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NADPH oxidases (NOX's), and the reactive oxygen species (ROS) they produce, play an important role in host defense, thyroid hormone synthesis, apoptosis, gene regulation, angiogenesis and other processes. However, overproduction of ROS by these enzymes is associated with cardiovascular disease, fibrosis, traumatic brain injury (TBI) and other diseases. Structural similarities between NOX's have complicated development of specific inhibitors. Here, we report development of NCATS-SM7270, a small molecule optimized from GSK2795039, that inhibited NOX2 in primary human and mouse granulocytes. NCATS-SM7270 specifically inhibited NOX2 and had reduced inhibitory activity against xanthine oxidase in vitro. We also studied the role of several NOX isoforms during mild TBI (mTBI) and demonstrated that NOX2 and, to a lesser extent, NOX1 deficient mice are protected from mTBI pathology, whereas injury is exacerbated in NOX4 knockouts. Given the pathogenic role played by NOX2 in mTBI, we treated mice transcranially with NCATS-SM7270 after injury and revealed a dose-dependent reduction in mTBI induced cortical cell death. This inhibitor also partially reversed cortical damage observed in NOX4 deficient mice following mTBI. These data demonstrate that NCATS-SM7270 is an improved and specific inhibitor of NOX2 capable of protecting mice from NOX2-dependent cell death associated with mTBI.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

BackgroundFecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated.Hypothesis/objectivesDetermine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs.AnimalsTen client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors.MethodsProspective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR.ResultsNo significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention.Conclusions and clinical importanceFecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

Granulibacter bethesdensis can infect patients with chronic granulomatous disease, an immunodeficiency caused by reduced phagocyte NADPH oxidase function. Intact G. bethesdensis (Gb) is hypostimulatory compared to Escherichia coli, i.e., cytokine production in human blood requires 10–100 times more G. bethesdensis CFU/mL than E. coli. To better understand the pathogenicity of G. bethesdensis, we isolated its lipopolysaccharide (GbLPS) and characterized its lipid A. Unlike with typical Enterobacteriaceae, the release of presumptive Gb lipid A from its LPS required a strong acid. NMR and mass spectrometry demonstrated that the carbohydrate portion of the isolated glycolipid consists of α-Manp-(1→4)-β-GlcpN3N-(1→6)-α-GlcpN-(1⇿1)-α-GlcpA tetra-saccharide substituted with five acyl chains: the amide-linked N-3′ 14:0(3-OH), N-2′ 16:0(3-O16:0), and N-2 18:0(3-OH) and the ester-linked O-3 14:0(3-OH) and 16:0. The identification of glycero-d-talo-oct-2-ulosonic acid (Ko) as the first constituent of the core region of the LPS that is covalently attached to GlcpN3N of the lipid backbone may account for the acid resistance of GbLPS. In addition, the presence of Ko and only five acyl chains may explain the >10-fold lower proinflammatory potency of GbKo–lipidA compared to E. coli lipid A, as measured by cytokine induction in human blood. These unusual structural properties of the G.bethesdensis Ko–lipid A glycolipid likely contribute to immune evasion during pathogenesis and resistance to antimicrobial peptides.

Preclinical biomedical research is limited by the predictiveness of in vivo and in vitro models. While in vivo models offer the most complex system for experimentation, they are also limited by ethical, financial, and experimental constraints. In vitro models are simplified models that do not offer the same complexity as living animals but do offer financial affordability and more experimental freedom; therefore, they are commonly used. Traditional 2D cell lines cannot fully simulate the complexity of the epithelium of healthy organs and limit scientific progress. The One Health Initiative was established to consolidate human, animal, and environmental health while also tackling complex and multifactorial medical problems. Reverse translational research allows for the sharing of knowledge between clinical research in veterinary and human medicine. Recently, organoid technology has been developed to mimic the original organs epithelial microstructure and function more reliably. While human and murine organoids are available, numerous other organoids have been derived from traditional veterinary animals and exotic species in the last decade. With these additional organoid models, species previously excluded from in vitro research are becoming accessible, therefore unlocking potential translational and reverse translational applications of animals with unique adaptations that overcome common problems in veterinary and human medicine.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Diabetes mellitus (DM) is a common chronic metabolic disease in humans and household cats that is characterized by persistent hyperglycemia. DM is associated with dysfunction of the intestinal barrier. This barrier is comprised of an epithelial monolayer that contains a network of tight junctions that adjoin cells and regulate paracellular movement of water and solutes. The mechanisms driving DM-associated barrier dysfunction are multifaceted, and the direct effects of hyperglycemia on the epithelium are poorly understood. Preliminary data suggest that fenofibrate, An FDA-approved peroxisome proliferator-activated receptor-alpha (PPARα) agonist drug attenuates intestinal barrier dysfunction in dogs with experimentally-induced DM. We investigated the effects of hyperglycemia-like conditions and fenofibrate treatment on epithelial barrier function using feline intestinal organoids. We hypothesized that glucose treatment directly increases barrier permeability and alters tight junction morphology, and that fenofibrate administration can ameliorate these deleterious effects. We show that hyperglycemia-like conditions directly increase intestinal epithelial permeability, which is mitigated by fenofibrate. Moreover, increased permeability is caused by disruption of tight junctions, as evident by increased junctional tortuosity. Finally, we found that increased junctional tortuosity and barrier permeability in hyperglycemic conditions were associated with increased protein kinase C-α (PKCα) activity, and that fenofibrate treatment restored PKCα activity to baseline levels. We conclude that hyperglycemia directly induces barrier dysfunction by disrupting tight junction structure, a process that is mitigated by fenofibrate. We further propose that counteracting modulation of PKCα activation by increased intracellular glucose levels and fenofibrate is a key candidate regulatory pathway of tight junction structure and epithelial permeability.

In this research, a meta-analysis study was conducted to determine the effect of student and teacher-centered practices in science lessons on students' scientific process skills. To this end, the literature related to the studies conducted in Turkey and abroad was searched. For this purpose, articles, master's, and doctoral theses published between 1999-2020 in national and international databases were scanned. As a result of the literature review, it was deemed appropriate to include a total of 100 studies in the meta-analysis. In the meta-analysis study, subgroup analysis was performed in the fields of science, publication year, education levels, sample size, application period and publication types. As a result of the meta-analysis, it was determined that student-centered practices had a positive effect on students' SPS in science lessons compared to teacher-centered ones. It was also found out that 93 of the 100 studies included in the study had a positive effect size and 7 had a negative effect size value. Of the positive studies, 6 were at the level of weak effect, 23 at the level of small effect, 21 at the level of medium effect, and 43 at the level of large effect. In light of the findings obtained, student-centered practices in science education appear to have a stronger effect on developing students' scientific process skills than teacher-centered practices.

BackgroundCytosine arabinoside (Ara-C) is a nucleoside analog prodrug utilized for immunomodulatory effects mediated by its active metabolite Ara-CTP. Optimal dosing protocols for immunomodulation in dogs have not been defined. Cytarabine ocfosfate (CO) is a lipophilic prodrug of Ara-C that can be administered PO and provides prolonged serum concentrations of Ara-C.ObjectivesProvide pharmacokinetic data for orally administered CO and determine accumulation and functional consequences of Ara-CTP within peripheral blood leukocytes.AnimalsThree healthy female hound dogs and 1 healthy male Beagle.MethodsProspective study. Dogs received 200 mg/m2 of CO PO q24h for 7 doses. Serum and cerebrospinal fluid (CSF) CO and Ara-C concentrations were measured by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Complete blood counts, flow cytometry, and leukocyte activation assays were done up to 21 days. Incorporation of Ara-CTP within leukocyte DNA was determined by LC-MS/MS.ResultsMaximum serum concentration (Cmax ) for Ara-C was 456.1-724.0 ng/mL (1.88-2.98 μM) and terminal half-life was 23.3 to 29.4 hours. Cerebrospinal fluid: serum Ara-C ratios ranged from 0.54 to 1.2. Peripheral blood lymphocyte concentrations remained within the reference range, but proliferation rates poststimulation were decreased at 6 days. Incorporation of Ara-CTP was not saturated and remained >25% of peak concentration at 13 days.Conclusions and clinical importanceOral CO may produce prolonged serum Ara-C half-lives at concentrations sufficient to induce functional changes in peripheral leukocytes and is associated with prolonged retention of DNA-incorporated Ara-CTP. Application of functional and active metabolite assessment is feasible and may provide more relevant data to determine optimal dosing regimens for Ara-C-based treatments.

The aim of this case series was to describe the pulmonary rehabilitation experience of our clinic the treatment of patients with post-Covid-19. Fever, cough, fatigue, anorexi, shortness of breath, myalgia, disability and anxiety occurs in most cases. We report 6 cases of patients with Covid-19 who applied to our clinic from the chest diseases clinic that illustrate the various indications for physical therapy, clinical challenges, potential treatment methods, and short-term response to treatment. Spirometry, 6 min walking test (6MWT), short physical performance battery, The Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT), beck anxiety-depression scale and short form of health‐related quality of life scale (SF‐36) were applied to the patients before and after pulmonary rehabilitation. The pulmonary rehabilitation program in Covid-19patients ranged from patient education, aerobic exercise, mobilization, and respiratory therapy. After pulmonary rehabilitation, patients had improved symptoms of dyspnea, relieved anxiety, reduced complications, minimized disability, improved function, and improved quality of life. Pulmonary rehabilitation interventions will be required in the post-Covid-19 patients at the appropriate time.

Abstract We determine the gravito-magnetic Love numbers of non-rotating black holes in all spacetime dimensions through a novel and direct derivation. The Ishibashi-Kodama master field and its associated field equation are avoided. The matching to the EFT variables is simple. This method allows us to correct the values in the literature. Moreover, we highlight a parity-based selection rule for nonlinear terms that include both electric-type and magnetic-type gravitational field tensors, enabling us to conclude that many of the nonlinear response coefficients in the Schwarzschild black hole effective action vanish.

Preschool education encompasses a period when children are at their highest capacity of learning, and when their lives are being shaped. Today, television plays an important role in child's development. Numerous studies reveal that the content of the programs watched by children are as important as determining the time spent by the children for televiewing. The purpose of this research is to examine the effects of cartoons, intended for preschoolers, on the children's development under the predetermined criteria. The research was carried out by descriptive scanning method based on document review. The study material of this research consisted of randomly selected episodes of 71 cartoons claimed to have been prepared for early childhood. The data collection tool was the Cartoon Checklist which was developed by the researcher. According to the data obtained from the research it is seen that the graphics, sound and music used in 66 of the cartoons are completely or partially appropriate. However, it is seen that the dialogues used in 65 cartoons, content used in 57 cartoons, objects used in 55 cartoons, and elements of Turkish culture in 26 cartoons are completely or partially suitable for the child.

Summary: Dictyostelium discoideum is a professional phagocyte frequently used to study cellular processes underlying the recognition, engulfment, and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control membrane properties, participate in signal transmission, and serve as adhesion molecules in recognition processes relevant to immunity and infection. By combining lipidomics with a bioinformatics-based cloning strategy, we show here that D. discoideum produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones. Cell-free expression of candidate inositol-phosphorylceramide (IPC) synthases from D. discoideum enabled identification of an enzyme that selectively catalyzes the transfer of phosphoinositol from phosphatidylinositol onto ceramide. The IPC synthase, DdIPCS1, shares multiple sequence motifs with yeast IPC and human sphingomyelin synthases and localizes to the Golgi apparatus as well as the contractile vacuole of D. discoideum. These findings open up important opportunities for exploring a role of sphingolipids in phagocytosis and infection across major evolutionary boundaries.

Chronic granulomatous disease (CGD) is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patients with CGD from North and Central America. Genomic typing showed that 3 patients had recurrent infection months to years after apparent clinical cure. Two patients were infected with the same strain as previously isolated, and 1 was infected with a genetically distinct strain. This organism is multidrug resistant, and therapy required surgery and combination antimicrobial drugs, including long-term ceftriaxone. G. bethesdensis causes necrotizing lymphadenitis in CGD, which may recur or relapse.

Abstract Background Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra‐gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. Hypothesis/Objectives Determine the short‐term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. Animals Ten client‐owned, clinically healthy dogs as FMT recipients, and 2 client‐owned clinically healthy dogs as FMT donors. Methods Prospective non‐randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self‐reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. Results No significant changes were found in the following variables: CBC, serum biochemistry, C‐reactive protein, serum cytokines (interleukins [IL]‐2, ‐6, ‐8, tumor necrosis factor [TNF]‐α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. Conclusions and Clinical Importance Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short‐term.

Abstract Coronavirus and other prevailing viruses continue to remain a health threat and challenge the efforts of institutions to promote vaccination acceptance. The current study’s aim is to propose a conceptual framework explaining the role of individual motivators (such as self-interest and collective interest) in shaping attitudes toward vaccination while emphasizing the pivotal role of institutional trust as a mediator and gender as a moderator. Data were collected via an online panel survey among Israelis (N = 464), and SEM statistics were used to test the model empirically. The path analysis model supports the positive direct effect of collective interest and the negative effect of self-interest. Additionally, it shows an indirect effect through the mediation effect of institutional trust and gender moderation. Therefore, institutional trust may significantly influence self-interest people’s attitudes toward vaccines. Furthermore, since females process information more comprehensively, their developed trustworthiness in institutions has an increased impact on vaccine acceptance. Theoretical and practical implications are discussed.

Mast cell tumor (MCT) is a common skin cancer in dogs that has a wide range of clinical behaviors. The purpose of this study was to develop a novel multicolor flow cytometry (FC) panel that will enable the quantification of candidate prognostic markers (Ki-67 and pKIT) in fine needle aspirate (FNA) samples prior to surgical removal of the tumors. FNA of canine MCTs and the NI-1 cell line were utilized to develop a FC panel that includes a viability dye (FVS620, BD Biosciences; 7-AAD, Invitrogen) and the following primary conjugated antibodies: CD117-PE (ACK45, BD Biosciences), pKIT-A647 (polyclonal bs-3242R, BIOSS) and Ki-67-FITC (20Raj1, eBioscience; MIB-1, DAKO). A total of nine FNA samples of canine MCTs were collected, seven out which produced sufficient cells for FC analysis. The Ki-67 antibody clone 20Raj1 produced a positive signal when applied to blood leukocytes but failed to provide robust labeling of neoplastic mast cells. The Ki-67 antibody clone MIB-1 delivered a superior staining quality in both the NI-1 cells and primary MCT cells. CD117-PE signal was adequate post fixation and permeabilization and in the combination of 7-AAD. pKIT produced non-specific staining and was not suitable for this multicolor FC panel. In conclusion, FNA samples of canine MCTs can often yield adequate cell numbers for FC analysis, and a multicolor FC panel was developed that can detect Ki-67 in canine mast cells. This would permit further studies into the potential use of this panel for canine cutaneous and subcutaneous MCT prognostication purposes.

The potential of mesenchymal stem cells (MSCs) for tissue repair and regeneration has garnered great attention. While MSCs are likely to interact with microbes at sites of tissue damage and inflammation, like in the gastrointestinal system, the consequences of pathogenic association on MSC activities have yet to be elucidated. This study investigated the effects of pathogenic interaction on MSC trilineage differentiation paths and mechanisms using model intracellular pathogen Salmonella enterica ssp enterica serotype Typhimurium. The examination of key markers of differentiation, apoptosis, and immunomodulation demonstrated that Salmonella altered osteogenic and chondrogenic differentiation pathways in human and goat adipose-derived MSCs. Anti-apoptotic and pro-proliferative responses were also significantly upregulated (p < 0.05) in MSCs during Salmonella challenge. These results together indicate that Salmonella, and potentially other pathogenic bacteria, can induce pathways that influence both apoptotic response and functional differentiation trajectories in MSCs, highlighting that microbes have a potentially significant role as influencers of MSC physiology and immune activity.

In this research, a meta-analysis was conducted to find out the effect level of STEM education on students' academic achievement in science courses. Scientific studies which were conducted and published in Turkey between January 2018 and March 2020 were reviewed in the research. As a result of the literature review, 54 studies that were suitable for the purpose of the study were reached. In analyses conducted with a statistical analysis program, effect levels were compared in terms of subject area and number of participants in addition to approaches/method used. According to the results of this research, it was concluded that STEM education was more effective in increasing students' achievement in science courses when compared with teacher-centred teaching methods. According to the results examined according to other variables discussed in the research, significant difference was found in terms of the year in which the study was conducted, the researcher's job, application period of the study and the number of participants. According to the results of the examined variables, the largest effect size was found in the field of biology, at high school level, doctoral publications, in researchers who were teachers, with 81 and above participants, in studies conducted in 2019.

For students of English for Academic Purposes (EAP), reading articles in their field of study in English is particularly challenging. One of their main difficulties is understanding unfamiliar words. The purpose of this study was to compare the effect of online monolingual and bilingual dictionary tools on reading comprehension in English and check student preference for one or the other tool. The study was conducted in an advanced English class for tertiary students of government. Two online dictionary tools were used: Reverso, a bilingual tool, and Rewordify, a monolingual tool. These tools allow for more immediacy and speed than previous dictionary tools. The instructor taught students how to use the tools, and after a few practice sessions, two reading comprehension quizzes were administered. The texts for the quizzes were approximately the same length and reading level, and the questions were objective and parallel. Students used Reverso for one of the quizzes and Rewordify for the other and answered a short attitude questionnaire after each quiz. Results show that students got higher grades using the bilingual dictionary tool and felt it was more helpful. Based on the results, we believe language teachers should consider making students aware of the new tools available.

Microwave (MW) treatment is an environmentally friendly and time-saving technique with great potential for generating wood-impregnation innovations. In this study, a microwave-assisted impregnation (MWAI) approach was developed to achieve adequate retention and fixing of alkaline copper quaternary (ACQ) in refractory spruce wood. The synergistic effect of MW pre- and post-treatments in the impregnation procedure on wood's compressive strength (CS) and copper leaching resistance and valence conversion was investigated. In conclusion, high-intensity MW pre-treatment and low-intensity MW post-treatment provided optimum results for the fixation of copper. Based on the results of the copper conversion assays, the same MWAI procedure is also predicted to give high biological efficiency.

This paper presents a detailed analysis of the free and random vibrations of an all-side-clamped spherical sandwich shell. The sandwich is composed of graphite-epoxy layers, each consisting of four laminas with different fiber orientations and an isotropicKevlar 29 core layer. The study employs the First-Order Shear Deformation Theory (FSDT) to establish kinematic relations and Hamilton’s principle to derive the equations of motion. The sandwich shell is discretized,and equations of motion are reduced to algebraicequationsusing the Differential Quadrature Method (DQM). Natural frequencies are found and subsequently, the GeneralizedAlpha Method is applied to solve the random forced vibration problem. To validate the accuracy of the results, a comparison is made with solutions obtained using the ABAQUS software.

Abstract Diabetes mellitus (DM) is a common chronic metabolic disease in humans and household cats that is characterized by persistent hyperglycemia. DM is associated with dysfunction of the intestinal barrier. This barrier is comprised of an epithelial monolayer that contains a network of tight junctions that adjoin cells and regulate paracellular movement of water and solutes. The mechanisms driving DM-associated barrier dysfunction are multifaceted, and the direct effects of hyperglycemia on the epithelium are poorly understood. Preliminary data suggest that fenofibrate, An FDA-approved peroxisome proliferator-activated receptor-alpha (PPARα) agonist drug attenuates intestinal barrier dysfunction in dogs with experimentally-induced DM. We investigated the effects of hyperglycemia-like conditions and fenofibrate treatment on epithelial barrier function using feline intestinal organoids. We hypothesized that glucose treatment directly increases barrier permeability and alters tight junction morphology, and that fenofibrate administration can ameliorate these deleterious effects. We show that hyperglycemia-like conditions directly increase intestinal epithelial permeability, which is mitigated by fenofibrate. Moreover, increased permeability is caused by disruption of tight junctions, as evident by increased junctional tortuosity. Finally, we found that increased junctional tortuosity and barrier permeability in hyperglycemic conditions were associated with increased protein kinase C-α (PKCα) activity, and that fenofibrate treatment restored PKCα activity to baseline levels. We conclude that hyperglycemia directly induces barrier dysfunction by disrupting tight junction structure, a process that is mitigated by fenofibrate. We further propose that counteracting modulation of PKCα activation by increased intracellular glucose levels and fenofibrate is a key candidate regulatory pathway of tight junction structure and epithelial permeability.