Leishmaniases are zoonotic vector-borne diseases caused by a wide variety of Leishmania species with complex transmission cycles involving different reservoirs, potential new hosts and vectors. Similarly, to other eukaryotes, Leishmania use released extracellular vesicles (LEVs) to play important initial interactions that are crucial to modulate the subsequent systemic immune response on the establishment of infection in humans and other important hosts like dogs. Recent studies in endemic areas of Brazil concluded that canine infections were predominantly due to L. amazonensis and not restricted to L. infantum (syn. Leishmania chagasi). Under these premises, the diagnosis of canine leishmaniasis needs to be improved, including the identification of current etiological agent, the clinical differential diagnosis and the histopathologic features. In this way, the dual aim of that study is to register collected observations for the diagnosis of natural canine infections and to insert in vitro results in the field of LEVs that still research gaps to be filled to understand the mechanisms and biological aspects involving the parasite-host interactions. Therefore, the future studies of Parasitology research for both of these fields are very important for the interventions for the prevention, control, elimination and eradication worldwide.

In general, a superconductor has zero resistance, although it requires significant refrigeration or high pressures with high manufacturing costs, which prevents it into practical applications. In other words, solving these issues implies main superconducting researches. To solve these problems, this paper describes a new type of superconductivity, which is independent for temperatures and which operates without pressures. The principles of the presented system are as follows:First a voltage source, a current source and a load are connected in series. Then, the voltage of the voltage source is adjusted to balance the voltage of the load. Under this condition, the balance of the two voltages provides a zero voltage between the taps of the current source and the generated current from the voltage source becomes zero because of the internal infinite resistance of the current source. As a result, the electric powers generated by the two sources are zero, and therefore, the load cannot generate Joule heating because of energy conservation. However, the current from the current source (not the voltage source) is not zero; therefore, we can predict that the resistance of the load must be zero. As a theory, we derived a new electric field and transient attractive force, which result in a very short coherence of an electron pair because there is not the Coulomb repulsive force due to the existence of the above transient attractive force. Note that both the forces are derived by the Poisson equation, which implies that they cannot be compatible. Therefore, the pair combination energy from spins becomes extremely strong, which is not destroyed by the normal heat energy. Moreover, every center-of-mass motion of electron pair results in the Bose-Einstein condensation and the macroscopic wave function, which produces the London equation (i.e., the Meissner effect). Moreover, by introducing the equivalent circuit, this paper conducted numerical calculations. As a result, we could derive numerically zero resistance and responses for additional static magnetic fields as a discharged current, which implies the Meissner effect. Note that this paper has prepared Appendix section, which provides a guide to reproduce actual experiments and preliminary experimental results. These results in the Appendix indicate the zero resistances and Meissner effects.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Thyroid hormones, their metabolites and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This review focusses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in prevention or treatment of obesity and related metabolic conditions.

The dispersive and polar properties of materials, and especially of polymers and copolymers play an important role in several engineering applications implying their surfaces and interfaces. The surface energetic properties of poly(styrene-co-butadiene) have never been studied. We proposed in this study an accurate determination of such properties by using the inverse gas chromatography (IGC) at infinite dilution. Background: The IGC surface technique led to the dispersive and polar properties of poly(styrene-co-butadiene) rubber (SBR) by adsorption of organic solvents at various temperatures. Methods: Our new methodology based on the thermal Hamieh model and the London dispersion interaction energy was used to determine the London dispersion surface energy, the polar acid-base surface energy, and the Lewis acid-base properties of the copolymer. Results: The different surface energy parameters of the SBR were obtained as a function of temperature from the chromatographic measurements. Conclusions: The dispersive and polar free energies of adsorption of the various n-alkanes and polar molecules on poly(styrene-co-butadiene) were determined at different temperatures. A decrease of the London dispersive surface energy and the polar Lewis acid-base surface energies of SBR was highlighted when the temperature increased. It was showed a Lewis amphoteric character of poly(styrene-co-butadiene) with a highest basic constant 10 times larger than its acidic constant.

Vanadium(IV) chalcogenide materials are of increasing interest for use in catalysis and energy conversion-related applications. Since no ternary compounds are yet known in the V–Se–Te system, we studied ternary VwSeyTe2–y (w = 1.10, 1.13; y = 0.42, 0.72) phases crystallizing in space group P3m1 (no. 164). Two single-crystal specimens with differing compositions of a solid solution were obtained using the ceramic method. All products were characterized by either single-crystal or powder X-ray diffraction. The lattice parameters increase with rising tellurium content in accordance to the larger ionic radius of the tellurium anion compared to selenium. The chemical compositions were confirmed by energy dispersive X-ray spectroscopy. Further, magnetic measurements revealed mostly antiferromagnetic properties. Simultaneous differential scanning calorimetry/thermogravimetric analyses in nitrogen atmosphere showed endothermic decomposition accompanied by the formation of VN. The results of this work can serve as a basis for the synthesis of new phases in the V–Se–Te and related vanadium chalcogenide systems.

The cytoplasmic membrane is the fundamental component of all living cells, which participates in various physiological processes, such as material exchange, stress response, cell recognition, signal transduction, cellular immunity, apoptosis, pathogenicity, etc. The normal function of a cytoplasmic membrane requires stable organization of transmembrane protein-lipid microdomains, transmembrane protein-cell wall microdomains, and cytoskeleton-transmembrane protein microdomains. Here, we review the mechanisms and functions of various membrane lipid components, fatty acid content and saturation, membrane curvature, and cell wall and cytoskeleton in plasma membrane homeostasis affecting the pathogenicity of pathogenic fungi. Pathogenic fungi maintains plasma membrane homeostasis and contributes to fungal virulence by maintaining plasma membrane assembly, structural and functional integrity of pathogenic fungi at various stages of cell development through interactions among lipid components of cytoplasmic membranes, transmembrane proteins, cytoskeleton and cell wall components, etc.

The surface thermodynamic properties of polymers and copolymers modified by supramolecular structures are very used in several industrial processes, such as selective adsorption, paints, coatings, colloids, and adhesion applications. Background: Inverse gas chromatography at infinite dilution was proved to be the best technique to determine the surface properties of solid surfaces by studying the adsorption of some model polar and non-polar organic molecules adsorbed on solid surfaces by varying the temperature. Methods: The retention volume of adsorbed solvents is a precious parameter to obtain the London dispersive and polar free energies and the London dispersive surface energy of styrene–divinylbenzene copolymer modified by supramolecular structure of melamine using the Hamieh thermal model and our new methodology consisting in the separation of the two polar and dispersive free energy of interaction. This led to the determination of the polar acid and base surface energy, and the Lewis’s acid-base constants of the various solid materials. Results: all surface energetic properties of styrene–divinylbenzene copolymer modified by melamine at different percentages were determined as a function of temperature, following our new methodology. Conclusions: It was observed that the styrene–divinylbenzene copolymer exhibited the highest London dispersive surface energy which decreased when the melamine percentage increased. All materials presented higher Lewis’s basicity and this Lewis’s basicity increased with the percentage of melamine.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of about 10,000 different soluble and membrane proteins in humans. It involves co- or post-translational targeting of precursor polypeptides to the ER and their subsequent membrane insertion or translocation. So far, three pathways for ER targeting of precursor polypeptides plus four pathways for ER targeting of mRNAs were described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the precursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting various peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in targeting and, putatively, inserting monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose if this pathway may play a more general role in ER protein targeting, i.e. represents a fourth pathway for ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach, which involves label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells and differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3-clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices and belonging to the secretory pathway were also negatively affected by PEX3-deficiency, which may suggest compromised collagen biogenesis as a hitherto unknown contributor to organ failures in the respective Zellweger patients.

Glycosyl inositol phospho ceramides (GIPCs) are the major sphingolipids on earth as they account for a considerable fraction of the total lipids in plants and fungi which in turn represent a large portion of the biomass on earth. Despite their obvious importance, GIPC analysis remains challenging due to the lack of commercial standards and automated annotation software. In this work, we introduce a novel GIPC glycolipidomics workflow based on reversed-phase ultra-high pressure liquid chromatography coupled to high-resolution mass spectrometry. For the first time, automated GIPC assignment was performed using the open-source software Lipid Data Analyzer based on platform-independent decision rules. Four different plant samples (salad, spinach, raspberry, strawberry) were analyzed and revealed 64 GIPCs based on accurate mass, characteristic MS2 fragments and matching retention times. Relative quantification using lactosyl ceramide for internal standardization revealed GIPC t18:1/h24:0 as the most abundant species in all plants. Depending on the plant sample, GIPCs contained mainly amine, N-acetylamine or hydroxyl residues. Most GIPCs revealed a Hex-HexA-IPC core and contained a ceramide part with a trihydroxylated t18:0 or t18:1 long chain base and hydroxylated fatty acid chains ranging from 16 to 26 carbon atoms in length (h16:0 – h26:0). Interestingly, six GIPCs containing t18:2 were observed in raspberry, which was not reported so far. The presented workflow supports the characterization of different plant samples by automatic GIPC assignment potentially leading to the identification of new GIPCs. For the first time, automated high‑throughput profiling of these complex glycolipids is possible by liquid chromatography-high-resolution mass spectrometry and subsequent automated glycolipid annotation based on decision rules.

Porter's diamond model was used because it is an index in the field of competitiveness and increasing the index of competition in the international arena. In order to measure actions in the field of commerce and marketing trends and its compliance with Porter's diamond model, an organization named Isfahan Chamber of Commerce, Industries, Mines and Agriculture was selected from among the existing non-governmental organizations in Iran. This non-governmental organization, having different departments has members and subgroups related and influential in the field of commerce and marketing. In order to answer the question raised in this research, that is, to determine the position of the Isfahan Chamber of Commerce, Industries, Mines and Agriculture in Porter's diamond model, by referring to this organization in person, the available documents, information and data available in a descriptive-survey manner. It was reviewed until October 2022. All key activities and works performed in this organization in the period from March 2019 to March 2022 were identified and separated according to the internal factors of Porter's Diamond model. Finally, the credibility and effectiveness of this non-governmental organization as a link between the private sector and the government was measured in the Porter's diamond model.

The thermal surface properties of graphenes and carbon materials are of crucial importance in chemistry of materials, chemical engineering, and many industrial processes. (1) Background: The determination of these surface properties is carried out using inverse gas chromatography at infinite dilution which leads to the retention volume of organic solvents adsorbed on solid surfaces. This experimental and fundamental parameter actually reflects the surface thermodynamic interactions between injected probes and solid substrates. (2) Methods: The London dispersion equation and the Hamieh thermal model were used to quantify the London dispersive and polar surface energy of graphenes and carbon fibers as well their Lewis acid-base constants by introducing the coupling amphoteric constant of materials. (3) Results: The London dispersive and polar acid-base surface energies, the free energy of adsorption, the polar enthalpy and entropy, and the Lewis acid-base constants of graphenes and carbon materials were determined. (4) Conclusions: it was showed that graphene exhibited the highest values of London dispersive surface energy, polar surface energy, and Lewis’s acid-base constants. These highest characteristics of graphene justify its great potentiality and uses in many industrial applications.

Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid which is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and formation of products with photosensitizing properties. The aim of this study was to test on cultured human retinal pigment epithelial cells ARPE-19 the (photo)cytotoxic potential of partly oxidized docosahexaenoate and its effect on the formation of lipofuscin from phagocytosed photoreceptor outer segments (POS). The results demonstrate that the cytoprotective effects of docosahexaenoate do not counteract the deleterious effects of its oxidation products leading to the concentration-dependent loss of cell metabolic activity, which is exacerbated by concomitant exposure to visible light. Partly oxidized docosahexaenoate does not cause permeability of the cell plasma membrane but does cause apoptosis. While vitamin E can provide partial protection from the (photo)toxicity of partly oxidized docosahexaenoate, zeaxanthin undergoes rapid photodegradation and can exacerbate the (photo)toxicity. Feeding cells with POS enriched in partly oxidized docosahexaenoate results in a greater accumulation of intracellular fluorescent lipofuscin than in cells fed POS without the addition. In conclusion, partly oxidized docosahexaenoate increases the accumulation of lipofuscin-like intracellular deposits, is cytotoxic, and its toxicity increases during exposure to light.

The swift progress in low-dimensional nanocarbons, specifically in the realm of the authentic one-dimensional carbon chain featuring sp¹ hybridization, has unveiled exciting prospects for integrating them into cutting-edge technologies across diverse industries. To fully harness their potential, precise control over the growth process is necessary to obtain desired nanostructure and functionality. However, optimizing properties through traditional approaches has been challenging due to complex interactions. To address this, we implement a focused data-driven strategy for nanocarbon inverse design by leveraging a state-of-the-art data-driven nanocarbon genome approach (NCGA). By uncovering relationships between growth parameters and resultant traits, this serves as an expedient catalyst in engineering nanostructures with tailored attributes. We introduce an extensive array of technological approaches aimed at precisely controlling the growth process. These methods encompass stimulating and precisely adjusting synergistic effects, coordinating atomic vibrations at a collective level through the implementation of multilayer nano-interfaces, harnessing the potential of active screen plasma surface engineering, utilizing nano-patterning and allotropic phase transformations, incorporating heteroatom doping, and effectively directing self-assembly. These aim to unlock nanomaterials' latent potential and reveal novel neural pathways within the data-driven NCGA, enhancing its predictive capabilities. Specifically, triggering self-organization during growth can potentially unlock previously unexplored neural pathways. The data-driven NCGA offers a paradigm shift, accelerating discovery and design of nanocarbons with optimized, application-specific properties.

The aim of the present work is to explore a different non-traditional approach to higher dimensional spacetime which differs from the usual approaches such as large extra space dimensions, warped extra space dimensions and multiple extra time dimensions. This approach will be referred to as "Dynamic" higher dimensional spacetime. By this term will be introduced a new kind of higher dimensional spacetime (more than the usual 3+1 dimensions), which behaves dynamically in the sense that time is not a fixed dimension but is the extra plus one dimension to the spatial dimensions of the phenomenon we are studying. For a higher dimensional phenomenon, the lower dimensional time will behave as space and the new time will be a plus one dimension, meaning if we study a 3-dimensional phenomenon then time is the usual 4th dimension but if we are studying a 4-dimensional phenomenon then its time will be an extra 5th dimension and for this phenomenon the 4th dimension will behave as space. All spatial dimensions are indistinguishable from each other and behave in the exact same way, which means that the important parameter is not the dimension we are studying (for example the 4th or the 5th) but the number of dimensions in which a phenomenon can interact and how higher dimensional phenomena interact with lower ones. This non-traditional approach to higher dimensional spacetime may appear confusing at first but will become clearer in the rest of the paper. For this reason, we will first associate the time dimension with propagation relative to space dimensions and change orthogonal to them in order to give the reader a better intuition. Following that, we will describe how higher - dimensional phenomena would appear to us, the 3 - dimensional observer and try to set some guidelines on how we should mathematically model higher - dimensional phenomena in order for us to make accurate predictions of their behaviour. Then we will express the general framework of a "Dynamic" higher - dimensional spacetime and turn our gaze to 4+1 – dimensional phenomena. We will explore how a mass term arises for 4 – dimensional waves by generalizing the frequency – speed – wavelength relation of 3D waves and give a basic description on a possible way to describe a 4+1 – dimensional disturbance in a scalar Energy Field in order to make accurate predictions on our 3+1 dimensional plane. In this framework we will derive the Klein – Gordon equation by generalizing the wave equation and ignoring all lower than 4+1 - dimensional disturbances and compere our mass term findings with the Klein – Gordon equation mass term and with results from gravity – induced quantum interference experiments. Lastly, we will describe how a "Dynamic" 5 - dimensional spacetime would appear in a 3D observer and examine whether our findings are compatible with quantum mechanics and the special theory of relativity.

Leishmaniases are zoonotic vector-borne diseases caused by a wide variety of Leishmania species with complex transmission cycles involving different reservoirs, potential new hosts and vectors. Similarly, to other eukaryotes, Leishmania release extracellular vesicles (LEVs) to play important initial interactions that are crucial to modulate the subsequent systemic immune response on the establishment of infection in humans and others hosts like dogs. Recent studies in endemic areas of Brazil concluded that canine infections were predominantly due to L. amazonensis and not restricted to L. infantum (syn. Leishmania chagasi). Under these premises, the diagnosis of leishmaniasis needs to be improved with the identification of current etiological agent and the histopathologic features, highlighting the differential diagnosis and the molecular components of LEVs. In this way, the dual aim of that study is to register collected observations of natural canine infections, enhancing the relevance of differential diagnosis in companion animals and inserting in vitro results in the field of LEVs that still research gaps to be filled to understand the mechanisms and biological aspects involving the parasite-host interactions. Therefore, improve these studies of Parasitology research is important for diagnostic, prognostic, treatment advances and continuing need for global prevention, control, elimination/eradication of these parasitic infections.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthetic system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remain largely unknown thus far. Based on the ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator capable of promoting wound healing and regenerative functions of mesenchymal stem cells (MSCs), en-dothelial cells, and macrophages. The third-degree (3o) burn healing and regenerative functions of MSCs are also enhanced by ACgel1, an arginine and chitosan-based protein-mimic hybrid hy-drogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporates PreM1 and MVFs into ACgel1 via optimal design and fabrication is capable of delivering PreM1 to 3o burn wounds at least up to 7 days post-burn (dpb), and of scaffolding and delivering MVFs, which promoted 3o burn the healing in mice, including vascularization and collagen formation. The re-epithelization and closure of 3o burn wounds were promoted by ACgel1, MVFs, PreM1, MVFs-ACgel1, PreM1-ACgel1, or PreM1-MVFs-ACgel1 at certain time-point(s) while PreM1-MVFs-ACgel1 was most effective. The PreM1-ACgel1 and MVFs-ACgel1 also promoted blood vessel regeneration of the 3o burns. These PreM1- and/or MVFs- functionalized ACgel1 have nonexistent or minimal graft-donor requirements and are promising adjuvant therapies for overcoming the drawbacks of current skin grafting or substituting for treating severe deep burns.

This work is a physical review, with elements of additions and thinning, on the methods of theoretical studies of nonlinear electrophysical phenomena in crystals with ion-molecular chemical bonds (CIMB). Crystals of this class include ionic dielectrics (characterized by high ionic conductivity), layered crystals, a special case of which are hydrogen-bonded crystals (HBC), defined as proton semiconductors and dielectrics (PSD).A scientific review (comparative analysis and justification of various approximations) was carried out on the methods of constructing and solving a generalized quasi-classical kinetic equation describing the mechanism of nonlinear relaxation polarization and conductivity processes in dielectric materials with ion-molecular chemical bonds (a special case is hydrogen-bonded crystals (HBC)) in a wide temperature range (1-1550 K) and polarizing field strengths (0.1-1000 V/m) at alternating field frequencies of the order of 1 kHz - 1000 MHz. The most important variant of the equations of the kinetic theory of dielectric relaxation in this work is the generalized non-linear by polarizing field quasi-classical kinetic equation of ionic (in HBC, proton) relaxation, based on the particle number balance equation (conductivity ions) in potential wells and having (in these models) the meaning of the ion current continuity equation (in HBC, protons), solved by the method of successive approximations by decomposition into infinite power series by degrees of a small dimensionless comparison parameter. It was found that in the area of ​ ​ weak fields (0.1-1 MW/m) at temperatures T = 50 - 550 K, for a number of ionic dielectrics (including HBC and similar dielectric properties and lattice structure) the generalized quasi-classical kinetic equation transforms to the linearized Fokker – Planck equation and, in the region of low (50-100K) and higher temperatures (250-550 K) begin to manifest non-linear polarization effects due to respectively proton tunneling (in the case of HBC) and volume charge relaxation (in the case of the HBC and for a wider class of ionic dielectrics). At ultra-low (1-10 K) temperatures in the region of weak fields (0.1-1 MW/m) and ultra-high temperatures (550-1550 K) in the region of strong fields (10-1000 MW/m), the contribution of this kind of effects to polarization is significantly enhanced. The effect of nonlinearities on relaxation times for microscopic acts of proton transitions across a potential barrier (assumed to be parabolic) is investigated. Nonlinear effects at volume-charge polarization in the hydrogen-bonded crystals (HBC) in alternating electric field, in radio frequency range are investigated. From the solution of the system of nonlinear Fokker-Planck equations (macroscopic kinetic equation) and Poisson, with blocking electrodes, using Fourier series, a recurrent (convenient for use in any approximation of perturbation theory) expression is constructed for complex amplitudes of relaxation modes of volumetric charge. Complex dielectric permittivity (CDP) is calculated as a series decomposition over even frequency harmonics of a variable field. The effect of quantum proton transitions and polarizing field parameters (strength, frequency) on the nonlinear properties of proton semiconductors and dielectrics has been established.