Wild-type p53 cancer therapy-induced senescent cells frequently engulf and degrade neighboring ones inside a massive vacuole in their cytoplasm. After clearance of the internalized cell, the vacuole persists, seemingly empty, for several hours. Despite large vacuoles being associated with cell death, this process is known to confer a survival advantage to cancer engulfing cells, leading to therapy resistance and tumor relapse. Previous attempts to resolve the vacuolar structure and visualize their content using dyes were unsatisfying for lack of known targets and ineffective dye penetration and/or retain. Here, we overcame this problem by applying optical diffraction tomography and Raman spectroscopy to MCF7 doxorubicin-induced engulfing cells. We demonstrated a real ability of cell tomography and Raman to phenotype complex microstructures, such as cell-in-cells and vacuoles, and detect chemical species in extremely low concentrations within live cells in a completely label-free fashion. We show that vacuoles had a density indistinguishable to the medium, but were not empty, instead contained diluted cell-derived macromolecules, and we could discern vacuoles from medium and cells using their Raman fingerprint. Our approach is useful for the non-invasive investigation of senescent engulfing (and other peculiar) cells in unperturbed conditions, crucial for a better understanding of complex biological processes.

Background: Proteins targeted by the Ubiquitin Proteasome System (UPS) are identified for degradation by the proteasome, which has been implicated in the development of neuro-degenerative diseases. Major histocompatibility complex (MHC) molecules present peptides broken down by the proteasome and are involved in neuronal plasticity, regulating synapse number and axon regeneration in the central or peripheral nervous system during develop-ment and in brain diseases. The mechanisms governing these effects are mostly unknown, but evidence from different compartments of the cerebral cortex indicates the presence of im-mune-like MHC receptors in the central nervous system. Methods: We have used human induced pluripotent stem cells (iPSC) differentiated to neural stem cells and then to motor neurons as a developmental model to better understand the structure of the proteasome in developing motor neurons. We perform a proteomic analysis of starting human skin fibroblasts, their matching iPSC, differentiated neural stem cells and motor neurons that highlighted significant differences in the constitutive proteasome and immunoproteasome subunits during development towards motor neurons from iPSC. Results: Proteomic analysis showed that the catalytic proteasome subunits expressed in fi-broblasts differ to those in neural stem cells and motor neurons. Western blot analysis con-firmed the proteomic data, particularly the decreased expression of Beta5i (PSMB8) subunit immunoproteasome. Conclusion: The constitutive proteasome subunits are upregulated in iPSC from HFF and the immunoproteasome subunit beta 5i expression is higher in MN than NSC suggesting a im-munoproteasome phenotype in MN. The immunoproteasome may have implications on motor neuron development and neurodevelopmental diseases that warrants further investi-gation.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

Underwater robotics equipped with visual detection systems have the function of detecting un-derwater artifacts, which is of great significance to deep-sea archaeology. Underwater artifacts are located in complex environments with poor imaging conditions, and the targets have chal-lenging problems such as breakage, stacking, and sediment burial, which causes the marine cul-tural target detection failures. To solve these problems, this paper proposes an underwater cul-tural target detection algorithm based on the deformable deep aggregation network model for underwater robotics exploration. To fully extract the target feature information of underwater targets in complex environments, this paper designs a multi-scale deep aggregation network with deformable convolutional layers. Besides, the BAM attention module is designed for fea-ture optimization, which enhances the potential feature information of the target while weak-ening the background interference information. Finally, the target prediction is achieved through feature fusion at different scales. The proposed algorithm has been extensively validat-ed and analyzed on the collected underwater artifact datasets, and the precision, recall, and mAP of the algorithm have reached 93.1%, 91.4%, and 92.8%, respectively. In addition, the present al-gorithm has been practically deployed on the underwater robotics. In the deep-sea tests, the ar-tifact detection frame rate reaches up to 19 fps, which satisfies the real-time target detection。

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

This work investigates a new nanostructured gas-diffusion-layer (nano-GDL) to improve performance of air-cathode Single-Chamber-Microbial-Fuel-Cells (a-SCMFCs). The new nano-GDLs improves the direct oxygen-reduction-reaction by exploiting the best of nanofibers from electrospinning in terms of high surface ratio to volume and high porosity, and laser-based processing to promote adhesion. Nano-GDLs by electrospinning were fabricated directly collecting two nanofibers mats on the same carbon-based electrode, acting as the substrate. Each layer was designed with a specific function: water resistant, oxygen permeable polyvinylidene-difluoride (PVDF) nanofibers served as a barrier to prevent water-based electrolyte leakage, while an inner layer of cellulose nanofibers was added to promote oxygen diffusion towards the catalytic sites. The maximum current density obtained for a-SCMFCs with the new nano-GDLs is (132.2 ± 10.8) mA m^-2, and it doubles the current density obtained with standard PTFE-based GDL (58.5 ± 2.4 mA m^-2), used as reference material. The energy recovery (EF) factor, i.e. the ratio of the power output to the inner volume of the device, was then used to evaluate the overall performance of a-SCMFCs. a-SCMFCs with nano-GDL provided an EF value of 60.83 mJ m^-3: one order of magnitude higher than the value of 3.92 mJ m^-3 obtained with standard GDL

Fusarium wilt diseases severely influence the growth and productivity of numerous crop plants. The consortium of antagonistic rhizospheric Bacillus strains and quercetin were evaluated imperatively as a possible remedy to effectively manage the Fusarium wilt disease of tomato plants. The selection of Bacillus strains was made based on in-vitro antagonistic bioassays against Fusarium oxysporum f.sp. lycoprsici (FOL). Whereas, quercetin was selected after screening a library of phytochemicals during in-silico molecular docking analysis using tomato LysM receptor Kinases “SILKY12” based on its dual role in symbiosis and plant defense responses. After the selection of test materials, pot trials were conducted where tomato plants were provided consortium of Bacillus strains as soil drenching and quercetin as a foliar spray in different concentrations. The combined application of consortium () and quercetin (1.0 mM) reduced the Fusarium wilt disease index up to 69% also resulting in increased plant growth attributes. Likewise, the imperative application of the Bacillus consortium and quercetin (1.0 mM) significantly increased total phenolic contents and activities of the enzymes of the phenylpropanoid pathway. Non-targeted metabolomics analysis was performed to investigate the perturbation in metabolites. FOL pathogen negatively affected a range of metabolites including carbohydrates, amino acids, phenylpropanoids, and organic acids. Thereinto, combined treatment of Bacillus consortium and quercetin (1.0 mM) ameliorated the production of different metabolites in tomato plants. These findings prove the imperative use of Bacillus consortium and quercetin as an effective and sustainable remedy to manage Fusarium wilt disease of tomato plants and to promote the growth of tomato plants under pathogen stress conditions.

The oscillation of an elastically mounted rigid cylinder excited by steady fluid flow is investigated. Regarding the nonlinearity of real practical structures like marine risers and the stay cable of a long-span bridge, the dynamic behavior of the circular cylinder is described by double Duffing equations and the aerodynamic force performance of the wake flow is expressed by wake oscillator equation. Unlike previous studies, in the present investigation, attention is focused on coupling the wake oscillator equations, taking into account quadratic terms. Following this approach, the cylinder's combined cross-flow and in-line Vortex-Induced Vibrations (VIV) are modeled more accurately. Empirical coefficients are adjusted through comparison with previous credible experimental studies and the effects of changing coefficients of the quadratic terms on major VIV parameters are investigated. The oscillating amplitude calculated by the present model is close to that of the experiment. The relative error of results obtained by the present coupled model is lower than the previous model. Moreover, the present model successfully predicts the moving trajectories of a circular cylinder under VIV in a figure-of-eight shape.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, which is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved by Newmark-β method combined with Newton-Raphson iterative method. Furthermore, the rain-flow counting method and Miner's linear fatigue cumulative damage theory were used for wind induced fatigue damage assessment. Finally, a two-span TC-PTS is selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment are analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. With the increase of wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increase, and their degree of increase shows a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable is greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor is less affected by wind direction angle, and both are more significantly affected by the wind speed.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

Legumes play a significant role in the alleviation of food insecurity, maintaining soil fertility and achieving sustainable crop production under adverse environmental conditions. The increased demand in legume production contemplates that attention on the genetic improvement of these crops through various means such as genetic engineering and mutation breeding should take a centre stage in global agriculture. Therefore, this paper provides succinct analysis of currently available literature on morphological and physiological traits in polyploidised leguminous plants to counter the adverse effects of drought stress. The effects of colchicine on various morphological and physiological traits of polyploidised legumes compared to their diploid counterparts were examined. Numerous reports revealed variations in these traits such as improved root and shoot growth, plant biomass, chloroplastidic content, protein, RNA and DNA. The differences observed were also associated with the strong relationship between plant ploidy-induction and colchicine application. Furthermore, the analysis indicated that polyploidisation remains dose-dependent, and may be achievable at a shorter space of time as this antimitotic chemical interferes with chromosome separations in somatic plant cells. The efficiency of this process also depends on the advancement of treatment conditions (in vitro, in vivo or ex vitro) and successful regeneration of polyploidised plants for adaptation under drought stress conditions. As such, the improvement in metabolite profile and other essential growth characteristics serves as a clear indication that induced polyploidy needs to be further explored to confer resilience to environmental stress, and improve crop yield under drought stress conditions in leguminous plants.

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. A doping-induced and concentration-dependent phase transition in ZrO₂ under the influence of Y₂O₃ was discovered, due to which the position of the Fermi level changes and the energy gap decreases. It has been established that, not only for pure systems but including those doped with Y₂O₃, the main contribution to the formation of the conduction band is made by the p-states of electrons. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of -1.22 eV, as well as by the method of molecular chemisorption with an energy of - 0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of -1.84 eV. Dissociative adsorption of water occurs at an energy of -1.23 eV, near the yttrium atom. The results show that ab initio approaches are able to describe the mechanism of doping-induced phase transitions in (ZrO₂+Y₂O₃)-like systems, based on which it can be assumed that DFT calculations can also flawlessly evaluate other physical and chemical properties of YSZ, which have not yet been studied quantum chemical research. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation and can be used in designing humidity-to-electricity converters and creating solid oxide fuel cells based on ZrO₂.

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. The doping-induced and concentration-dependent phase transition of zirconium dioxide under the influence of yttrium oxide was studied, after which the position of the Fermi level changes and the energy gap decreases. It has been established that, not only for pure systems but including those doped with Y₂O₃, the main contribution to the formation of the conduction band is made by the p-states of electrons. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of -1.22 eV, as well as by the method of molecular chemisorption with an energy of -0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of -1.84 eV. Dissociative adsorption of water occurs at an energy of -1.23 eV, near the yttrium atom. The calculations showed that ab initio research methods are capable of describing the mechanism of phase transitions of materials under the influence of alloying. That is, by optimizing the parameters of DFT calculations, it is possible to observe the effects of doping on other physical and chemical properties of materials, which are still beyond the scope of quantum chemical modeling. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation and can be used in designing humidity-to-electricity converters and creating solid oxide fuel cells based on ZrO₂.

Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts grown in suspension change from the elongated and flattened morphology observed under standard adherent culture conditions generating rounded cells with large nuclei and scant cytoplasm expressing the mesenchymal stem cell (MSC) marker (Sca1; Ly6A) within 24hrs. Based on this initial observation, we describe here a suspension culture method that, irrespective of the lineage used, mouse fibroblast, primary human somatic cells (fibroblasts, hepatocytes and keratinocytes), is capable of generating a high yield of cells in spheroid form which display expression of ASCs surface markers, circumventing the anoikis which often occurs at this stage. Moreover, mouse fibroblasts-derived spheroids can be differentiated into adipogenic and osteogenic lineages. Analysis of single cell RNA sequence data identified 8 distinct cell clusters with one in particular comprising approximately 10% of the cells showing high levels of proliferative capacity expressing high levels of genes related to MSCs and self-renewal as well as extracellular matrix (ECM). We believe the rapid, high-yield generation of proliferative, multi-potent ASC-like cells by the process we term suspension-induced stem cell transition (SIST) could have significant implications for regenerative medicine.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Background: no reports have examined the profile of drug-induced dysphagia in detail. The goal of this study was to investigate if there are any differences in the profiles of drug-induced dysphagia. Methods: This study used the Japanese Adverse Drug Event Report (JADER) database. Further, reported odds ratios (RORs) were used to analyze data on adverse drug events from 2004 to 2021. The top ten drugs with the most drug-induced dysphagia occurrences were used as target drugs. The association between RORs and drug-induced dysphagia caused by the target drugs was evaluated, and the age distribution and time of onset of drug-induced dysphagia for each drug were compared. RORs were the primary endpoint. Moreover, age and time of onset of drug-induced dysphagia were secondary outcomes. Results: In total, 756,965 reports were analyzed. All the target drugs were associated with drug-induced dysphagia. Among them, cevimeline was a novel finding, as no dysphagia was observed during the clinical trial. For most drugs, the onset of drug-induced dysphagia was occurring within approximately 25 days of administration. However, even after long-term use, paroxetine and milnacipran were associated with drug-induced dysphagia. Conclusion: The onset profile of drug-induced dysphagia may differ from one drug to the next.

Perilla frutescens leaves are expected to exhibit antioxidant activity and amyloid-β (Aβ) aggregation inhibitory activity due to the presence of polyphenol-type compounds, etc. These activities fluctuate daily; however, measuring the contents of constituents and functionalities is cumbersome and unsuitable for instantaneous measurements in the field. In this study, we developed a facile method to analyze the activity and content of the components in leaves on-site based on the fluorescence spectra obtained by irradiating the perilla leaves with excitation light. The constituent contents (Chlorophyl (Chl), Total polyphenol content (TPC), Total flavonoid content (TFC), rosmarinic acid (RA) and functional properties DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), Aβ aggregation inhibitory activity) were evaluated using established analytical techniques. The correlation between the fluorescence spectrum and the contents and activities was calculated using normalized difference spectral index (NDSI), ratio spectral index (RSI), and difference spectral index (DSI) analyses. We identified a predictive model with a high coefficient of determination R² ≥ 0.57 for content of the constituents, and R² ≥ 0.49 for functional properties. This allows convenient, simultaneous, and non-destructive monitoring of the constituent contents and the functionalities of perilla leave and a simple harvest-time diagnosis. The model established using this method is simple and suggesting that it can simultaneously infer the constituents and functionalities of perilla leaves.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

In this study, we considered the structural stability, electronic properties, and phonon dispersion of the cubic (c-ZrO₂), tetragonal (t-ZrO₂), and monoclinic (m-ZrO₂) phases of ZrO₂. We found that the monoclinic phase of zirconium dioxide is the most stable among the three phases in terms of total energy, lowest enthalpy, highest entropy, and other thermodynamic properties. The smallest negative modes were found for m-ZrO₂. Our analysis of the electronic properties showed that during the m–t phase transformation of ZrO₂, the Fermi level first shifts by 0.125 eV toward higher energies and then decreases by 0.08 eV in the t–c cross-section. The band gaps for c-ZrO₂, t-ZrO₂, and m-ZrO₂ are 5.140 eV, 5.898 eV, and 5.288 eV, respectively. Calculations based on the analysis of the influence of doping 3.23, 6.67, 10.35, and 16.15 mol. %Y₂O₃ onto the m-ZrO₂ structure showed that the enthalpy of m-YSZ decreases linearly, which accompanies further stabilization of monoclinic ZrO₂ and an increase in its defectiveness. In this case, the position of the Fermi level changes abruptly, and the energy gap decreases. It has been established that, not only for pure systems but including those doped with Y₂O₃, the main contribution to the formation of the conduction band is made by the p-states of electrons. The t-ZrO₂ (101) and t-YSZ (101) surface models were selected as optimal surfaces for water adsorption based on a comparison of their surface energies. An analysis of the mechanism of water adsorption on the surface of t-ZrO₂ (101) and t-YSZ (101) showed that H₂O on unstabilized t-ZrO₂ (101) is adsorbed dissociatively with an energy of -1.22 eV, as well as by the method of molecular chemisorption with an energy of - 0.69 eV and the formation of a hydrogen bond with a bond length of 1.01 Å. In the case of t-YSZ (101), water is molecularly adsorbed onto the surface with an energy of -1.84 eV. Dissociative adsorption of water occurs at an energy of -1.23 eV, near the yttrium atom. The obtained results complement the database of research works carried out in the field of the application of biocompatible zirconium dioxide crystals and ceramics in green energy generation and can be used in designing humidity-to-electricity converters and creating solid oxide fuel cells based on ZrO₂.

Laser-induced periodic surface structures (LIPSS) have gained significant attention due to their ability to modify the surface morphology of materials at the micro-nanoscale and show great promise for surface functionalization application. In this study, we specifically investigate the formation of LIPSS in silicon substrates and explore their impact on Surface-Enhanced Raman Spectroscopy (SERS) applications. This study reveals a stepwise progression of LIPSS formation in silicon, involving three distinct stages of LIPSS: 1) integrated Low-Spatial-Frequency LIPSS (LSFL) and High-Spatial-Frequency LIPSS (HSFL), 2) principally LSFL and 3) LSFL at the edge of the irradiated spot, elucidating the complex interplay between laser fluence, pulse number, and resulting surface morphology. Furthermore, from an application standpoint, these high-quality multi-scale periodic patterns lead to the next step of texturing the entire silicon surface with homogeneous LIPSS for SERS application. The potential of LIPSS-fabricated silicon substrates for enhancing SERS performance is investigated using thiophenol as a test molecule. The results indicate that the Au-coated combination of LSFL and HSFL substrate showcased the highest enhancement factor (EF) of 1.38 × 10^6. This pronounced enhancement is attributed to the synergistic effects of Localized Surface Plasmon Resonance (LSPR) and Surface Plasmon Polaritons (SPPs), intricately linked to HSFL and LSFL characteristics. These findings contribute to understanding LIPSS formation in silicon and their applications in surface functionalization and SERS, paving the way for sensing platforms.

A new layout optimization method for offshore wind farms is proposed to minimize power deficits due to wake effect. The main engine of the algorithm is a gradient-descent method, in which an analogy is established between power deficit and repulsive electrostatic potential energy. To achieve a maximum dispersion in the initial solution, throughout the optimization process, new turbines are included in the centre of the concession area, and quickly expand outward looking for areas with less potential, in turn pushing the previous ones. When the optimization process ends, to avoid local maximums, it enters into a process of suppression of the set of locations that cause the greatest potential (power deficit). Then, a potential map of the entire area is created and a greedy algorithm includes new turbines to complete the layout with the final number of turbines. To speed up the search process and the creation of the potential map, two simplifications have been validated and added: the spatial distribution of velocities has been converted into its equivalent with point symmetry; and, for turbines affected by multiple wakes, the power deficit has been calculated by using a linear aggregation of powers, instead of the usual linear (or quadratic) aggregation of speeds. Owing to this type of aggregation, the process is accelerated in a factor of 90.

In the absence of a holistic view of Landscape Sustainability, credible data and consistent information are needed to help decision making and support adaptive management. However, consolidated tools (system of standards and controls) of assessment exist, but show a complexity of the references on one hand, and are mostly qualitative and environmental indicators based on the other hand. This review article deals with the theme of both environmental and landscape indicators in general, the principles and the fundamental definitions. The main models used, the prerequisites and various fields of application are also taken into consideration. Last but not least, various environmental and landscape indicators are presented and compared.

Landsat and Sentinel-2 data archives provide ever-increasing amounts of satellite data for studying land cover and land use change (LCLUC) over the past four decades. However, the availability of cloud-, shadow-, and snow-free observations varies spatially and temporally due to climate and satellite data acquisition schemes. Spatio-temporal heterogeneity poses a major issue for some time-series analysis approaches, but can be addressed with pixel-based compositing that generates temporally equidistant cloud-free or near-cloud free synthetic images. Although much consideration is given to methods identifying the ‘best’ pixel value for each composite, determining the aggregation period receives less attention and is often done arbitrary, or based on expert intuition. Here, we evaluated data compositing windows ranging from five days to one year for 1984-2021 Landsat and 2015-2021 Sentinel‑2 time series across Europe. We considered separate and joint use of both data archives and analyzed spatio-temporal availability of composites during each calendar year and pixel-specific growing season. We reported mean annual composites’ availability investigating differences among biogeographical regions, checked feasibility of pan‑European analyses for three LCLUC applications based on annual, monthly and 10-day composites, and analyzed the shortest feasible compositing window ensuring ≥50% temporal data availability and interpolation of the remaining composites for individual years and across a variety of medium- and long‑term time windows. Our results highlighted low data coverage in the 1980s, 1990s, and in 2012, as well as spatial variability in data availability driven by climate and orbit overlaps, which altogether impact spatio-temporal consistency of medium- and long-term time series, limiting feasibility of some LCLUC analyses. We demonstrated that prior to 2011 monthly composites ensured overall 50-62% data coverage for each calendar year, and ~75% afterwards, with further increase to ~82% when Landsat and Sentinel-2 were combined. Temporal consistency of monthly composites was overall low and temporal interpolation augmenting up to 50% missing data each year and across a time window of interest, ensured feasibility of analyses. Applications based on shorter than monthly composites were challenging without joining Landsat and Sentinel‑2 archives after 2015, and beyond the Mediterranean biogeographical region. Using pixel-specific growing season data typically boosted data availability in most geographies and diminished most of the latitudinal differences, but feasibility of complete time series with sub-monthly compositing windows was still restricted to the most recent years, and required data interpolation. Overall, our analyses provided a detailed assessment of Landsat and Sentinel-2 data availability over Europe, and based on selected application examples, highlighted often lacking spatio-temporal consistency of time series with sub-monthly compositing windows and long-time periods, which might hinder feasibility of some LCLUC applications.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

Hepatitis B virus (HBV) remains a dominant cause of hepatocellular carcinoma (HCC). Recently it was shown that HBV and woodchuck hepatitis virus (WHV) integrate into hepatocyte genome minutes after invasion. Retrotransposons and transposable sequences were frequent sites of the initial insertions suggesting a mechanism for spontaneous HBV DNA disperse throughout hepatocyte genome. Several somatic genes were also identified as early insertional targets in infected hepatocytes and woodchuck livers. Head-to-tail joints (HTJs) dominated amongst fusions indicating their creation by non-homologous-end-joining (NHEJ). Their formation coincided with robust oxidative damage of hepatocyte DNA. This was associated with activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated dsDNA repair as reflected by augmented transcription of PARP1 and XRCC1, the PARP1 binding partner, OGG1, a responder to oxidative DNA damage, and by increased activity of NAD+, a marker of PARP1 activation, and HO1, an indicator of cell oxidative stress. The engagement of the PARP1-mediated NHEJ repair pathway explains HTJ format of the initial merges. The findings showed that HBV and WHV are immediate inducers of oxidative DNA damage, hijack dsDNA repair to integrate into hepatocyte genome and by this may initiate pro-oncogenic process. Tracking initial integrations may uncover early markers of HCC and help to explain HBV-associated oncogenesis.

Oxidative stress-mediated damage is often a downstream result of Parkinson’s disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2, and 4. Utilizing N27 rat dopaminergic cells and C57Bl/6 mice, we confirmed that the exposures of alpha-synuclein preformed fibrils (PFF) induced protein aggregation, a hallmark in PD pathology. In vitro assessment of the novel compound revealed an increase in cell viability and decreases in cytotoxicity, ROS, and protein aggregation (Thioflavin-T stain) against PFF exposure at the optimal concentration of 10nM. Concomitantly, the oral treatment alleviated motor deficits in behavioral tests, such as hindlimb clasping, rotarod, pole, nesting, and grooming test, via reducing protein aggregation, based on rescued dopaminergic neuronal loss. The suppression of NOX-1, 2, and 4 within the striatum and ventral midbrain regions including SNc contributed to neuroprotective/recovery effects, making it a potential therapeutic option for PD.

Most of the current methods for stabilizing electric arc furnace (EAF) slag are time-consuming and cannot be completely stabilized. In view of this, this study aimed to apply microbial‑induced calcium carbonate precipitation (MICP) technology in the stabilization of EAF reducing slag, and this was to be achieved by using the reaction between carbonate ions and free calcium oxide (f-CaO) in reducing slag to form a more stable calcium carbonate to achieve the purpose of stabilization. The test results showed that, when the EAF reducing slag aggregates (ERSAs) were immersed in Bacillus pasteurii bacteria solution or water, the f-CaO contained in it would react such that stabilization was achieved. The titration test results showed that the f-CaO content of the ERSAs immersed in the bacterial solution and water decreased. The expansion test results of the ERSAs that were subjected to hydration showed that the seven-day expansion of ERSAs after biomineralization could meet the Taiwan regulation requirement of a less than 0.5% expansion rate. The thermogravimetric analysis showed that both the experimental group and the control group might contain calcium carbonate compounds. The results of the X-ray diffraction analysis showed that the CaCO3 content in the ERSAs that were immersed in the bacterial solution was significantly higher than those that were immersed in water. Moreover, the compressive strength test results of concrete prepared with ERSAs showed that the compressive strength of the control group concrete began to decline after 28 days. In contrast, the experimental group concrete had a good stabilization effect, and there was no decline in compressive strength until the age of 180 days. At the age of 240 days, the surface cracks of the experimental group were particularly small, while the surface of the control group showed obvious cracks. These results confirmed that a mineralization reaction with B. pasteurii bacteria could be used as a stabilization technology for ERSAs.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

The time-resolved CIDNP method can provide information about degenerate exchange reactions (DEE) involving short-lived radicals. In the temperature range from 8 to 65°C, the DEE reactions of the guanosine-5’-monophosphate anion GMP(-H)- with the neutral radical GMP(-H)•, of the N-acetyl tyrosine anion NacTyrO- with a neutral radical NacTyrO• and of the tyrosine anion TyrO- with a neutral radical TyrO• were studied. In all the studied cases, the radicals were formed in the reaction of quenching triplet 2,2’-dipyridyl. The reorganization energies were obtained from Arrhenius plots. The rate constant of the reductive electron-transfer reaction in pair GMP(-H)•/TyrO- was determined at T = 25°C. Rate constants of GMP(-H)• radical reduction reactions with TyrO- and NacTyrO- anions calculated by the Marcus cross relation differ from the experimental ones by two orders of magnitude. The rate constants of several other electron transfer reactions involving GMP(-H)-/•, NacTyrO-/•, and TyrO-/• pairs calculated by cross relation agree well with the experimental values. The rate of nuclear paramagnetic relaxation was found for the 3,5 and β-protons TyrO• and NacTyrO•, the 8-proton GMP(-H)• the 3,4-protons DPH• at each temperature. In all cases, the dependences of the rate of nuclear paramagnetic relaxation on temperature are described by the Arrhenius dependence.

Transit-oriented development (TOD), such as metro depot and over-track building complexes, has expanded rapidly in China. Over-track building construction has the advantage of comprehensive utilization of land resources, ease of commuting to work, and provide funds for subway construction. However, there still has a pending problem, disturbance of railway vibration, for TOD. Excessive noise and vibration seriously affect people’s life. To address this challenge, field measurements are used to obtain the vibration source characteristics and vibration propagation of the ground and the superstructure in this study. And the typical metro depot with over-track building in Wuhan was selected. The effects of vibration on the surrounding ground and adjacent buildings caused by the operation of trains have been measured, and the propagation law of train-induced ground vibration acceleration in the time and frequency domains has been analyzed. The distribution and propagation laws of vibration noise, structural noise and secondary structure noise in sensitive areas such as the throat area, depot area, test section and access section of the over-track buildings and their impact laws on the over-track buildings are obtained. And the effectiveness of the vibration and noise reduction methods used were evaluated. Results show that within 43 m from the train running track, the train running induced vertical vibration acceleration level in the high-rise building peak size of 58.8 dB, the average value of 55.62 dB; vibration frequency components are mainly 40-60 Hz. The findings might provide useful insight for designing vibration mitigation systems in new metro depots with over-track buildings.

Fluorophores with a tetraphenylethylene (TPE) core are attracting increasing interest because of their aggregation-induced emission (AIE) behaviour, which makes them particularly suitable when dispersed in thin-layer films. We propose the synthesis and use of a novel TPE fluorophore (hereafter called TPE-BPAN) decorated with two dimethylamino push groups and a 4-biphenylacetonitrile pull moiety. In tetrahydrofuran solutions, TPE-BPAN showed a broad absorption spectrum, and an intense emission is observed when a non-solvent as water is added in amounts of 70% and above. We selected and synthetized five different polymer matrices for TPE-BPAN with decreasing polarity: a) poly(methylmetacrylate) homopolymer (PMMA); b), c), and d) three copolymers of methyl methacrylate and cyclohexyl methacrylate at different compositions (P(MMA-co-CHMA) 75:25, 50:50, 25:75 mol%); e) poly(cyclohexyl methacrylate) homopolymer (PCHMA). The presence of a less polar comonomer as cyclohexyl methacrylate appeared to enhance the emission behaviour of TPE-BPAN, which displayed the highest quantum yield (QY) in P(MMA-co-CHMA) 75:25 in all the range of concentration studied from 0.4 wt.% to 2.0 wt.%. Further reduction in polarity lowered QY to the values of PMMA films; also, lower adhesion to the glass and a marked fragility of the films were observed. Referring to the P(MMA-co-CHMA) 75:25 films, QY values decreased from over 40% at 0.4 wt.% to about 30% at 2.0 wt.%, which is still helpful for energy harvesting applications such as luminescent solar concentrators (LSC). LSC performances were not significantly affected by the matrix's lower polarity and resulted in around one-third of the state-of-the-art due to the lower QY of TPE-BPAN. The theoretical investigation on density functional theory (DFT) clarified the origin of the observed AIE and the role played by the environment in modulating the photophysical behaviour.

The theory of electron spin has been proposed for a century, but the study of quantum effects in biological molecules is still in its infancy. Chirality-induced spin selectivity (CISS) is a very modern theory that can explain many biochemical phenomena. In this paper, we propose a new theoretical model based on CISS theory and quantum chemistry theory, which can well explain the theoretical explanation of the chiral selectivity of chiral proteins. Moreover, this theory can predict the spin state of corresponding chiral molecules. Taking L-DOPA and AADC enzyme as examples, this theoretical model solves the theoretical explanation of AADC enzyme's chiral catalysis selectivity problem and successfully predicts the spin state of L-DOPA and D-DOPA's valence electrons.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional Indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. Based on our observations, we conclude that 4LG with WIIC is a promising TCE for flexible smart windows.

When developing bone implants Young's modulus is one of the primary characteristics of the material that should be considered. The study focuses on the possibility of regulating the modulus of the alloy Ti-50.8 at % Ni by varying its initial structure as well as aging-induced microstructure in a wide range. Microstructure observations were performed using TEM and SEM observations. The calorimetric studies of martensitic transformations were carried out using "Mettler Toledo 822e". Tensile tests were performed in a test temperature range of ‒196≤T≤+100°C using an «IN-STRON 5966». The grain/subgrain size of B2-austenite strongly affects the modulus magnitude. This effect is ambiguous for a material with a grain size of 0.13–3 µm and depends on the test temperature. The effectiveness of aging on the modulus reduction depends on the initial structure: it is most pronounced in an alloy with a relatively coarse grain size of 9 µm and brings a decrease by 3.8 times at a temperature of 37°C. Bone-like elastic modulus (10–30 GPa) at a human body temperature of 37°C is realized in an aged fine-grained NiTi alloy. An ultrafine-grained sub-structure exhibits he same values of Young's modulus in the temperature range from -100°С to 25°С.

The microstructure of oil pipeline steels is polycrystalline due to the presence of a complex grain boundary (GB) network in them. The performance of them when exposed to stresses in corrosive environments is largely dictated by the interplay between the hydrogen (H) diffusion, the dislocation slip, and their interactions with the GBs. However, the slip-GB interaction in the presence of H and the subsequent cracking along the GBs remains not fully understood up to date. It is challenging to simultaneously resolve the collective dislocation motions away from the GBs together with the H diffusion near the atomically structured GBs using single-scale techniques. To address this challenge, taking bcc iron as a model material, here we present a a concurrent atomistic-continuum (CAC) computational analysis of the interaction between dislocation slip and a H-charged GB. With the large number of dislocations-mediated plastic flow away from the GB together with the atomistic structure evolution at the GB being simultaneously retained, several main findings from our simulations are: (i) the large number of dislocation-mediated pileup-induced internal stress nearby the H-charged GB can be as high as 3GPa; (ii) the more dislocations accumulated nearby the GB, the slower H diffusion ahead of the slip-GB intersection; (iii) H atoms diffuse fast behind the pileup tip, get trapped within the GB, and diffuse slow ahead of the pileup tip; (iv) the local stresses nearby the pileup tip exhibits a strong heterogeneity along the dislocation line direction. This differs from the common wisdom in many existing 2D theories/models. The buildup of such a high local stress heterogeneity leads to inhomogeneous H diffusion within the GB plane. The CAC simulation-predicted local H diffusivity, Dpileup−tip, and local stresses, σ, nearby the GB are then correlated with each other and consolidated into a mechanics model by considering the dislocation pileup as an Eshelby inclusion. These findings will provide researchers with opportunities to: (a) characterize the coupled dynamics between plasticity, H diffusion, and crack initiation underlying the hydrogen-induced cracking (HIC); (b) develop mechanism-based constitutive rules to be used in diffusion-plasticity coupling models for understanding the interplay between mechanical and mass transport in materials at the continuum level; and (c) connect the atomistic deformation physics of polycrystalline materials with their overall performance in aqueous environments, which is currently difficult to achieve in laboratory experiments.

Proliferating cell nuclear antigen (PCNA) is the key regulator of human DNA metabolism. One important interaction partner is p15, involved in DNA replication and repair. Targeting the PCNA-p15 interaction is a promising therapeutic strategy against cancer. Here, a Förster resonance energy transfer (FRET)-based assay for the analysis of PCNA-p15 interaction was developed. Next to the application as screening tool for the identification and characterization of PCNA-p15 interaction inhibitors, the assay is also suitable for the investigation of mutation-induced changes in their affinity. This is particularly useful for analysing disease associated PCNA or p15 variants at the molecular level. Recently, the PCNA variant C148S has been associated with Ataxia-telangiectasia-like disorder type 2 (ATLD2). ATLD2 is a neurodegenerative disease based on defects in DNA repair due to an impaired PCNA. Incubation time dependent FRET measurements indicated no effect on PCNAC148S-p15 affinity, but on PCNA stability. The impaired stability and increased aggregation behaviour of PCNAC148S was confirmed by intrinsic tryptophan fluorescence, DSF and AF4 measurements. The analysis of the disease associated PCNA variant demonstrated the versatility of the interaction assay as developed.

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give an information on biophysical properties of blood sample under continuous ESR. In this study, three physical properties, including, τ₀, ESR_τ, and AI_I, are suggested to quantify mechanical variations of blood under continuous ESR. To demonstrate the proposed method, blood sample is loaded into a driving syringe. The blood flow rate is set in a periodic on–off pattern. Blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of blood stream in the coflowing channel. Both τ₀ and ESR_τ are then obtained by analyzing the blood shear stress. Simultaneously, the AI_I is evaluated by analyzing the image intensity of blood flow. According to the experimental results, the τ₀ exhibits consistent trends with respect to hematocrit as well as diluent. The ESR_τ and AI_I showed a reciprocal relationship each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentration of dextran solution and fibrinogen). In conclusion, the present method can detect variations of blood sample under continuous ESR effectively.

Volumetric modification of transparent materials by femtosecond laser pulses is successfully used in a wide range of practical applications. The level of modification is determined by the locally absorbed energy density, which depends on numerous factors. In this work, it is shown experimentally and theoretically that, in a certain range of laser pulse energies, the peak of absorption of laser radiation for doughnut-shaped (DS) pulses is several times higher than for Gaussian ones. This makes the DS pulses very attractive for material modification and direct laser writing applications. Details of the interaction of laser pulses of Gaussian and doughnut shapes with fused silica obtained by numerical simulations are presented for different pulse energies and compared with the experimentally obtained data. The effect of absorbed energy delocalization with increasing laser pulse energy is demonstrated for both beam shapes while, at relatively low pulse energies, the DS beam geometry provides a stronger local absorption compared to Gaussian one. Implications of a DS pulse action on post-irradiation material evolution are discussed based on thermoelastoplastic modeling.

Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the (1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan or mitomycin C. In contrast, combination of TRAIL and oxaliplatin, irinotecan or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC.

Land use/land cover (LULC) changes have a substantial influence on ecosystem services. The objective of this study is to estimate LULC dynamics induced ecosystem service values (ESV) changes in Western Ethiopia. Data were acquired from Landsat images of the area for four periods (1990-2020), and 221 sample households. The areas of LULC classes and the improved ESV coefficients of Costanza et al (1997) were used estimate ESV changes in 1990-2020. Forest provides diverse provisions, regulatory, supportive and cultural services. Analysis of the Landsat images showed that forest, farmland, settlement, water body and bare-land were the major LULC classes in the study area. While forest ESV had accounted 46.1% (US$ 4.95 million) of the ESV of Wayu-Tuka district in 1990, farmland ESV constituted the largest share (63.3%, US$ 5.21 million) of the ESV of the area after 30 years (2020). The ESV of forest and bare-land showed decreasing trends in three decades (1990-2020) but the farmland service value revealed an increasing trend in the same periods. Forest ecosystem exhibited the largest service value loss (US$ 3.91 million) in 1990-2020; whereas, the service value gain of farmland was only US$ 2.2 million although farmland was responsible for the conversion of the largest area size (9,766.5 ha) from other land covers in 30 years. LULC change induced net ESV loss of the district in three decades (1990-2020) was 23.4% (US$ 2.51 million). Land conversion due to expansion of farmland (by 9,766.5 ha) and settlement (by 4,061.3 ha) was the main cause for the LULC dynamics and the significant ESV loss in 1990-2020. Thus, the government and local people should cooperate so as to curb the steady degradation of forest and its ecosystem services in Wayu-Tuka district, Western Ethiopia.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day preexposure to one toxin at LC5 followed by 6-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50, were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

Laser additively manufactured (LAM) Ti–6Al–4V alloy has huge application potential in aerospace structural parts such as turbine blades. However, there are few studies on the fatigue properties of such LAM parts under vibration loading, particularly with regard to anisotropy. In this paper, vibration fatigue properties of LAM Ti-6Al-4V by laser melted deposition process were investigated along the transversely deposited (TD) direction and parallelly deposited (PD) direction. Through the first-order bending vibration experiments, LAM Ti-6Al-4V alloy exhibits obvious anisotropic fatigue properties and significant dispersion in fracture position. The fracture morphology analysis reveals that the vibration fatigue failure was mainly dominated by the LAM process-induced defects and the microstructure. For the LAM samples without defects at crack initiation sites, the fatigue behavior is controlled by the prior β columnar grains with preferential orientation, which leads to enhanced fatigue crack propagation resistance for the PD samples. For the LAM samples with defects at initiation sites, having lower fatigue lives, the fatigue anisotropy strongly depends on the projection area of the lack-of-fusion defects relative to the loading direction, resulting in better fatigue performance for the TD samples.

A switchable and tunable terahertz (THz) metamaterial based on photosensitive silicon and Vanadium dioxide (VO2) was proposed. By using finite-difference time-domain (FDTD) method, the transmission and reflective properties of the metamaterial were investigated theoretically. The results imply that, the metamaterial can realize a dual electromagnetically induced transparency (EIT) or two narrow-band absorption depending on the temperature of the VO2. Additionally, the magnitude of the EIT and two narrow-band absorption can be tuned by varying the conductivity of photosensitive silicon (PSi) via pumping light. Correspondingly, the slow light effect accompanying the EIT can also be adjusted.

When there are multiple key strata in the overburden of deep coal seam and the surface subsid-ence coefficient after mining is small, it indicates that the overlying key strata fail to break com-pletely after mining. On this occasion, the stress concentration on the working face occurs easily, which in turn leads to the occurrence of dynamic disasters such as rock burst. This study adopted a comprehensive analysis method of field monitoring and numerical simulation to explore the in-fluence of key stratum on the evolution law of mining-induced stress in the working face. Dis-tributed optical fiber sensor (DOFS) and surface subsidence GNSS monitoring system were re-spectively arranged inside and at the mouth of the ground observation borehole. According to the monitoring results of strain obtained from DOFS, the height of broken stratum inside the overlying strata was obtained; according to the monitoring results of surface subsidence, the sur-face subsidence coefficient was proved to be less than 0.1, indicating that the high key stratum does not break completely, but enters a state of bending subsidence instead. In order to reveal the influence of key stratum on the mining-induced stress of working face, two 3DEC numerical models with and without key stratum were established for comparative analysis. As the numeri-cal simulation results show, when there are multiple key strata in the overburden, the stress in-fluence range and stress concentration coefficient of coal seam after mining are relatively large. The study revealed the working mechanism of rock burst accidents after large-scale mining and predicted the potential area of rock burst risk after the mining of the working face, which has been verified by field investigation. The research results are of great guiding significance for the revelation of the working mechanism of rock burst in deep mining condition and its prevention and control.

Neuronal cell fate is predominantly controlled by the effects of growth factors, such as neurotrophins, and the activation of a variety of signaling pathways acting through neurotrophin receptors, namely Trk and p75 (p75NTR). Despite their beneficial effects on brain function, their therapeutic use is compromised, due to their polypeptidic nature and blood–brain-barrier impermeability. To overcome these limitations, our previous studies have proven that DHEA-derived synthetic analogs can act like neurotrophins, lacking endocrine side effects. The present study focuses on the biological characterization of a newly synthesized analog, ENT-A044, and its role on inducing cell specific functions of p75NTR. We show that ENT-A044 can induce cell death and phosphorylation of JNK protein by activating p75NTR. Additionally, ENT-A044 can induce the phosphorylation of TrkB receptor, indicating that our molecule can activate both neurotrophin receptors, leading towards the protection of neuronal populations that express both receptors. Furthermore, the present study demonstrates for the first time the expression of p75NTR in human induced Pluripotent Stem Cells - derived Neural Progenitor Cells (hiPSCs - derived NPCs) and receptor-dependent cell death induced by ENT-A044 treatment. In conclusion, ENT-A044 could be proven a lead molecule for the development of novel pharmacological agents, aiming on new therapeutic approaches and research tools, by controlling p75NTR actions.

Lichens are unique extremophilic organisms due to their phenomenal resistance to adverse environmental factors, including ultraviolet (UV) irradiation. Melanization plays a special role in the protection of lichens from UV-B stress. In present study, we analyzed the binding of melanins with the components of cell walls of mycobiont of upper cortex in the melanized lichen thalli Lobaria pulmonaria. Using scanning electron and atomic force microscopy, the morphological and nanomechanical characteristics of melanized layer of mycobiont cells were visualized. Melanization of lichen thalli led to the smoothing the surface relief and thickening mycobiont cell walls and resulted in the increase of deformation values and reduction of adhesion properties of lichen thallus. Treatment of thalli with hydrolytic enzymes, especially chitinase and lichenase, enhanced the yield of melanin from melanized thalli and release of carbohydrates, while treatment with pectinase increased the release of carbohydrates and phenols. Our results suggest that melanin by firmly binding with hyphal cell wall carbohydrates, particularly chitin and 1,4-β-glucans, can form associations, strengthen the melanized upper cortex of lichen thalli, and thereby can contribute to lichen survival under UV stress.

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

This study presents a novel approach to analyzing the present value of total profit for non-participating and participating insurance policies in order to determine the optimal profitability of non-participating and participating insurance policies based on applying the approach used in operations research to the field of finance. As such, a comprehensive insurance product evaluation model was developed using both mathematical models and numerical analysis to evaluate the demand for non-participating and participating life insurance policies in response to changes in interest rates. The findings indicate that non-participating life insurance policies offer greater solvency for insurance companies compared to participating policies. The study also highlights the significance of spontaneous and induced demand in determining the total profit of both types of policies. The study concludes that life insurance companies should focus on generating spontaneous consumer demand, reducing induced demand, and implementing the optimal pricing strategy to achieve maximum profits.

Glycerol has found its applications as a heat-transfer fluid in heat exchangers, and as a compo-nent of functional solutions in biosensor analysis. Flowing non-aqueous fluids are known to be able to induce electromagnetic fields due to triboelectric effect. These triboelectrically generated electromagnetic fields can affect biological macromolecules. Horseradish peroxidase (HRP) is widely employed as a convenient model object for studying how external electric, magnetic, and electromagnetic fields affect enzymes. Herein, we have studied whether the flow of glycerol in a ground-shielded cylindrical coil affects the HRP enzyme incubated at a 2 cm distance near the coil’s side. Atomic force microscopy (AFM) has been employed in order to study the effect of glycerol flow on HRP at the nanoscale. Increased aggregation of HRP on mica has been observed after the incubation of the enzyme near the coil. Moreover, the enzymatic activity of HRP has also been affected. The results reported can find their application in biotechnology, food technology and life sciences application, considering the development of triboelectric generators, en-zyme-based biosensors and bioreactors with surface-immobilized enzymes. Our data can also be of interest for scientists studying triboelectric phenomena.

Background: Pteropodine (PT) is a component of some plants with potentially useful pharmaco-logical activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the an-ti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. Methods: To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect was evaluated by determining the myeloperoxidase enzyme activity. Results: PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 52 to 74% of inhibitory effect of PT in the rat paw edema test, 52% of reduction of the pleural exudate volume, and low neutrophil count (28%), when compared to the control group. We also found a 81% of inflammatory inhibition of the ear edema, and a significant myeloperoxidase enzyme inhibition by the three doses of PT. Conclusions: PT exerted a potent an-ti-inflammatory effect in the acute inflammation model in rodents.

Harbor porpoise are typically seen in small groups of 1-3 individuals, with aggregations of 20+ individuals treated as rare events. Since the 1990s, the harbor porpoise population in the Salish Sea has seen a significant recovery, which has led to an increased number of observed aggregations that exceed the more usual small group sizes. By combining the observational data of United States and Canadian research organizations, community scientists, and whale watch captains or naturalists, we demonstrate that harbor porpoise aggregations appear to be more common than previously known, with 160 aggregations documented in 2022 alone. Behavioral data also indicated that foraging behaviors were common and social behaviors, like mating, were seen more often during these encounters compared to small groups. Other behaviors that are considered to be rare or unknown, were also observed during these encounters, including cooperative foraging and vessel approach. These aggregations are likely important foraging and social gatherings for harbor porpoises. This holistic approach integrating data from two countries and multiple sources provides an ecosystem level assessment that more effectively reflects the habitat use of harbor porpoise in this region that do not recognize the socio-political boundaries imposed upon the natural world.

This paper deals with the quantitative analysis of measured fracture-induced electromagnetic radiation (FEMR) in the vicinity of the Dead Sea Transform using the Angel-M1 instrument, which enables the recording of FEMR signals in a 3D manner. Results show both the possibility of estimating the sizes of micro-fractures that are the sources of the radiation, and of assessing the direction of their location to the measuring device and the range of magnitude Mw of the impending "events" (EQ's) associated with the present FEMR measurements. Moreover, the relation between the measured FEMR activity (the number of FEMR hits per unit time) and the FEMR event magnitudes shows consistency with the Gutenberg-Richter relationship for the region. Such measurements could therefore constitute a preliminary 'field reinforcement' towards an EMR valid method for a real earthquake forecast, which would provide much earlier warnings than the seismic ones. Obviously, the present observed FEMR measurements can only be used as an assessment of the stress concentration and micro-fracturing in the region since they relate to the very initial nucleation phase of a "virtual" (extremely low Richter scale value) earthquake, but they do provide the necessary feasibility test for a prediction method since all lab-measured FEMR features were confirmed also in the field.

Background: Intermittent claudication is a frequent complaint in lower extremity artery disease, but approximately two thirds of patients are asymptomatic, mostly in diabetic population. Non-invasive angiological and microrheological tests among diabetic patients with and without intermittent claudication were studied. Methods: 98 diabetic patients were included and divided into two groups: 20 patients (63.5±8.8 yrs, 55% men, 45% women) had intermittent claudication, 78 patients (65.5±9.3 yrs, 61.5% men, 38.5% women) were asymptomatic. Hand-held Doppler, transcutaneous tissue partial oxygen pressure (tcpO2) measurement, tuning fork test and 6-minute walk test were performed and erythrocyte aggregation was investigated. Results: Ankle/brachial index (p<0.02), and tcpO2 measured during provocational tests (p<0.003), 6-minute walk test (p<0.0001) were significantly deteriorated in the symptomatic group. Higher erythrocyte aggregation index and faster aggregate formation could be observed among claudicant patients (p<0.02). In spite of the statistically better results of the asymptomatic group, 13% of these patients had severe limb ischemia based on the result of tcpO2 measurement. Conclusion: Claudication could be associated with worse hemodynamical and hemorheological status in diabetics; nevertheless, severe ischemia can develop even in asymptomatic subjects which can be revealed by noninvasive vascular tests, which highlights the importance of the early instrumental screening of the lower limbs.

Unmanned Aerial Vehicles (UAVs) image object detection has great application value in military and civilian fields. However, the objects in the captured images from UAVs have problems of large scale variation, complex backgrounds, and a large proportion of small objects. To resolve these problems, a multi-scale object detector based on coordinate and global information aggregation is proposed, named CGMDet. Firstly, a Coordinate and Global Information Aggregation Module (CGAM) is designed by aggregating local, coordinate, and global information, which can obtain features with richer context information. Secondly, a Multi-Feature Fusion Pyramid Network (MF-FPN) is proposed, which can better fuse features of different scales and obtain features containing more context information through repeated use of feature maps, to better detect multi-scale targets. Moreover, more location information of low-level feature maps is integrated to improve the detection results of small targets. Furthermore, we modified the bounding box regression loss of the model to make the model more accurately regress the bounding box and faster convergence. Finally, the proposed CGMDet was tested on VisDrone and UAVDT datasets and mAP0.5 of 50.9% and 48% was obtained, respectively. At the same time, our detector achieved the best results compared to other detectors.

Large-area nanostructuring of glasses using intense laser beam remains a difficult task due to the extreme non-linear absorption of the laser energy by the material. Precise optimization of the process parameters is essential for fabricating nanostructures with large area coverage. In this study, we report the findings on creating high spatial frequency LIPSS (HSFL) on borosilicate glass through direct laser writing, using a femtosecond laser with a wavelength λ = 800 nm, pulse duration τ = 35 fs, and repetition frequency frep = 1 kHz. The orientation of the HSFL was found to be parallel to the electric field vector. We measured the single pulse ablation threshold (Fth=3.87±0.26 J/cm2) and incubation factor (S=0.68±0.03) of Borosilicate glasses for precise control for large area surface structuring. Single-spot experiments indicate that uniform LIPSS formation is limited by melt formation inside the irradiated area for higher fluence and a larger number of irradiated laser pulses. The orientation of the scan axis with the laser beam polarization is found to be significantly influencing the uniformity of the large area processing. We found that the orientation of the scan axis with the laser beam polarization significantly affects the uniformity of large-area processing, with redeposition and melt formation being higher when the scan axis is perpendicular to the laser beam polarization. Large-area processing of the borosilicate glass surface is done by line-by-line scanning over the surface with a scan orientation parallel to the laser beam polarization. The optical characterization reveals that the transmittance and reflectance of the borosilicate glass decreased significantly after processing. Also, the wettability of the surface has been changed from hydrophilic to super hydrophilic after processing. These chemical contamination-free and uniformly distributed structures have potential applications in optics, microfluidics, photovoltaics, and biomaterials.

Human induced pluripotent stem cell (hiPSC)-derived neural cells have been used at the preclinical stage of drug development. As previously reported, hiPSC-derived neurons exhibit greater tolerance to excitotoxicity than that of primary cultures of rodent neurons; however, the underlying mechanisms remain unknown. We therefore investigated the functions of L-glutamate (L-Glu) transporters, the most important machinery used to maintain low extracellular L-Glu concentrations, in hiPSC-derived neural cells. We also clarified the contribution of each L-Glu transporter subtype. At 63 days in vitro (DIV), we detected neuronal circuit functions in hiPSC-derived neural cells by a microelectrode array system (MEA). Exposure to 100 μM L-Glu for 24 hrs did not affect the viability of these 63 DIV neural cells. Pharmacological inhibition of excitatory amino acid transporter 1 (EAAT1) and EAAT2 blocked almost 100% of L-Glu uptake. In this condition, L-Glu exposure dramatically decreased cell viability. These results suggest that in hiPSC-derived neural cells, EAAT1 and EAAT2 are predominant L-Glu transporters, and their uptake potentials are stronger than those of primary cultures of rodent neurons. Furthermore, hiPSC-derived neural cells may be useful for screening drugs that target L-Glu transporters.

Ground-based high-power lasers enable to, in principle, deorbit any kind of space debris object from the low Earth orbit (LEO) by remotely inducing laser-ablative momentum. However, the assessment of efficiency and operational safety depends on many factors like atmospheric constraints or the risk of debris disintegration during irradiation. We analyze laser momentum for a great variety of target geometries and sizes, and – for the first time in a large-scale simulation – include thermal constraints for laser irradiation configuration. Using a coherently coupled 100 kJ laser system at 1030 nm wavelength, 5 ns pulse duration in an optimized pointing elevation angle range, the pulse frequency should amount to less than 10 Hz to prevent fragment meltdown. For mechanically intact payloads or rocket bodies, repetition rates should be even lower. Small debris fragments sized between 10 and 40 cm can be de-orbited by around 100 to 400 station passes with head-on irradiation while objects exceeding 2 m typically require far more than 1000 irradiations for deorbit. Hence, laser-based debris removal cannot be considered a prime space sustainability measure tackling the top-risk large debris, yet it can provide for remediation of a multitude of small-sized debris using small networks of globally distributed laser sites.

The present paper describes a study case of the failure investigation of Duplex stainless steel (UNS S31803) on the tube and tube sheet section of a shell and tube heat exchanger BEM TEMA type with seawater as the cooling medium. Although UNS S31803 offers high strength, high resistance to chloride-induced SCC, and high resistance to pitting attack in chloride environments, in this study case, the heat exchanger experienced some material degradation; 26 tubes were leaked and plugged on both sides, and scales plugged 76 tubes. The examination in this study case revealed the formation of biofilm inside the tubes, XRD examination revealed that the film contained aragonite (CaCO3), and by using microstructural examination on the inner surface of the tube, the austenite grains were preferentially attacked by crevice corrosion. In this case, the failure was caused by crevice corrosion, and crevice corrosion was enhanced by microbiological-induced corrosion (MIC). Recommendations to avoid similar failures are also suggested in this paper.

Amyloids were conventionally referred to as extracellular and intracellular accumulation of Aβ42 peptide which causes the formation of plaques and neurofibrillary tangles inside the brain leading to the pathogenesis in Alzheimer’s disease. Subsequently, amyloid-like deposition was found in the etiology of Prion diseases, Parkinson disease, Type II Diabetes and Cancer which was attributed to the aggregation of Prion protein, α-Synuclein, Islet Amyloid Polypeptide Protein and p53 protein respectively. Hence, traditionally amyloids were considered as aggregates formed by the proteins or peptides exclusively. However, since the last decade it has been discovered that other metabolites like single amino acids, nucleobases, lipids, glucose derivatives etc. have propensity to form amyloid-like toxic assemblies. Several studies suggest direct implications of these metabolite assemblies in the patho-physiology of various Inborn errors of metabolisms like Phenylketonuria, Tyrosinemia, Cystinuria and Gaucher’s disease to name a few. In this review, we present a comprehensive literature overview which suggests amyloid-like structure formation as a common phenomenon for the disease progression and pathogenesis in multiple syndromes. The review on this topic is urgently required to create awareness about the understanding of fundamental molecular mechanism behind the origin of diseases from an amyloid perspective and possibly look for a common therapeutic strategy for the treatment of these maladies by designing generic amyloid inhibitors.

Given the pathological role of hyperphosphorylated Tau aggregation in Alzheimer’s disease (AD) our laboratory previously developed the novel Tau aggregation inhibitor peptide, RI-AG03. As Tau aggregates accumulate intracellularly, it is essential that Tau-targeting peptides efficiently traverse the cell membrane. In addition, these peptides need to avoid sequestration into cell organelles, particularly those involved in degradation, to ensure interaction with Tau in the cytoplasm. Here, we examine the cellular uptake and intracellular trafficking of RI-AG03 when the peptide is unconjugated or linked to nanoliposome carrier particles. The impact of adding the cell penetrating peptide (CPP) sequences, polyarginine (polyR) and transactivator of transcription (TAT), to RI-AG03 was also characterised. Our data show that the conjugation of CPP-containing RI-AG03 to liposomes dramatically increases cellular liposomes uptake. The majority of this uptake occurs via direct cell penetration. However, we find that macropinocytosis is also an important mechanism for unconjugated and RI-AG03-polyR-conjugated, but not RI-AG03-TAT-conjugated, liposome uptake. In agreement with this macropinocytosis-mediated internalisation, liposome lipids localise to lysosomes and macropinosomes following cellular uptake. However, while unconjugated RI-AG03 peptides also localise to lysosomes, liposome conjugation prevents this localisation, with the peptide detaching from the liposomes at the cell surface and evading organelle entrapment. Overall, this study demonstrates that CPP sequences and nanoliposomes carriers enhance the intracellular delivery of RI-AG03, furthering the possibility of the peptide’s use in targeting Tau pathology in AD.

In recent years, laser engraving has received widespread attention as a convenient, efficient, and programmable method, which has enabled the obtaining of high-quality porous graphene from various precursors. Laser engraving is often used to fabricate the dielectric layer with micro-structure for capacitive pressure sensors, however, the usual choice of electrodes remains poorly flexible metal electrodes, which greatly limits the overall flexibility of the sensors. In this work, we propose a flexible capacitive pressure sensor made entirely of thermoplastic polyurethane (TPU) and laser-induced graphene (LIG) derived from wood. The capacitive pressure sensor consisted of a flexible LIG/TPU electrode (LTE), a LIG/TPU electrode with micro hole array, and dielectric layer of TPU with micro-cone array molded from laser-engraved hole array on wood, which provided high sensitivity (0.11 kPa-1), ultra-wide pressure detection range (100Pa to 1.4MPa), fast response (~300 ms) and good stability (&gt;4000 cycles, at 0-35 kPa). We believe that our research makes a significant contribution to the literature because the easily available materials derived from wood and overall consistent flexibility meet the requirements of flexible electronic devices.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles in two widely used mouse models of septic cardiomyopathy, the cecal ligation and puncture (CLP) model and the lipopolysaccharide (LPS) model. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings suggested that 1) both methods can induce septic heart dysfunction within 24 hours; 2) distinct whole transcriptome expression profiles are revealed; 3) potentially different pathways are involved in causing heart failure in sepsis. The comprehensive comparison provides valuable insights into the molecular basis of septic cardiomyopathy and contributes to the ongoing search for effective treatment strategies, triggered by different factors for SICM.

Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated to severe human diseases. Although the physiological function of these proteins still elusive, their relation with neurodegeneration and cancer was clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules, to their involvement in tumor-related processes, and discuss the putative use of this proteins as cancer molecular biomarkers.

More than fifty million people over the age of fifty have osteoporosis issues due to low bone mass, disease contribution, and not exercising continuously. Certain most important risk factors and causes of osteoporosis contain age, gender, hormones, visits to inexperienced doctors, and certain medical conditions. In this manuscript, we diagnosed certain frank operational laws under the availability of complex intuitionistic fuzzy (CIF) information. Furthermore, using the evaluated operational laws, we pioneered the theory of CIF frank weighted averaging (CIFFWA), CIF frank ordered weighted averaging (CIFFOWA), CIF frank hybrid averaging (CIFFHA), CIF frank weighted geometric (CIFFWG), CIF frank ordered weighted geometric (CIFFOWG), CIF frank hybrid geometric (CIFFHG) operators, and described their beneficial and valuable results with certain useful properties. Moreover, we aim to evaluate the most dangerous type of osteoporosis based on their symptoms, causes, and risk factors using diagnosed approaches. Finally, to enhance the worth of the evaluated operators, we compare the diagnosed result with certain prevailing results and illustrated their geometrical representation with the help of MATLAB.

This article presents analysis of carbon Swan, C$_2$, laser-plasma emission records using line strength data, C$_2$-Swan-lsf, and the ExoMol astrophysical database. Line-strength data fitting of 0.25-nanometer spectral resolution ExoMol-computed spectra for a 6,000-Kelvin temperature C$_2$ Swan system, ${\rm d}\ ^3\,\Pi_{\rm g} \longrightarrow {\rm a} \ ^3\,\Pi_{\rm u}$, $\Delta {\rm v} = 0, \pm 1$, reveals a temperature of 5,640 Kelvin. The six per cent lower temperature is associated primarily with the accuracy of the transition wavelengths in the ExoMol vs. C$_2$-Swan-lsf data. The analysis of experiment data examines spectra that are recorded following laser-induced optical breakdown in carbon monoxide. The laser plasma data are recorded with 0.35-nm spectral resolution. The temperature inferences are elaborated when using non-linear fitting with both databases. The results show temperatures in excess of 6,000 Kelvin for the $\Delta {\rm v} = -1$ sequence, and for a time delay of 30\,$\upmu$s from laser plasma initiation. The accuracy of the C$_2$ Swan bands line strength data is of the order of 1 picometer. These line strength data are also utilized for analysis of laser-induced fluorescence experiments that employ a spectral resolution of 5.5 picometer, and a temperature of 2,716 Kelvin is inferred. Accurate C$_2$ databases show many applications in laboratory diagnosis and interpretation of astrophysical plasma records.

Abstract: Arranged patterns obtained by ultrafast laser processing on the surface of Ti/Cu/Ti/Si and Ti/Zr/Ti/Si thin film systems are reported. Two differently designed multilayer thin films, Ti/Cu/Ti/Si and Ti/Zr/Ti/Si, were deposited on silicon by the ion sputtering method. The bioactive surfaces on these systems involve the formation of laser-induced periodic surface structures (LIPSS) in each of the laser-written lines of mesh patterns on 5x5 mm areas. The formation of nano- and micro-patterns with an ultra-thin oxide film on the surfaces was used to observe the effects of morphology and proliferation of the MRC-5 cell culture line. To determine whether Ti-based thin films have a toxic effect on living cells, an MTT assay was performed. The relative cytotoxic effect as a percentage of surviving cells showed that there was no difference in cell number between the Ti-based thin films and the control cells. There was also no difference in the viability of the MRC-5 cells, except for the Ti/Cu/Ti/Si system, where there was a slight 10% decrease in cell viability.

This work communicates analysis of aluminum monoxide, AlO, laser-plasma emission records using line strength data and the ExoMol astrophysical database. A nonlinear fitting program computes comparisons of measured and simulated diatomic molecular spectra. Predicted cyanide spectra of the AlO, ${\rm B}\ ^2\,\Sigma^+ \longrightarrow {\rm X} \ ^2\,\Sigma^+$, $\Delta {\rm v} = 0, \pm 1, \pm 2, + 3$ sequences and progressions compare nicely with 1 nanometer resolution experimental results. The analysis discusses experiment data captured during laser ablation of Al$_2$O$_3$ with 266-nm, 6-mJ pulses. The accuracy of the AlO line strength data is better than one picometer. This work presents as well comparison of the $^{27}$Al$^{16}$O line strength and of ExoMol data for spectral resolutions of 0.1nm and 0.07nm. Accurate AlO databases show a volley of applications in laboratory and astrophysical plasma diagnosis.

Laser Direct Writing (LDW), also known as 3D multi-photon laser lithography of resins, is a promising technique for fabricating complex free-form elements, including micro-optical functional components. Regular organic or hybrid (organic-inorganic) resins are often used, with latter exhibiting better optical characteristics, as well as having the option to be heat-treated into inorganic glass-like structures, particularly useful for resilient micro-optics. While this work is a continuation of SZ2080™ calcination development , the Laser-Induced Damage Threshold (LIDT) of such sol-gel-derived glass micro-structures, particularly those that undergo heat treatment, has not been well-characterized. In this pilot study, we investigated the LIDT using the Series-on-One (S-on-1) protocol of functional micro-lenses produced via LDW and subsequently calcinated. Our results demonstrate that the LIDT can be significantly increased, even multiple times, by this approach, thus enhancing the resilience and usefulness of these free-form micro-optics. This work represents the first investigation in terms of LIDT into the impact of calcination on LDW produced sol-gel-derived glass micro-structures, and provides important insights for the development of robust micro-optical devices.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Typically, a diesel generator on the merchant ship, composed of a wound rotor synchronous generator and a four-stroke diesel engine, supplies electrical power to various loads. Recently, shaft generators for merchant vessels are increasingly replacing diesel generators to reduce CO2 emissions through fuel efficiency improvement. In particular, permanent magnet generators replace induction generators due to their high-efficiency characteristics at light loads. The surface-mounted permanent magnet can be a suitable rotor topology due to the relatively short constant power range. This generator can also operate as a motor according to the propulsion mode, so minimizing the harmonics of the induced voltage and the torque ripple is necessary. This paper proposes an alternative NdFeB magnet pole topology combined with the modular step-skewed rotor. The step-skewed rotor affects to reduce higher-order harmonics, and the modular pole reduces the permanent magnet assembly process and harmonics in voltage and torque. A 2-D finite element method is used to evaluate the harmonics of induced voltage and torque pulsation for the proposed topology. The topology shows harmonic minimization effect by comparing the characteristics of three flatted-bottom magnets. Compared to the tapered bread-loaf magnet, voltage harmonics to the 100th component are almost the same, and the torque ripple is reduced by more than 12% at the same residual flux density. The analysis method is verified by comparing test and analysis results for prototype machines with similar specifications.

For the replacement of lost contractile elements in the treatment of coronary heart disease, the most promising approaches to obtain cardiomyocytes by cardiac differentiation of pluripotent cells. The aim of this work is to develop a technology for the formation of a functional layer of cardiomyocytes differentiated from iPSCs, capable of generating rhythmic activity and synchronous contractions. To accelerate cardiomyocyte maturation, the renal subcapsular transplantation model was used in SCID mice. After explantation, the formation of cardiomyocyte contractile apparatus was assessed by fluorescence and electron microscopy, and calcium ion oscillation in the cytoplasm was assessed by visualization of the fluorescent calcium binding dye Fluo-8. It was shown that human iPSC-derived cardiomyocyte cell layers transplanted (for up to 6 weeks) under SCID mouse kidney fibrous capsules begin to form an ordered contractile apparatus and retain functional activity and the ability to oscillate calcium ion fluxes after explantation from the body.

A 3D graphene foam made of interconnected multilayer graphene flakes was produced on optical fibres (OF) by laser-induced transformation of a polyimide (PI) film coated on the OF cladding. This material, known as la-ser-induced graphene (LIG), was explored in the electrochemical detection and quantification of dopamine (DA) at physiologically relevant concentrations in the presence of the most relevant interfering molecules in biological fluids, ascorbic acid (AA) and uric acid (UA). The measured limit of detection is 100 nM, the linear range is 0.1 to 5 μM and a maximum sensitivity of 5.0 µA µM−1 cm−2 was obtained for LIG decorated with Pt nanoparticles (NPs). Moreover, immunity to AA and UA interference and to fouling was attained by decorating the LIG elec-trode with Pt NPs and coating with Nafion. These figures of merit underlines the potential of these sensors for the quantification of physiologically relevant concentrations of DA in biological fluids, paving the way for the development of hybrid electrochemical/optical sensing actuating platforms in a lab-on-fibre configuration, with relevant applications in biomedical engineering. The advantages of this hybrid arrangement include the possi-bility of in-situ counterproofing, extended measuring ranges, photoelectrochemical detection and the probing of inaccessible places. This elegant approach can also provide a simple and cost-effective way to fabricate biomed-ical devices with extended functionality, such as medical optical probes with added electrochemical capabilities, optogenetics combined with local electrochemical detection, among others.

The fall armyworm (FAW), Spodoptera frugiperda, has become one of the most important pests on corn in China since it invaded in 2019. Although FAW has not been reported to cause widespread damage to rice plants in China, it has been sporadically found feeding in the field. If FAW infests rice in China, the fitness of other insect pests on rice may be influenced. However, how FAW and other insect pests on rice interact remains unknown. In this study, we found that the infestation of FAW larvae on rice plants prolonged the developmental duration of the brown planthopper (BPH, Nilaparvata lugens (Stål)) eggs, and plants damaged by gravid BPH females did not induce defenses that influenced the growth of FAW larvae. Moreover, co-infestation by FAW larvae on rice plants did not influence the attractiveness of volatiles emitted from BPH-infested plants to Anagrus nilaparvatae, an egg parasitoid of rice planthoppers. FAW larvae were able to prey on BPH eggs laid on rice plants and grew faster compared to those larvae that lacked available eggs. Studies revealed that the delay in development of BPH eggs on FAW-infested plants was probably related to the increase in levels of jasmonoyl-isoleucine, abscisic acid and the defensive compounds in the rice leaf sheaths on which BPH eggs were laid. These findings indicate that if FAW invades rice plants in China, the population density of BPH may be decreased by intraguild predation and induced plant defenses, whereas the population density of FAW may be increased.

Differentiation of induced pluripotent stem cells to a range of useful, mature target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, organoids expressed ACE2 capable of binding SARS-Cov2 spike protein demonstrating the physiological relevance of the organoids produced. This study demonstrates the rapid production of pulmonary organoids using a multi-germ layer approach that could be used for studying novel respiratory disease interactions.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

Cotton (Gossypium spp.) is a major source of natural fiber and an important cash crop. The cotton growth habit and architecture determine its productivity and influence management strategies for commercial production. The GATA transcription factors (TFs) control various developmental processes in plants, such as flower, bract and embryo development, and petal differentiation. As stable transformation is still a bottleneck in many plant species, TRV-VIGS was used to manipulate gene expression in different plants, including Gossypium hirsutum L. In this study, we undertook the TRV-based VIGS to functionally characterize two candidate genes, Gohir.D05G103700 and Gohir.D12G153600, identified through the expression QTL analysis for five floral induction and meristem identity genes using the upland cotton mini-core collection. Virus-induced silencing of the Gohir.D05G103700 gene resulted in up to a 1.4-fold reduction in the transcript level in two inoculated plants, G3 and G4, and Gohir.D12G153600 gene resulted in up to a 2.3-fold reduction in transcript level in a single inoculated plant P05 relative to the mock-treated plant. The TRV2-Gohir.D05G103700 inoculated plants precisely G3 and G4 also exhibited loss of the supernumerary (fourth) floral bract in the squares, whereas the TRV2-Gohir.D12G153600 inoculated plants did not show any observable phenotypic change relative to the mock-treated plants.  Altogether, this study suggested that TRV-VIGS can be used to characterize genes in cotton relatively rapidly and the cotton Gohir.D05G103700 gene is a positive regulator of the indeterminate growth habit in cotton, which could be manipulated to obtain a cotton plant with architecture best suited for the cultivation area.

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

Heavy metal contamination is listed among the most alarming threats to the environment and human health. The detrimental effects of heavy metals in the natural environment span from a reduction of biodiversity to toxic effects on marine life - through microplastic born heavy metals -, to impairment of microbial activity in the soil, and to detrimental effects on animal reproduction. A host of different chemical and biological technologies have been proposed to alleviate environmental contamination by heavy metals. Relatively less attention has been paid to the microbial precipitation of heavy metals, as a side mechanism of the most general process of microbially induced calcite precipitation (MICP). This process is currently receiving a great deal of interest from both a theoretical and practical standpoint, because of its possible practical applications in concrete healing and soil consolidation, and its importance in the more general framework of microbial induced mineral precipitation. In this study, we analyse the ability of the marine bacteria Vibrio harveyi in co-precipitating CaCO3 minerals, together with Cd, Cr, Pb, and Zn added in form of nitrates, from solutions containing CaCl2. The precipitated carbonatic minerals were a function of the different heavy metals present in the solution. The process of co-precipitation appears to be rather effective and fast, as the concentrations of the 4 heavy metals were reduced in 2 days by 97.2%, on average, in the solutions.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

This work discusses diatomic molecular spectroscopy of laser-induced plasma and analysis of data records, specifically signatures of cyanide, CN. Line strength data from various databases are compared for simulation of the CN, B2Σ+⟶X2Σ+, Δv=0 sequence. Of interest are recent predictions using an astrophysical database, i.e., ExoMol, a laser-induced fluorescence database, i.e., LIFBASE, and a program for simulating rotational, vibrational and electronic spectra, i.e., PGOPHER. Cyanide spectra that are predicted from these databases are compared with line strength data that are in use by the author for the last three decades in the analysis of laser-plasma emission spectra. Comparisons with experimental laser-plasma records are communicated as well, and for spectral resolutions of 33 and 110 picometer. The accuracy of the CN line strength data is better than one picometer. Laboratory experiments utilize 308-nm, 35-picosecond bursts within an overall 1-nanosecond pulse-width, and 1064-nm, 6-ns pulse-width radiation. Experimental results are compared with predictions. Differences of the databases are elaborated for equilibrium of rotational and vibrational modes and at an internal, molecular temperature of the order of 8,000 Kelvin. Applications of accurate CN data include for example combustion diagnosis, chemistry, and supersonic and hypersonic expansion diagnosis. The cyanide molecule is also of interest in the study of astrophysical phenomena.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

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.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study we investigate the clinical use in these directions of a “damage” type biomarker - Neutrophil Gelatinase-Associated Lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasmsa NGAL was determined at baseline, at 4 and 24 hours after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (132.33±72.83 ng/ml versus 111.48±65.06 ng/ml, p=0.006) and at the 24th hour (212 .93±276.61 ng/ml, p=0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (128.18±99 ng/ml, p=0.002) and reached levels close to those in patients with CI-AKI. Unlike new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good - AUC 0.847 (95% CI: 0.677-1.000; p=0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539 – 0.924; p=0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

Longitudinal image registration of pulmonary computed tomography (PCT) images may serve as an essential tool for investigating the relationship between radiation dose distribution and the occurrence and phenotype of radiation-induced lung disease (RILD). Although numerous longitudinal registration algorithms have been developed for PCT, most similarity-based approaches are not suitable for PCT involving RILD due to the complex tissue variation between two PCT images. Moreover, conventional feature-based approaches might fail to find a sufficient number of matched pairs of feature points due to the disparate lung deformation caused by breathing and RILD. To overcome the challenges resulting from RILD, component structure coherence point drift (CSCPD) was proposed to establish a deformation model by decomposing the chest into several components and matching them with individual parameters based on coherence point drift (CPD). Moreover, a regional vascular point matching (RVPM) algorithm was proposed to generate a vascular subtree and to substantially increase the number of corresponding pairs between two images. Eventually, the components were recomposed and aligned by a thin plate spline algorithm. A performance assessment on 15 pairs of PCT images of patients with RILD yielded recall and precision values of 0.85 and 0.89 for RVPM, respectively. Moreover, the target registration error of CSCPD with RVPM (2.3 ± 1.79) was significantly better than that of conventional CPD with RVPM (2.95 ± 1.89) and conventional CPD (5.04 ± 2.87). Therefore, the proposed registration system is robust enough to address the disparate deformation of lungs with RILD, and it improves registration accuracy within the parenchyma.

This work communicates line strength data and associated scripts for computation and spectroscopic fitting of selected transitions of the diatomic molecules AlO, C2, CN, OH, N2+, NO, and TiO. For ease of use, the scripts for data analysis are designed for inclusion in various software packages or program languages. The accuracy of the data is of the order of less than one picometer, suitable for analysis of laser-induced fluorescence and laser-plasma spectra. Selected results demonstrate the applicability of the program for data analysis in laser-induced optical breakdown spectroscopy primarily at The University of Tennessee Space Institute, Center for Laser Applications. Representative spectra are calculated and referenced to measured data records.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via an in vitro function assay in an in vivo Panc02 cell–bearing mouse model. We established an in vitro culture assay for CIK cells and determined the proportions of different peripheral lymphocytes. The antitumor effect of the combination of IRE and CIK cells in a Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model was investigated; tumor size and mouse survival rates were recorded. We used flow cytometry (FCM) to analyze the proportion of intratumoral lymphocytes, the expression of chemokine receptors, and the proliferative activity of CIK cells. The proportion of cells that were positive for clusters of differentiation 3 and 8 (CD3+CD8+) and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined IRE/CIK cell treatment significantly inhibited tumor growth and increased the survival rate of Panc02 cell–bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by, and the proliferative activity of, CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC subcutaneous-xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and of regulators of CIK cell proliferation.

Fiber aggregation in nanocomposites has an important effect on the macroscopic electrical performance. To quantitatively evaluate its effect, an index to characterize the degree of aggregation is imperative, and ideally it should have three features simultaneously, i.e., single-parametric, dimensionless and physically meaningful, applicable to different aggregation topologies, and one-to-one corresponding to material electrical properties. To this end, a new aggregation degree is proposed, which is defined as the average increased number of fibers that connect with each one when fibers aggregate from a uniformly distributed state. This index is applicable to different aggregation topologies from lump-like aggregating clusters to network-like aggregating clusters. This index is proven to only depend on the local features of aggregating clusters, and can be concisely expressed by the characteristic parameters of local structure, via geometric probability analysis and numerical validations. Further, a one-to-one linear relation between the aggregation degree and percolation threshold is established by Monte Carlo simulations, which is independent of the distribution law of the fibers. This work provides a guide to the property characterization, performance prediction and material design of nanocomposites, and also gives a physical insight into the understanding of systems with similar non-uniform distributions.

This study presents the developments regarding the time-domain-induced polarisation method, as a supporting tool for resistivity soundings during investigations of coastal detrital aquifers that are salinised by marine intrusion. The interpretation of resistivity measurements in such aquifers, which have variable hydrochemistry and lithology, involves uncertainties owing to the presence of low-resistivity lithologies, such as clays. To reduce these uncertainties, the use of other geophysical parameters is necessary; hence, this study focuses on induced polarisation, since it can be measured simultaneously with resistivity. In detail, we propose the determination of induced polarisation using 1D techniques, while developing a different algorithm for processing the induced polarisation data. The aim is to extend the results of this phenomenon, using instead of chargeability, the concepts of polarisability and decay time, which are extracted from the decay curve, given that they represent more intrinsic properties of the various analysed subsurface media. We present results obtained by applying this methodology to a Quaternary aquifer of the Costa del Sol in the SE Iberian Peninsula (in the province of Almería) during two different campaigns, one before and one after winter (i.e., in October and February, respectively). The results reveal the position of the saline front during each campaign, while reflecting the seasonal movement of the marine intrusion.

This paper develops the study of the effect of powerful ultrasound on the laser breakdown of liquids and a comparative study of the possibilities of acoustic and optical diagnostics of breakdown. The method of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of liquids, along with high efficiency, continues to be less sensitive compared to traditional chemical methods. The paper develops a method of using additional ultrasound irradiation of the laser breakdown area in order to increase the efficiency of LIBS. Using the developed technique, spectral lines of chemical elements such as potassium, manganese, sodium, calcium, etc. were obtained for the first time depending on the frequency and power of ultrasound. It is shown that a sharp increase in the intensity of spectral lines of elements in water during laser breakdown is observed in the field of high-power ultrasound. It indicates an increase in the sensitivity of the combined method of ultrasonic LIBS. Along with the optical spectrum, the spectral and energy characteristics of acoustic emission were studied. An automated complex for hydrophysical and spectral studies is described, which was tested in the Sea of Japan during the voyage No. 81 of the research vessel RV "Professor Gagarinsky" in August 2022.

Prior studies have focused on the overall behavior of randomly moving particle swarms. However, the characteristics of the stochastic-constrained particles that form ubiquitously within these swarms remain oblivious. This study demonstrates a generalized diffusion equation for stochastic-constrained particles that considers the velocity and location aggregation effects observed from their parent particle swarm (i.e., a completely random particle swarm). This equation can be approximated as the form of Schr\"odinger equation in the microcosmic case (low relative density) and describe the dynamics of the total mass distribution in the macrocosmic case (high relative density). The predicted density distribution of the particle swarm in the stable aggregation state is consistent with the total mass distribution of massive, relaxed galaxy clusters (at least in the range of r < r_s), preventing cuspy problems in the empirical Navarro-Frenk-White (NFW) profile. This study opens a window to observe the dynamics of stochastic-constrained particles from a third perspective, from which the aggregation effect of particles without gravitation can be saw.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

Objectives: Although pitch reception poses a great challenge for individuals with cochlear implants (CIs), formal auditory training (e.g., high variability phonetic training, HVPT) has been shown to provide direct benefits in pitch-related perceptual performances such as lexical tone recognition for CI users. As lexical tones in spoken language are expressed with a multitude of distinct spectral, temporal, and intensity cues, it is important to determine the sources of training benefits for CI users. The purpose of the present study was to conduct a rigorous fine-scale evaluation with the categorical perception (CP) paradigm to control the acoustic parameters and test the efficacy and sustainability of HVPT for Mandarin-speaking pediatric CI recipients. The main hypothesis was that HVPT-induced perceptual learning would greatly enhance CI users’ ability to extract the primary pitch contours from spoken words for lexical tone identification and discrimination. Furthermore, individual differences in immediate and long-term gains from training would likely be attributable to baseline performance and duration of CI use. Design: Twenty-eight prelingually deaf Mandarin-speaking kindergarteners with CIs were tested. Half of them received five sessions of HVPT within a period of three weeks. The other half served as control who did not receive the formal training. Two classical CP tasks on a tonal continuum from Mandarin Tone 1 (high-flat in pitch) to Tone 2 (mid-rising in pitch) with fixed acoustic features of duration and intensity were administered before (pretest), immediately after (posttest), and 10 weeks post training termination (follow-up test). Participants were instructed to either label a speech stimulus along the continuum (i.e., identification task) or determine whether a pair of stimuli separated by zero or two steps from the continuum was the same or different (i.e., discrimination task). Identification function measures (i.e., boundary position and boundary width) and discrimination function scores (i.e., between-category score, within-category score, and peakedness score) were assessed for each child participant across the three test sessions.Results: Linear mixed-effects (LME) models showed significant training-induced enhancement in lexical tone categorization with significantly narrower boundary width and better between-category discrimination in the immediate posttest over pretest for the trainees. Furthermore, training-induced gains were reliably retained in the follow-up test 10 weeks after training. By contrast, no significant changes were found in the control group across sessions. Regression analysis confirmed that baseline performance (i.e., boundary width in the pretest session) and duration of CI use were significant predictors for the magnitude of training-induced benefits. Conclusions: The stringent CP tests with synthesized stimuli that excluded acoustic cues other than the pitch contour and were never used in training showed strong evidence for the efficacy of HVPT in yielding immediate and sustained improvement in lexical tone categorization for Mandarin-speaking children with CIs. The training results and individual differences have remarkable implications for developing personalized computer-based short-term HVPT protocols that may have sustainable long-term benefits for aural rehabilitation in this clinical population.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Most neurodegenerative diseases have the characteristics of proteinopathies, i.e. they cause lesions to appear in vulnerable regions of the nervous system, corresponding to protein aggregates that progressively spread through the neuronal network as the symptoms progress. Alzheimer's disease is one of these proteinopathies. It is characterized by two lesions, neurofibrillary tangles (NFTs) and senile plaques, formed essentially of amyloid peptides (Aβ). A combination of factors ranging from genetic mutations to age-related changes in the cellular context converge in this disease to accelerate Aβ deposition. Over the last two decades, numerous studies have attempted to elucidate how structural determinants of its precursor (APP) modify Aβ production, and to understand the processes leading to the formation of different Aβ aggregates; e.g. fibrils and oligomers. The synthesis proposed in this review indicates that the same motifs can control APP function and Aβ production essentially by regulating membrane dimerization, and subsequently Aβ aggregation processes. The distinct properties of these motifs and the cellular context regulate the APP conformation to trigger the transition to the amyloid pathology. This concept can be transposed to the study of other proteinopathies, providing a framework for improving our understanding of these mechanisms that devastate neuronal functions.

Proteomic analysis revealed the preservation of many proteins in the “Heslington brain” (which is at least 2,600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins (“main proteins”), heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein are engaged in the formation non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as “main proteins” and their 44 interactors, as well as all other protein identified in the Heslington brain. These analyses revealed that all five “main proteins”, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining proteins are expected to contain sizable disordered regions. This is in contrary the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.