significantly impact the survival of lactic acid bacteria during gastrointestinal transit. Moreover, the study did not find significant effects of storage time, passage, or bacterial culture type on the cholesterol content of fermented dairy products. The researchers observed differences in cell survival among lactic acid bacteria strains in simulated gastric and intestinal fluids, depending on the environment. Furthermore, dry matter content, such as high milk protein, was more protective of bacterial cells during gastrointestinal transit than fat content. Future research should aim to better understand the impact of cholesterol on lactic acid bacteria metabolism and identify potential health benefits or risks.

In this study, we aim to evaluate how cyclodextrin molecules affect the hydrophilicity and selec-tivity of PVDF membrane. Herein, we prepared PVDF-PVP(1-x) β-CDx membranes, with x rang-ing from 0 to 1 wt%. The membranes were deeply characterized by means of X-ray diffraction (XRD), attenuated total reflectance infrared (ATR-IR), Raman spectroscopies, Thermal gravimet-ric analysis (TGA), Contact angle measurement (CA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The study unequivocally demonstrates the effectiveness of the addition of β-CD molecules on membranes' structural, morphological, and dielectric properties. Adding 0.25wt% β-CD enhanced hydrophilicity, with CA decreasing from 72.6° to 56° and roughness decreasing from 81 to 29 nm. The PVDF-PVP(1-x) β-CDx membranes were then fully characterized using electrochemical impedance spectroscopy (EIS) to determine their dielectric properties, which clearly showed that the presence of β-CD induced polarization of the mem-brane. The separation of various dyes with different sizes and charges was utilized. These dyes included methylene blue (MB, positive, 0.504 nm), methyl red (MR, neutral, 0.487 nm), rose Bengal (RB, negative, 0.588 nm), and brilliant blue (BB, negative, 0.798 nm). Based on our re-search, we found that the membrane's selectivity is determined by both exclusion factors (such as size and dielectric properties) and inclusion inside the β-CD cage. We found that using alpha-CD instead of beta-CD led to the disappearance of dye inclusion. These findings strongly sug-gest that β-CD molecules can be a viable solution for dye removal from wastewater.

The preservative qualities of individual ionic compounds on the infectivity of T4 virions were elucidated. T4 virions were immersed in quasi-pure ionic solutions prior to the adsorption process, and the pfu values of these were measured following the conventional method. In neutral ionic solutions, the minimum and the optimum concentrations for preservative qualities were corresponded with the results obtained from the multi-ionic media/buffers. In acid and alkali solutions, phages show tolerances at a pH range of 5-11 in multi-ionic media/buffers. T4 virions show no tolerance in quasi-pure acid, neutral and weak alkaline conditions. The preservative quality of T4 virions was jumped up in over 10-1 mM OH- solution, equivalent to pH value over 10, which is corresponding to the pKa of the deprotonation of the DNA bases G and T. Infectivity was lost below 10-1 mM OH- and higher than 10 mM OH-. These results implicate the maintaining of infectivity of a virion may need the flexibility of the intra-capsid DNA by deprotonation.

K+ channels do play a role in cell shape changes observed during cell proliferation and apoptosis. Research suggested that the dynamics of aggregation of Aquaporin-4 (AQP4) into AQP4-OAPs isoforms can trigger cell shape changes in malignant glioma cells. Here, we investigated the relationship between AQP4 and some K+ channels in the malignant glioma U87 line. The U87 cells transfected with the human M1-AQP4 and M23-AQP4 isoforms were investigated for morphology, gene expression of KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, and Cyclin genes by RT-PCR, recording the whole-cell K+ ions currents by patch-clamp experiments. AQP4 aggregation into OAPs increases the plasma membrane functional expression of the Kir6.2 and SUR2 subunits of the KATP channels, and of the KCNMA1 of the BK channels in U87 cells leading to a large increase in inward and outward K+ ion currents. These changes were associated with changes in morphology with a decrease in cell volume in the U87 cells and an increase in the ER density. These U87 cells accumulate in the mitotic and G2 cell cycle. The KATP channel blocker zoledronic acid reduced cell proliferation in either M23 AQP4-OAPs and M1 AQP4-tetramers transfected cells leading to early and late apoptosis, respectively. BK channel sustains the efflux of K+ ions associated with the M23 AQP4-OAPs expression in the U87 cells, but it is downregulated in the M1 AQP4-tetramers cells; KATP channels are effective in the M1 AQP4-tetramers and M23 AQP4-OAPs cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramers cell phenotype inhibiting KATP channels and inducing early apoptosis.

We study two fundamental linguistic channels ‒ the Sentences and the Interpunctions channels ‒ and show they can reveal deeper connections between texts. The theory applied does not follow the actual paradigm of linguistic studies. As study‒case, we consider the Greek New Testament, with the purpose of determining mathematical connections between its texts and possible differences in writing style (mathematically defined) of writers, and in reading skill required to their readers. The analysis is based on deep‒language parameters and communication/information theory. To set the New Testament texts in the larger Greek Classical Literature, we consider texts written by Aesop, Polybius, Flavius Josephus and Plutarch. The results largely confirm what scholars have found about the New Testament texts giving, therefore, credibility to the theory. The gospel according to John is very similar to Fables written by Aesop. Surprisingly, the Epistle to the Hebrews and Apocalypse, are each other “photocopy” in the two linguistic channels, and not linked to all other texts. These two texts deserve further study by historians of the early Christian Church Literature at the level of meaning, readers and possible Old Testament texts which might have influenced them. The theory can guide scholars to study any literary corpus.

Quantum Correlations are studied extensively in quantum information domain. Entanglement Measures and Quantum Discord are good examples of these actively studied correlations. Detection of violation in Bell inequalities is also a widely active area in quantum information theory world. In this work, we revisit the problem of analyzing the behavior of quantum correlations and violation of Bell inequalities in noisy channels. We extend the problem defined in a recent study by observing the changes in negativity measure, quantum discord and a modified version of Horodecki measure for violation of Bell inequalities under amplitude damping, phase damping and depolarizing channels. We report different interesting results for each of these correlations and measures. All these correlations and measures decrease under decoherence channels, but some changes are very dramatical comparing to others. We investigate also separability conditions of example studied states.

All-solid-state lithium batteries (ASSLBs) using argyrodite electrolyte materials have shown promise for applications in electric vehicles (EVs). However, understanding the effects of pro-cessing parameters on the ionic conductivity of these electrolytes is crucial for optimizing battery performance and manufacturing methods. This study investigates the influence of electrolyte op-erating temperature, electrolyte operating pressure, electrolyte pelletization pressure, and electro-lyte pelletizing temperature on the ionic conductivity of Li6PS5Cl0.5Br0.5 argyrodite electrolyte (AmpceraTM, D50=10 µm). A specially designed test cell is employed for the experimental meas-urements, allowing for controlled pelletization and testing within the same tooling. The results demonstrate the significant impact of the four parameters on the ionic conductivity of the argy-rodite electrolyte. The electrolyte operating temperature has a more pronounced effect than oper-ating pressure, and pelletizing temperature exerts a greater influence than pelletizing pressure. This study provides graphs that aid in understanding the interplay between these parameters and achieving desired conductivity values. It also establishes a baseline for the maximum pelletizing temperature before undesirable degradation of electrolyte occurs. By manipulating the pelletizing pressure, operating pressure, and pelletizing temperature, battery engineers can achieve the desired conductivity for specific applications. The findings emphasize the need to consider operating conditions to ensure satisfactory low-temperature performance, particularly for EVs. Overall, this study provides valuable insights into processing and operating conditions for ASSLBs utilizing Li6PS5Cl0.5Br0.5 argyrodite electrolyte.

Preclinical evidence suggests that voltage gradients can act as a kind of top-down master regulator during embryogenesis and orchestrate downstream molecular-genetic pathways during organ regeneration or repair. Moreover, electrical stimulation shifts response to injury towards regeneration instead of healing or scarring. Cancer and embryogenesis not only share common phenotypical features, but also commonly upregulated molecular pathways. Ion channel activity is directly or indirectly linked to the pathogenesis of cancer hallmarks, while experimental and clinical studies suggest that their modulation may exert antitumor effects. A large recent clinical trial served as a proof-of-principle for the benefit of preoperative use of topical sodium channel blockade as a potential anticancer strategy against early human breast cancers. Apart from the obvious importance in perioperative medicine, it calls for the planning of further carefully designed clinical trials to expand on the concept of ion channels as tumor drivers.

Large intelligent surfaces (LIS) promises not only to improve the signal to noise ratio, and spectral efficiency but also to reduce the energy consumption during the transmission. We consider a base station equipped with an antenna array using the maximum ratio transmission (MRT), and a large reflector array sending signals to a single user. Each subchannel is affected by the Rayleigh flat fading, and the reflecting elements perform non-perfect phase correction which introduces a Von Mises distributed phase error. Based on the central limit theorem (CLT), we conclude that the overall channel has an equivalent Gamma fading whose parameters are derived from the moments of the channel fading between the antenna array and LIS, and also from the LIS to the single user. Assuming that the equivalent channel can be modeled as a Gamma distribution, we propose very accurate closed-form expressions for the bit error probability and a very tight upper bound. For the case where the LIS is not able to perform perfect phase cancellation, that is, under phase errors, it is possible to analyze the system performance considering the analytical approximations and the simulated results obtained using the well known Monte Carlo method. The analytical expressions for the parameters of the Gamma distribution are very difficult to be obtained due to the complexity of the nonlinear transformations of random variables with non-zero mean and correlated terms. Even with perfect phase cancellation, all the fading coefficients are complex due to the link between the user and the base station that is not neglected in this paper.

Among the most important variables in the design of falling film microreactors (FFMRs) is the liquid film thickness as well as the gas/liquid interfacial area, which dictate the mass and heat transfer rates. In a previous work conducted in our lab the characteristics of a free-falling Newtonian liquid film have been studied and appropriate correlations have been proposed. In this work the geometrical characteristics of a non-Newtonian shear thinning liquid, flowing in an inclined open microchannel, have been experimentally investigated and design correlations that can predict with reasonable accuracy the features of a FFMR have been proposed. The test section used was an open μ-channel with square cross section (Wo=1200 μm) made of brass which can be set to various inclination angles. The liquid film characteristics were measured by a non-intrusive technique that is based on the features of a μ-PIV system. Relevant CFD simulations revealed that the volume average dynamic viscosity over the flow domain is practically the same as the corresponding asymptotic viscosity value, which can thus be used in proposed the design equations. Finally, a generalized algorithm for the design of FFMRs, containing non-Newtonian shear thinning liquids, is suggested.

Atherosclerotic cardiovascular disease, a leading cause of morbidity and mortality worldwide, is a chronic inflammatory disease, linked to a state oxidative stress, with several well-identified culprits, of which low-density-lipoprotein cholesterol (LDL-C) and lipoprotein(a). No specific treatment is currently available to lower lipoprotein(a). It is, therefore, of paramount importance to identify nutritional factors that could lower lipoprotein(a). Growing evidence shows that although reducing saturated fatty acid (SFA) intake decreases LDL-C, it could increase lipoprotein(a). Optimal dietary recommendations may therefore differ depending on an in-dividual’s baseline lipoprotein(a) and LDL-C levels. Assessing the diet-induced true LDL-C response and net balance of these two atherogenic entities is difficult because LDL-C measurement is confounded by lipoprotein(a) cholesterol content. We have estimated, for the first time, the net atherogenic result of diet-induced variations of both LDL-C and lipoprotein(a), thanks to our new concept of LDLapoB risk equivalent=apoB+lp(a)x5 (in nmol/L). This is illustrated, via the rare case of a physician with very high lipoprotein(a) and hypobetalipoproteinemia. She experiences twice a considerable lipoprotein(a) increase (+32%, + 28mg/dL, + 67nmol/L) and higher LDLapoB risk equivalent (138mg/dL versus 123mg/dL) on a mediterranean diet, low in SFA. A reasonable SFA intake, despite causing marginal LDL-C increase, may be advisable in patients with high lipoprotein(a) who need personalized dietary recommendations.

The accumulation of foam cells in arterial intima and the accompanied chronic inflammation are considered major causes of neoatherosclerosis and restenosis. However, both the underlying mechanism and effective treatment for the disease are yet to be uncovered. In this study, we combined transcriptome profiling of restenosis artery tissue and bioinformatic analysis to reveal that NLRP3 inflammasome is markedly upregulated in restenosis and that several restenosis re-lated DEGs are also targets of mulberry extract, a natural dietary supplement used in traditional Chinese medicine to improve liver vitality. Further pathway enrichment analysis identified MAPK signaling pathway to be involved in the inflammatory response of foam cells. Consistently, immunofluorescence microscopy shows co-localization of NLRP3 with CD68+ macrophages. We then evaluated the efficacy of mulberry extract in inhibiting both the formation of foam cells and their inflammatory response. We demonstrated that mulberry extract suppresses the formation of ox-LDL induced foam cells, possibly by upregulating the cholesterol efflux genes ABCA1 and ABCG1 to inhibit intracellular lipid accumulation. In addition, mulberry extract dampens NLRP3 inflammasome activation by stressing the MAPK signaling pathway. Collectively, our mecha-nistic and functional studies unveil the therapeutic value of mulberry extract in neoatherosclerosis and restenosis treatment by regulating lipid metabolism and inflammatory response of foam cells.

The processes of the sublimation and thermal decomposition of the 1‐ethyl‐3‐methylimidazolium hexafluorophosphate ionic liquid (EMImPF6) were studied by a complex approach including Knudsen effusion mass spectrometry, IR and NMR spectroscopy, and quantum chemical calculations. It was established that the vapor over liquid phase primarily consists of decomposition products under equilibrium conditions. Otherwise, the neutral ion pairs are the only vapor components under Langmuir conditions. To identify the nature of the decomposition products an experiment on the distillation of the ionic liquid was performed and the collected distillate was analyzed. It was revealed by the IR and NMR spectroscopy that EMImPF6 decomposes to substituted imidazole‐2‐ylidene (C6N2H10PF5) and HF. The measured vapor pressure of C6N2H10PF5 reveals a very low activity of the decomposition products (&lt;10–4) in the liquid phase. The absence of significant accumulation of decomposition products in the condensed phase makes it possible to determine the enthalpy of sublimation of the ionic liquid assuming its unchanged activity. The thermodynamics of the EMImPF6 sublimation was studied by Knudsen effusion mass spectrometry. The formation enthalpy of EMImPF6 in ideal gas state was found from combination of the sublimation enthalpy and formation enthalpy of ionic liquid in the condensed state. The obtained value is in good agreement with those calculated by quantum chemical methods.

The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy to topically treat some ocular disorders, as they may protect the entrapped molecules, facilitating drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, modifying the transcorneal penetration of loaded therapeutics. Ex-vivo transcorneal permeation experiments showed that the permeation of hydrophilic drugs (i.e. tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side the permeation of hydrophobic drugs (i.e. dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.

(200 words) Imidazolium ionic liquids containing acetylacetone, thenoyltrifluoroacetone, or 8-hydroxyquinoline, respectively, were used as the extracting agents for the separation of traces of iron (III) from its aqueous solutions with or without citric and oxalic acids. The results show that 8-hydroxyquinoline in imidazolium ionic liquids extract iron quantitatively from all the tested solutions including complexing ones, regardless indications of unexpected iron behavior/speciation.

Microvascular self-healing composite materials have significant potential for application and their mechanical properties need in-depth investigation. In this paper, tensile and compressive properties of woven fabric carbon fiber reinforced polymers (CFRP) laminates containing three-dimensional microvascular channels were investigated experimentally. Several detailed finite element (FE) models were established to simulate the mechanical behavior of the laminate and the effectiveness of different models were examined. The damage propagation process of the microvascular laminates and the influence of microvascular parameters were studied by the validated models. The results show that microvascular channels arranged along the thickness direction (z-direction) of the laminates are critical locations under the loads. The channels have minimal effect on the stiffness of the laminates but causing a certain reduction in strength, which varies approximately linearly with the z-direction channel diameter within its common design range of 0.1~1mm. It is necessary to consider the resin-rich region formed around microvascular channels in the warp and weft fiber yarns of the woven fabric composite when establishing the FE model. And the layers in model should be assigned with equivalent unidirectional ply material in order to calculate the mechanical properties of laminates correctly.

The channels from the superfamily of transient receptor potential (TRP) activated by reactive oxygen species (ROS) are defined as redox channels. Those with the best exposure of the cysteine residues and hence the most sensitive to oxidative stress are TRPC4, TRPC5, TRPV1, TRPV4, and TRPA1, while others, such as TRPM2 and TRPM7 are indirectly activated by ROS. Activation by ROS has different effects on the tumorigenic process: some TRP channels may, upon activation, stimulate proliferation, apoptosis, or migration of cancer cells, while others inhibit these processes, depending on the cancer type, tumoral microenvironment and finally on the methods used for evaluation. Therefore, the use of these polymodal proteins as therapeutic targets is still an unmet need, despite their draggability and modulation by simple and mostly unharmful compounds. In this review, we intend to create some cellular models of the interaction between oxidative stress, TRP channels, and inflammation. Although the crosstalk between the three actors is rather theoretical, we intended to gather the recently published data and proposed pathways of cancer inhibition using modulators of TRP proteins, hoping that the experimental data corroborated with clinical information may finally bring the results from the bench to the bedside.

Objective: In this study, we investigated vitamin D, inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), MHR and plasma atherogenic index (PAI) and possible relationships with insulin resistance in children. Methods: A total of 210 individuals, including 96 children with insulin resistance and 114 children without insulin resistance, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. Result: NLR, PLR, SII and MHR were significantly higher in patients with insulin resistance compared to those without. Fasting insulin, PAI, HOMA-IR, HOMA- were significantly higher and QUICKI was significantly lower in patients with insulin resistance compared to those without insulin resistance. NLR, SII and MHR were lower in normal vitamin D groups than the others were (p

The microfluidic industry recognizes the lack of sensitive and standardized testing methods as one of the major hurdles to overcome before fulfilling its revolutionary promises. Highly ranked upon the list of things in need of testing methods are the internal dimensions of microfluidic structures after chip assembly. This work, performed under the MFMET project, aims to address this challenge by presenting and comparing multiple protocols for measuring the dimensions of internal microfluidic channels of fully assembled transparent chips. The protocols include optical profilometry, optical microscopy and tiled digital imagery. Several standardized chip designs out of two different materials commonly used in microfluidics (D263©bio and TOPAS© COC) were measured by the different protocols. A consistency analysis through normalized error statistics revealed optical profilometry as the preferred method due to its low uncertainty compared to the other protocols and its higher consistency with nominal geometry values. All protocols showed difficulty with vertical depth measurements of internal structures. Associated possible directions of future research are considered including further study of the influence of multiple refractive surfaces on optical profilometry measurements and further investigation of confocal microscopy as a potential measurement method showing promising preliminary results. The influence of the different materials appears to be minimal on optical profilometry, but other materials and method would merit looking into before such an observation might be generalized. In conclusion, the results of this work directly address the current lack of measurement methods for internal microfluidic structures by providing a comprehensive comparison of different protocols, ultimately suggesting a preferred option for immediate application within the microfluidic industry. Additionally, this work offers valuable directions for future research, serving as an initial step in overcoming a significant challenge that impedes the microfluidic industry from realizing its revolutionary potential.

Ionic channels are present in eucaryotic plasmatic and intracellular membranes. They coordinate and control several functions. One of the most diverse ionic channels family are the potassium (K) channels. Within this family are the ATP-dependent potassium channels (KATP), which belong to the potassium rectifier channel family. These channels were initially described in heart muscle, yet they are also present in different types of tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle. In ß-pancreatic cells, KATP are primarily responsible for maintaining membrane potential and for the depolarization mediated insulin release. KATP density/activity seems to be determinant in physiological the outcome, in pancreatic cells decrease of this density/activity may be related to Insulin resistance (IR). In extra pancreatic tissues KATP relation with IR is beginning to be explored. It is possible that in skeletal muscle, the KATP are involved in insulin dependent glucose recapture and that KATP activation leads to IR. In adipose tissue, KATP containing Kir6.2, could be related to increase in free fatty acids and insulin resistance, therefore, pathological processes leading to a prolonged adipocyte KATP inhibition might promote obesity related to insulin resistance. In central nervous system KATP activation can regulate peripheric glycemia and lead to brain IR which could be a much earlier manifestation of peripheral alterations that lead to the development of pathologies such as obesity and type 2 diabetes mellitus. In this review we aim to discuss the KATP channel characteristics, its relationship to known clinical disorders and the mechanisms and potential relations with peripheral and central insulin resistance.

Styryl dyes are generally poor fluorescent molecules inherited from their flexible molecular structures. However, their emissive properties can be boosted by restricting their molecular motions. A tight confinement into inorganic molecular sieves is a good strategy to yield highly fluorescent hybrid systems. In this work, two Mg-aluminophosphate zeotypes (AEL framework, a one-dimensional channeled structure with elliptical pores of 6.5 Å x 4.0 Å; and CHA framework, composed by large cavities of 6.7 Å x 10.0 Å connected by 8-ring narrower windows) were selected for the encapsulation of 4-DASPI dye (trans-4-[4-(Dimethylamino)styryl]-1-methylpyridinium iodide). The synthesis and photophysical properties of 4-DASPI styryl dye occluded within these two types of confinements, AEL and CHA, are optimized and analyzed. The resultant hybrid systems display significantly improved photophysical features compared to 4-DASPI in solution. Molecular simulations reveal a tighter confinement of 4-DASPI in the elliptical channels of AEL, whilst a particular orientation is found within the CHA framework, where one 4-DASPI molecule spans along two adjacent cavities. In the latter scenario, each aromatic ring is positioned on these adjacent cavities and the polymethine chain resides within the 8-ring window, being this confinement slightly less tight than for AEL.

The investigation of plasma channels induced by focused ultra-short 1030-nm laser pulses in bulk of synthetic HPHT diamond revealed strong dependence of their size and shape on the used numerical aperture of the lens (NA=0.15-0.45). It was shown that at loose focusing conditions, it is possible to significantly increase the length of the plasma channel with a slight increase in pulse power, while tight focusing allows to obtain more compact structures in the same range of used powers. Such dependence paves the way to new possibilities in 3D processing of transparent dielectrics, allowing, for example, to vary the spatial parameters of modified regions without changing the setup, but only by controlling the lens aperture, which seems very promising for industrial applications.

The importance of rare earth elements as the basis in the development of new technologies or the improvement of the used ones, made of a necessity its recovery, besides that from raw materials, from waste materials. In this recovery, Hydrometallurgy and its derivative Solvometallurgy, play a key role due to its operational characteristics, which are emphasized with the use of ionic liquids. The manuscript reviewed the most recent advances (2023 and 2024 years) about the use of ionic liquids in the unit operations (leaching and separation technologies) aimed to the recovery of these valuable and strategic metals. Moreover, a comprehensive review about the use of these chemicals in the development of advanced materials containing some of these rare earth elements is presented.

The recovery of precious metals is a project with both economic and environmental significance. In this paper, it presents how to use bacterial mineralization to selectively recover gold from multi-ionic aqueous systems. The Bacillus licheniformis FZUL-63, separated from a landscape lake in FuZhou University, was shown to selectively mineralize and precipitate gold from coexisting ions in aqueous solution. The removal of Au(III) was almost happened in first hour, and FTIR data show that the amino, carboxyl and phosphate groups on the surface of the bacteria are related to the adsorption of gold ions. XPS results implied that Au(III) ions are reduced to monovalent, and then the Au(I) was adsorbed on the bacterial surface at the beginning stage(first hour). XRD results showed the gold biomineralization began about 10 hours after the interaction between Au(III) ions and bacteria. The Au(III) mineralization has been rarely influenced by other co-existing metal ions. TEM analysis shows the gold nanoparticles are polyhedral structure with a particle size of ~20 nm. The Bacillus licheniformis FZUL-63 could selectively mineralize and recover 478 mg/g(dry biomass) gold from aqua regia-based metal wastewater through four cycles. It could be of great potential in the practical application.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

This paper studies the use of zinc oxide nanoparticles (ZnO-NPs) synthesized using an extract of convolvulus leaves and expired ZnCl₂, as an efficient inhibitor for carbon steel corrosion in 1M HCl solution. ZnO-NPs are characterized by Fourier-transform infrared spectrophotometer (FTIR) and UV–Vis analysis. The technique of weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS) has also been used to investigate the prevention of carbon steel corrosion in 1M HCl. The results showed that the efficiency of restraint increased when the concentration of ZnO-NPs was raised to 91% and that the inhibition efficiency is still high despite its decrease at high temperature, and it acts as a mixed-type inhibitor A sample of carbon steel with the protective inhibitor layer on top was immersed for 20 hours and observed; an increase in the charge transfer resistance (Rct) and stability of the inhibitor was noticed after 6 hours. Adsorption isotherm models demonstrated that the inhibitor adsorption mechanism on the carbon steel surface followed Langmuir, more than Freundlich and Temkin, behavior. The thermodynamic parameters showed that the adsorption process is a mixed adsorption, spontaneous, and exothermic. The results illustrated that the acid medium was a strong inhibitor of carbon steel corrosion. Scanning electron microscope (SEM) showed that the ZnO-NPs formed a good protective film on the carbon steel surface.

The effects of octadecylamide of alginic acid (amidated alginate) and tetrahydrolipstatin on serum and hepatic cholesterol, and the faecal output of fat and sterols were compared in rats. Amidated alginate is a sorbent of lipids, tetrahydrolipstatin is inhibitor of pancreatic lipase. Rats were fed diets containing cholesterol and palm fat at 10 and 70 g/kg, respectively. Palm fat was provided by coconut meal. Amidated alginate at 40 g/kg diet significantly decreased serum total cholesterol, LDL and hepatic cholesterol, hepatic lipids, and increased faecal output of fat and coprostanol. Tetrahydrolipstatin at 300 mg/kg diet significantly decreased LDL cholesterol, hepatic lipids and increased faecal output of fat. The intake of feed was not significantly influenced, however the weight gains in rats fed amidated alginate was lower than in rats of the control group. Both amidated alginate and tetrahydrolipstatin modified fatty acid profile in excreta lipids. Concentrations of saturated fatty acids were decreased and that of unsaturated fatty acids were increased. Despite different mode of action, amidated alginate and tetrahydrolipstatin were equally efficient in the removing dietary fat from the body.

Faba bean (Vicia faba L) is the first grain legume in terms of hectarage, total production and foreign exchange earnings in Ethiopia. The current study was designed to evaluate effect of NPS and bio-organic fertilizers on the yield and yield components of faba bean in Debre Markos University research farm. A total of 16 treatments were made from the factorial combination of four levels NPS (0, 50, 100 and 150 kg ha-1) and four levels bio-organic fertilizer (Nil BOF (Bio(Nil)), rhizobium (Bio(IR)), 10 t ha-1 FYM (Bio(FYM)) and FYM+Rhizobium (Bio(FYM+IR))) in randomized complete block design (RCBD) with three replications. The Walki (EH 96049-2) variety, which is high yielding, moderate disease resistant and water-logging tolerant used as test crop. The result experiment showed that, plot treated with Bio(FYM+IR)+NPS100 treatment gave statically maximum effective number of tillers (2.73), maximum number of pods per plant (20.30), hundred seeds weight (76.11g), grain yield (5.62 t ha-1), biomass yield (10.94 t ha-1) and Harvest index (59.91%) than over other treatments received NPS fertilizer with and without bio-organic fertilizers. Therefore, the combined use of 100kg ha-1 NPS with 10 tha-1 FYM and rhizobium inoculation is superior for optimum production of faba bean in study area.

Ion current rectification (ICR) is the ratio of ion current by forward bias to by backward bias and is a critical indicator of diode performance. In previous studies, many attempts have been continued to improve the performance of this ICR, but there is the intrinsic problem for geometric changes that induce ionic rectification due to their fabrication problem. Additionally, the high ICR could be achieved in the narrow salt concentration range only. Here, we propose a multi-layered bipolar ionic diode based on an asymmetric nanochannel network membrane (NCNM), which is realized by soft lithography and self-assembly of homogenous-sized nanoparticles. Owing to the freely changeable geometry based on soft lithography, the ICR performance can be explored according to the variation of microchannel shape. Interestingly, very stable ICR performance can be achieved using the multi-layered 3D configuration for the bipolar diode in a broad range of salt concentrations (0.1mM ~ 100 mM). This demonstrates the promising potential of multi-layered NCNM for applications in highly concentrated electrolytes, such as biosensors, desalination, or energy harvesting.

Common buckwheat (Fagopyrum esculentum Moench) is an annual spring-emerging crop that is classified among dicotyledons, yet due to the manner of its cultivation, use, and chemical composition of seeds. The use of buckwheat straw for energy purposes, for example, for the production of second generation bioethanol might enable its wider application and increase the cost-effectiveness of tillage. In this study, we examined the usability of buckwheat straw for the production of bioethanol. We pretreated the raw material with using ionic liquids and subsequently performed enzymatic hydrolysis and alcoholic fermentation. The obtained chemometric data was analyzed using the Partial Least Squares (PLS) regression model. PLS regression in combination with the spectral analysis within near-infrared (NIR) spectrum allowed for the rapid determination of amount of cellulose in the raw material and also provided information on the changes taking place in its structure. According to our results, we obtained good results for the combination of 1-ethyl-3-methylimidazolium acetate as the ionic liquid and Cellic CTec2 and the enzymatic preparation for the pretreatment of buckwheat straw. The highest concentration of glucose following 72 hours of enzymatic hydrolysis was found to be around 5.5 g/dm3. The highest concentration of ethanol (3.31 g/dm3) was obtained with the combination of 1-butyl-3-methylimidazolium acetate for the pretreatment and the cellulase from Trichoderma reesei for enzymatic hydrolysis. In summary, the efficiency of the fermentation process is strictly associated with the pool of available fermenting sugars, and it depends on the type of ionic liquid used during the pretreatment and on the enzymatic preparation. It is possible to obtain bioethanol from buckwheat straw using ionic liquid for the pretreatment of the raw material prior to the enzymatic hydrolysis and alcoholic fermentation of the material.

The use of mixed-state ionic beams in collision dynamics investigations is examined. Using high resolution Auger projectile spectroscopy involving He-like ($1s^2\thinspace^1\!S, 1s2s\thinspace^{3,1}\!S$) mixed-state beams, the spectrum contributions of the $1s2s\thinspace^3\!S$ metastable beam component is effectively separated and clearly identified. This is performed with a technique that exploits two independent spectrum measurements under the same collision conditions, but with ions having quite different metastable fractions, judiciously selected by varying the ion beam charge-stripping conditions. Details of the technique are presented together with characteristic examples. In collisions of 4 MeV B$^{3+}$ with H$_2$ targets, the Auger electron spectrum of the separated $1s2s\thinspace^{3}S$ boron beam component allows for a detailed analysis of the formation of the $1s2s(^3\!S)nl \thinspace^2\!L$ states by direct $nl$ transfer. In addition, the production of hollow $2s2p\thinspace^{1,3}\!P$ doubly- and $2s2p^2\thinspace^2\!D$ triply-excited states, by direct excitation and transfer-excitation processes, respectively, can also be independently studied. In similar mixed-state beam collisions of 15 MeV C$^{4+}$ with H$_2$, He, Ne and Ar targets, the contributions of the $1s^2$, $1s2s\thinspace^{3,1}S$ beam components to the formation of the $2s2p\thinspace^{3,1}\!P$ states by double-excitation, $1s\rightarrow2p$ excitation and transfer-loss processes can be clearly identified, facilitating comparisons with theoretical calculations.

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

Fiber coupling efficiency is one of the key technical indicators of atmospheric laser communication, which directly affects the communication system BER. According to the optical fiber coupling efficiency model, the optical fiber coupling model under atmospheric slant link is established, and the relationship between wavelength, zenith angle, receiving aperture, altitude and coupling efficiency is studied through numerical simulation. Based on the principle of adaptive optics turbulence correction, the relationship between fiber coupling efficiency and adaptive optics order is established. A fast method for estimating the coupling efficiency based on Strehl ratio is proposed. According to the principle of laser communication system, the semi-physical simulation experimental system of atmospheric slant-range channel coupling efficiency is constructed, and the coupling efficiency test and analysis are completed.

Transient receptor potential canonical (TRPC) channels are calcium channels with diverse expression profiles and physiological implications in the retina. Neurons and glial cells of rat retinas with photoreceptor degeneration caused by retinitis pigmentosa (RP) exhibit basal calcium levels that are above those detected in healthy retinas. Inner retinal cells are the last to degenerate and are responsible for maintaining the activity of the visual cortex even after complete loss of photoreceptors. We considered the possibility that TRPC1 and TRPC5 channels might be associated with both the high calcium levels and the delay in inner retinal degeneration. TRPC1 is known to mediate protective effects in neurodegenerative processes, while TRPC5 promotes cell death. In order to comprehend the implications of these channels in RP, the co-localization and subsequent physical interaction between TRPC1 and TRPC5 in healthy retina (Sprague-Dawley rats) and degenerating (P23H-1, a model of RP) retina were detected by immunofluorescence and proximity ligation assays. There was an overlapping signal in the innermost retina of all animals where TRPC1 and TRPC5 physically interacted. This interaction increased significantly as photoreceptor loss progressed. Both channels function as TRPC1/5 heteromers in the healthy and damaged retina, with a marked function of TRPC1 in response to retinal degenerative mechanisms. Furthermore, our findings support that TRPC5 channels also function in partnership with STIM1 in Müller and retinal ganglion cells. These results suggest that increase in TRPC1/5 heteromers may contribute to slowing of the degeneration of the inner retina during the outer retinal degeneration.

This retrospective begins with Galvani's experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions in the fields of physical chemistry in the second half of the 19th century (Nernst’s equilibrium potential, based on the work of Wilhelm Ostwald, Max Planck's ion electrodiffusion, Einstein's studies of Brownian motion), which led Bernstein to propose his membrane theory in the early 1900s as an explanation of Galvani’s findings and cell excitability. These processes were fully elucidated by Hodgkin and Huxley in 1952, by detailing the ionic basis of resting and action potentials, but without addressing the question of where these ions passed. The emerging question of the existence of ion channels, widely debated over the next two decades, was finally accepted and, a decade later, many of them began to be cloned. This led to the possibility of modelling the activity of individual neurons in the brain and then of simple circuits. Taking advantage of the remarkable advances in computer science in the new millennium, together with a much deeper understanding of brain architecture, more ambitious scientific goals were dreamed of to understand the brain and how it works. The retrospective concludes by reviewing the main efforts in this direction, namely the construction of a digital brain, an in silico copy of the brain that would run on supercomputers and behave just like a real brain.

Chronic pain is a significant health problem worldwide. Recent evidence has suggested that dysfunctional states of the ventral hippocampus, including decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity and persistent nociceptive hypersensitivity in humans and rodents, respectively. But the molecular mechanisms underlying hippocampal modulation of pain remain poorly elucidated. In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. Reduced sag potential and firing rate of action potentials were observed in vCA1 pyramidal neurons from CFA-injected mice. Moreover, the expression of HCN2, but not HCN1, in vCA1 decreased in mice injected with CFA. HCN2 knockdown in vCA1 pyramidal neurons induced thermal hypersensitivity, whereas over-expression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggests that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.

Rainfall retrieval using geostationary satellites provides critical means to the monitoring of extreme rainfall events. Using the relatively new Himawari 8 meteorological satellite with three times more channels than its predecessors, the deep learning framework of “convolutional autoencoder” (CAE) was applied to the extraction of cloud and precipitation features. The CAE method was incorporated into the Convolution Neural Network version of the PERSIANN precipitation retrieval that uses GOES satellites. By applying the CAE technique with the addition of Residual Blocks and other modifications of deep learning architecture, the presented derivation of PERSIANN operated at the Central Weather Bureau of Taiwan (referred to as PERSIANN-CWB) expands four extra convolution layers to fully use Himawari 8’s infrared and water vapor channels, while preventing degradation of accuracy caused by the deeper network. The development of PERSIANN-CWB was trained over Taiwan for its diverse weather systems and localized rainfall features, and the evaluation reveals an overall improvement from its CNN counterpart and superior performance over all other rainfall retrievals analyzed. Limitation of this model was found in the derivation of typhoon rainfall, an area requiring further research.

Simultaneous extraction of trypsin inhibitors and soy isoflavones from soybean meal was investigated using the non-destructive phytochemical extraction process, namely aqueous micellar system. The ethoxylated aliphatic alcohols Genapol X-080, Tergitol 15-S-7, and Tergitol 15-S-9, all non-toxic and biodegradable surfactants, were assessed as potential extractants. A Box-Behnken multifactorial design with the application of the Derringer desirability was used to determine the conditions that maximized the trypsin inhibitors and isoflavone extraction while minimizing the protein extraction. The optimum condition of 5% m/m of surfactant in 50 mM aqueous sodium citrate solution pH 4.5, at 45 °C for 45 min, was established for the three surfactants. The novel methodology would allow the extraction of the main soybean antinutritional factors, trypsin inhibitors, and the valuable isoflavones, preserving the nutritional quality of the treated material. This represents a sustainable alternative methodology for industrial purposes due to its low cost, biodegradability, non-toxicity, and easy scaling up.

Cholesterol is a lipid-derived substance found in lipoproteins and cell membranes. It is also one of the main sources for the production of bile acids, vitamin D, and steroid hormones. Today, foods are evaluated by consumers not only according to their taste and nutritional content but also according to their effects on consumer health. For example, many consumers choose foods according to their cholesterol level. The cholesterol in the food can directly affect the blood cholesterol level when consumed, which can lead to cardiovascular diseases. High levels of cholesterol can lead to diet-related human diseases such as cardiac arrest, paralysis, type II diabetes cerebral hemorrhage. In societies with high living standards, interest in and consumption of foods that lower or have low cholesterol levels have increased recently. Accordingly, efforts to increase the variety of foods with reduced cholesterol levels are on the rise. This has indirectly insulted in accurate measurement of cholesterol levels in blood and food being of great importance. Classical chemical, enzymatic, colorimetric, polarographic, chromatographic, spectrophotometric methods, and enzymatic, nonenzymatic, and electrochemical sensors and biosensors are used for the determination of cholesterol in foods. The purpose of this review is to reveal and explore current and future trends in cholesterol detection methods in foods. The review will summarize the most appropriate and standard methods for measuring cholesterol in biological components and foods.

Approximately one-third of mankind is chronically exposed to the carcinogenic aflatoxin M1 contained in milk and dairy products and there is no ready to use procedure for decontamination purposes applicable in milk technology. Since β-cyclodextrin is frequently used in food industry, its effect on aflatoxin M1 concentration was investigated during cholesterol removal. So, milk samples were spiked with aflatoxin M1 at the average level 0.89 µg/kg and cholesterol removal was carried out by 2.0% (w/w) β-cyclodextrin addition. As found, average cholesterol concentration decreased by 92.3% while aflatoxin M1 concentration decreased to 0.53 µg/kg, i. e. by 39.1% after the treatment. The procedure itself is easy, inexpensive, and ready to use in milk processing technology on current production lines without any investments, thus fully applicable with a high potential of full aflatoxin M1 milk decontamination efficiency and such way to strengthen considerably the food safety issues associated with milk and dairy products on global level.

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m²) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

The 2015 Dietary Guidelines for Americans recommends that individuals should eat as little dietary cholesterol as possible. However, current dietary cholesterol intake and its food sources have not been well-characterized. We examined dietary cholesterol intake by age, sex, race, and food sources using 24-hour dietary recall data from a nationally representative sample of 5047 adults aged 20 years or older who participated in NHANES (2013–2014 survey cycle). We also reported trends in cholesterol intake across the past 7 NHANES surveys. Mean dietary cholesterol intake was 293 mg/day (348 mg/day for males and 242 mg/day for females) in the 2013–2014 survey cycle; 39% of adults had dietary cholesterol intake above 300 mg/day (46% for males and 28% for females). Meat, eggs, grain products, and milk were the highest four food sources of cholesterol, contributing to 96% of the total consumption. Both average cholesterol intake and food source varied by age, sex, and race (each p < 0.05). Mean cholesterol intake of the overall population had been relatively constant at ~290 mg/day from 2001–2002 to 2013–2014 (p-trend = 0.98). These results should inform public health efforts in implementing dietary guidelines and tailoring dietary recommendations.