Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of Glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that inhibition of GPx4 by RAS Selective Lethal Compound 3 (RSL3) generated an increase in reactive oxygen species (ROS), increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, an inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knock-down. The intracellular calcium chelator BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which in turn stimulate the production of ROS and induce lipid peroxidation and ferroptotic cell death in a noxious positive feedback cycle.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

The vibrational excitation cross section of a diatomic molecule by positron impact is obtained using wavepacket propagation techniques. The dynamics was carried on a two-dimensional potential energy surface which couples a hydrogen-like harmonic oscillator to a positron via a spherically symmetric correlation polarization potential. The cross section for the excitation of the first vibrational mode is in good agreement with previous reports. Our model suggests that a positron couples to the target vibration by responding instantly to an interaction potential which depends on the target vibrational coordinate.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

Erastin (ER) induces cell death by utilizing the process of ferroptosis via generation of reactive oxygen species (ROS). Ferroptosis is characterized by accumulation of ROS within the cell, leading to an iron-dependent oxidative damage-mediated cell death. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of ER in K-RAS mutant human ovarian tumor OVCAR-8 and NCI/ADR-RES cell lines. We used these cell lines to decipher the mechanisms of ER as NCI/ADR-RES cells express higher activities of SOD, glutathione peroxidase and transferases than OVCAR-8 cells. We found that ER was equally cytotoxic to both cells; ER formed more ROS in OVCAR-8 cells than in NIH/ADR-RES cells. Ferrostatin-1, an inhibitor of ferroptosis, inhibited ER-induced cell death in both cell lines. In contrast, RSL3 (RAS-selective lethal 3), an inducer of ferroptosis, significantly enhanced cell death in both cell lines. ER induced significant lipid peroxidation only in OVCAR-8 cells. We found that RSL3 was more cytotoxic to NCI/ADR-RES cells and significantly enhanced ER-induced lipid peroxidation in both cells, indicating GPX4 was involved in the process of ER-mediated ferroptosis. ER treatment also differentially modulated several ferroptosis related genes (e.g., HMOX1/OH1, and CHAC1) in these cells, indicating ER-induced cell death may be mediated differently in OVCAR-8 and NCI/ADR-RES ovarian cells. Our studies suggest that combinations of ER and RSL3 may contribute significantly to the treatment of ovarian cancers, including those that are resistant to other therapeutic agents due to the presence of P-gp or tumors with Ras mutation in the clinic. ER induced ferroptosis may also be an important treatment modality for resistant tumors expressing MDR1 in the clinic.

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H₂O₂-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.

Classical Hodgkin lymphoma (cHL) is a highly curable disease (70-80%), even though long-term toxicities, drug resistance, and predicting clinical responses to therapy are major challenges in cHL treatment. To solve these problems, we characterized two cHL cell lines with acquired resistance to doxorubicin, KM-H2dx and HDLM-2dx (HRSdx), generated from KM-H2 and HDLM-2 cells, respectively. HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gem-citabine, brentuximab vedotin (BV), and γ-radiation. Both HDLM-2 and HDLM-2dx cells had an intrinsic resistance to BV but not to the drug MMAE. HDLM-2dx acquired cross-resistance to caelyx. HRSdx cells had in common: decreased CD71, CD80, CD54, cyt-ROS, HLA-DR, DDR1, CD44; increased Bcl-2, CD58, COX2, CD26, CCR5, invasive capability; increased CCL5, TARC, PGE2, TGF-β, and capability to hijack monocytes. In HRSdx cells, less sensitive to DNA damage and oxidative stress, the efflux drug transporters MDR1 and MRP1 were not up-regulated, and doxorubicin accumulated in cytoplasm rather than in nucleus. Both autophagy inhibitor chloroquine and extracellular vesicles (EVs) release inhibitor GW4869 enhanced doxorubicin activity and counteracted doxorubicin resistance. In conclusion, this study identifies common modulated antigens in HRSdx cells, the associated cross-resistance patterns, and new potential therapeutic options to enhance doxorubicin activity and overcome resistance.

Abstract Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to an efficient induction of anti-tumor immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins mimicking natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

The part transportation efficiency is a main factor of aircraft sortie generation rate. Part transportation is used to transport spare part from base to carrier. Transportation strategy depends on both demand on carrier and inventory in transportation base. The transportation time and stochastic demand will induce fluctuations of cost and inventory. Thus, a Takagi-Sugeno fuzzy system of dynamic part transportation is established considering transportation time and stochastic demand. And a novel Takagi-Sugeno fuzzy robust control is designed for dynamic part transportation, which will keep transportation cost and part inventory stable. First of all, a fuzzy model with stochastic demand and transportation time is proposed. Then, a novel robust control with cross rule groups is conducted according to production and transportation strategy, which will reduce fluctuations induced by strategies switch. Moreover, robust stability is guaranteed and part can be supplied in time under a low cost. Finally, simulation illustrates usefulness and quickness of the novel Takagi-Sugeno fuzzy robust control. Besides, the proposed method will be useful in other transportation electrification systems with delay time and uncertainty.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine).is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cells. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), in vitro. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n=3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

This article provides a systematic review of the crosslinking strategies used to produce microgel particles in microfluidic chips. Various ionic crosslinking methods for gelation of charged pol-ymers are discussed, including external gelation via crosslinkers dissolved or dispersed in the oil phase, internal gelation methods using crosslinkers added to the dispersed phase in their non-active forms, such as chelating agents, photo-acid generators, sparingly soluble or slowly hydrolyzing compounds, and methods involving competitive ligand exchange, rapid mixing of polymer and crosslinking streams, and merging polymer and crosslinker droplets. Covalent crosslinking methods using enzymatic oxidation of modified biopolymers, photo-polymerization of crosslinkable monomers or polymers, and thiol-ene “click” reactions are also discussed, as well as the methods based on sol-gel transitions of stimuli responsive polymers triggered by pH or temperature change. In addition to homogeneous microgel particles, the production of structurally heterogeneous particles such as composite hydrogel particles entrapping droplet interface bi-layers, core-shell particles, organoids, and Janus particles are also discussed. Microfluidics offers the ability to precisely tune chemical composition, size, shape, surface morphology, and internal structure of microgels by bringing in contact multiple fluid streams in a highly controlled fashion using versatile channel geometries and flow configurations and allowing controlled crosslinking.

Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses of bacteria which are known to affect growth rate. Here, we aim to disentangle how the interplay between resistance development and associated fitness costs is affected by stress responses. We performed de novo resistance evolution of wild-type strains and single-gene knockout strains in stress response pathways using four different antibiotics. Throughout resistance development, the increase in minimum inhibitory concentration (MIC) is accompanied by a gradual decrease in growth rate, most pronounced with amoxicillin or kanamycin. By measuring biomass yield on glucose and whole-genome sequences at intermediate and final timepoints, we identified two patterns of how the stress responses affect the correlation between MIC and growth rate. First, single-gene knockout E. coli strains associated with reactive oxygen species (ROS) acquire resistance faster and mutations related to antibiotic permeability and pumping out occur earlier. This increases the metabolic burden of resistant bacteria. Second, the ΔrelA knockout strain which has reduced (p)ppGpp synthesis, is restricted in its stringent response, leading to diminished growth rates. The ROS-related mutagenesis and the stringent response are vulnerabilities within the fitness of resistant strains that can possibly be targeted to prevent development of resistance.

We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

There have been a great number of investigations about the influence of weak magnetic fields on biological systems, such as isolated cells and whole organisms. This is also a subject of considerable medical concern since old epidemiologic observations have indicated a possible tumorigenic effect of these fields. Their mechanism of action, however, is not firmly established. A large number of biological effects of electromagnetic fields have been attributed either to the production of reactive oxygen species (ROS) or to the entrance Ca²⁺ in the cell. A new biochemical pathway is proposed that covers these two possibilities: the primary effect of the magnetic field would be by the mechanism of radical pairs resulting in the production of ROS; these could activate the ion channels TRPM2 producing cellular inflow of Ca²⁺, which would induce the calcium dependent effects. Thus, a large number of biological effects observed up to the present could be explained.

The potentially active A subunit of coagulation factor XIII (FXIII-A) is an intracellular transglutaminase expressed in various cell types including platelets and monocytes/macrophages. It is involved in stabilizing protein structures by cross-linking through Nε-(?-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque and are important in determining its structural/functional features. Two of their important functions are the accumulation of oxidized LDL in the lipid core, and by cross-linking structural proteins they may stabilize the plaque and protect the thrombi of atherogenic origin against fibrinolytic degradation. It is important to know whether these functions operate in parallel utilizing the same cellular compartments. First, we showed that monocyte-derived human macrophages significantly increase their FXIII-A content when up-taking oxidized LDL. This phenomenon is very likely independent of the process of transformation into foam cells, as the transformation of vascular smooth muscle cells into foam cells fails to result in the expression of FXIII-A. FXIII containing macrophage-like cells are abundant in the plaque and FXIII-A is also present in the extracellular core. Several cells co-stained for FXIII-A and for Oil Red O suggest that expression of FXIII-A and lipid up-take are common features of macrophages present in the atherosclerotic plaque.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

Knowledge of the biological effects of molecular hydrogen (H2), hydrogen gas, is constantly expanding giving a reason for optimism for several healthcare practitioners regarding management of multiple diseases, including socially significant ones. However, mechanisms underlying the biological effects of H2 are still being actively argued. In this review, we focus on mast cells as a potential target for H2 at the level of a specific tissue microenvironment. H2 regulates processing of pro-inflammatory components of the mast cell secretome and their entry into the extracellular matrix; this can significantly affect the state of the integrated-buffer metabolic environment and the structure of the immune landscape of the local tissue microenvironment. The analysis performed highlights several potential mechanisms for developing the biological effects of H2 and offers great opportunities for translating the obtained findings into clinical practice.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Unavoidable exposure to radiosensitive normal tissues around cancerous tumor during the radiotherapy can cause side effects such as self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Nevertheless, clinical use of currently available radiation protective agents is limited because of their generic cytotoxicity. A study on radiation protective effect of delphinidin was conducted with proton-beam-exposed human colon cells (CCD-18Co). The measurement in changes of survival fractions of CCD-18Co with/without delphinidin administration at different radiation doses were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The changes in expression of reactive oxygen species (ROS) and in activities of antioxidant enzymes were measured by colorimetric assays using pertinent assay kits. The measurement of pro-apoptosis/pro-survival protein expressions using Western blot assay and the measurement of DNA damage using comet assay were also fulfilled to evaluate the molecular level of radiation damages in CCD-18Co cells. The experimental results revealed that the pre-administration of delphinidin regulated antioxidant enzymes, reduced ROS, decreased DNA damage, regulated pro-apoptosis/pro-survival proteins, and eventually reduced apoptosis of CCD-18Co cells. In conclusion, it is claimed that delphinidin is nontoxic natural radiation protective compound, and thus delphinidin can be used to protect normal colon tissues during the proton beam therapy.

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain vascular tone vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, with a potential impact on cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. Reactive nitrogen species (RNS), particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone during high oxidative stress conditions. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, as well as to explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

The essence of cross-modal generation and retrieval modeling for image-text interactions lies in semantic consistency. Among these, cross-modal representation alignment serves as the foundational requirement for achieving cross-modal semantic consistency. The crux of our proposed method entails the collaborative training of an image captioning model(referred to as the ’captioner’) and a pair of contrastive encoders for image-text matching(referred to as the ’concoder’). This synergistic approach yields concurrent enhancements in concoder’s performance, captioner’s proficiency, and cross-modal semantic coherence. We coin the proposed method as ‘ReCap’. To begin, we initialize the concoder through knowledge distillation from a pre-trained model. During the training process, we use the output of the initialized concoder as input to a residual attention network, jointly training it with the captioner to achieve semantic consistency. Subsequently, we iteratively update the concoder during the image-text momentum encoding phase using the residual attention network, creating a closed-loop for semantic consistency resolution. Upon completion of training, the concoder and captioner modules can be used independently to perform tasks related to cross-modal retrieval and cross-modal generation of text and images. In order to substantiate the efficacy of our proposed method, we initially conducted empirical experiments encompassing image-text retrieval and image captioning tasks, employing a widely recognized benchmark dataset, MSCOCO. Subsequently, we assessed the fine-grained cross-modal alignment performance of the concoder through an image classification task on the iNaturalist 2018 dataset. The achieved performance metrics notably surpassed those achieved by several incumbent state-of-the-art models, thus validating the proficiency of our method. Finally, motivated by the practical requirements of handling the nature conservation image data, we performed caption annotation for the iNaturalist 2018 dataset. Subsequently, we trained the ReCap on this annotated data. Experimental results demonstrate that our proposed method can maintain semantic consistency between cross-modal retrieval and image caption generation for species with similar visual features but distinct semantics. This achievement signifies a meaningful exploration in the field of cross-modal semantic consistency representation, holding significant practical value in the domain of biological research.

The manufacture of SiC-based composites is quite widespread, and currently different methods are employed for to produce them. The most efficient method, taking into account the cost/performance ratio, is reactive melt infiltration. It consists in infiltrating liquid silicon into a porous preform that must contain carbon, so that SiC is produced during infiltration. This chemical reaction is, in fact, the driving force of the process. In the present work, the synthesis of two SiC-based composite materials with very different applications and microstructures has been studied and optimized. In both cases, materials have been obtained with suitable properties for the selected applications. One of the materials studied is SiCp/Si for protection systems such as armor jackets, and the other one is Cf/SiC for use in braking systems. For the optimization, the dwell time and the atmosphere (Ar or primary vacuum) were used as variables. It has been found that in both preforms the optimum conditions are 1 hour dwell time and a vacuum atmosphere at 1450 °C. The effect of these parameters on microstructure and infiltration kinetics are discussed.

To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

Reactive oxygen species and reactive nitrogen species in semen are both essential for fertilization process; however, they become harmful at excessive levels, causing oxidative stress and nitrosative stress, respectively. Recently, oxidation–reduction potential (ORP) has been used as a marker for measuring oxidative stress, and this study investigated the possibility of comprehensively evaluating nitrosative stress. The correlation between standardized ORP (sORP) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) and NOx per unit sperm was tested. Based on the previously reported cutoff value, samples were classified into oxidative stress-positive and negative groups. Thereafter, a receiver operating characteristic curve was drawn on 8-OHdG and NOx, and each optimal cutoff value was determined. Both standardized 8-OHdG and NOx significantly correlated with sORP. Although both correlated significantly with sORP in the oxidative stress group, no correlation was found in the nonoxidative stress group. The optimal standardized 8-OHdG level to determine oxidative stress status was 0.52 ng/106 spermatozoa, and the standardized NOx was 0.17 µM/106 spermatozoa/mL. The ORP is a simpler and quicker assay that can comprehensively assess oxidative and nitrosative stresses. Optimal cutoff values for both stresses were established in this study.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

SiC is a material with excellent mechanical and thermal properties, but with a high production cost. Obtaining SiC by reactive infiltration is an attractive method and at a much lower cost than the traditional sintering process. However, the reactive infiltration process presents a serious problem, which is the high residual silicon content, which decreases its range of application. The replacement of silicon with silicides is a widely used alternative. The present investigation shows the good mechanical properties of the SiC/IrSi₃ composite material obtained by reactive infiltration of SiC/C preforms with Ir-Si alloys. The thermomechanical analysis shows a high compatibility of silicide with SiC. The presence of the silicide shows a substantial improvement against the oxidation of the SiC/Si composites.

This paper updates earlier thoughts by the author on a putative propulsion system. The concept was based around static electromagnetic momentum, as expounded in the “Feynman Disk” and experimentally verified by Graham and Lahoz. That said, naïve static electromagnetic momentum schemes to achieve linear translation are defeated by “hidden momentum” mechanisms, so too are simple arrangements just cycling the fields; we shall survey the flaws in their arguments. It may however be possible to achieve linear translation by means of arrangements of torques with a novel mechanism to break the symmetry of forces (or torques) on the second half of the cycle as the field is switched off. At the time of earlier presentation no mechanism could be found to explain the momentum balance for the process but it was believed that momentum was being given to the zero-point of the field. We show that it is possible to dump angular momentum and thence linear momentum to the ground state by standard quantum analysis of the EM field. None of this violates the conservation of momenergy.

Immune disorders, characterized by dysregulation at cellular and inflammatory levels, result from a complex interplay of genetics and environmental factors that lead to an abnormal immune response against autoantigens, triggering tissue damage. Recent research highlights reactive antibodies as key players in autoimmune diseases and graft rejection, but the complexity of their determination limits their use in clinic. Hence, we studied the specific binding profile of serological antibodies against a panel of cellular membranes in order to determine whether this antigenic panel could be used to diagnose specific immune disorders in humans. For this purpose, cell membrane microarrays of spleen, liver, and kidney tissues of monkey, rat, and human were developed, and human sera were analyzed, including healthy controls, patients with autoimmune disorders, and kidney transplant patients. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and Human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in the serum of patients as potential biomarkers of immune disorders.

Schizophrenia is a spectrum of neuropsychiatric deformities, characterized by hallucination, delusion, mood disorders, speech pathology, and neurocognitive deficits. Among various clinical manifestations, hallucination has been recognized as a core psychotic symptom that occurs more frequently in schizophrenia. A significant number of subjects with neurocognitive disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other neurological diseases like stroke and epileptic seizure also experience hallucinations. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the specific cellular mechanism contributing to hallucinations remains ambiguous. Neurodegeneration in the hippocampus of the brain has been identified as a predominant pathogenic determinant of dementia. While the scientific proof for the neurodegeneration in schizophrenia is limited, the occurrence of dementia in schizophrenia has become increasingly evident. To note, both neurodegenerative, neurodevelopmental, and neuropsychiatric disorders display impaired neurogenesis in the brain. Impaired neurogenesis in the hippocampus has been linked to dementia and mood disorders. Notably, the early phase of many neurodegenerative disorders has been characterized by reactive neuroblostosis and aberrant cell cycle activation in mature neurons leading to the fluctuation in neurogenic processes leading to abnormal synaptogenesis and neurotransmission in the brain. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Activity of the Nox1 centered NADPH oxidase complex depends on the activator NoxA1 and the organizer NoxO1. NoxO1 itself is not involved in electron transfer for superoxide formation. Instead, by creating proximity of all components in the right place NoxO1 enables a constitutive formation of reactive oxygen species by that complex. All subunits should form the complex in a 1:1:1 ratio. When analyzing different cell lines in this study, we found an unequal expression of the component on mRNA level with an excess of NoxO1. Even with plasmid-based overexpression of individual components of Nox1 centered NADPH oxidase complex results in different expression of their mRNA, with NoxO1 mRNA being best expressed. Despite an unchanged high level of NoxO1 mRNA over a wide range of transfected plasmid, protein expression is increased with accelerating plasmid concentrations. We thought to analyze the ability of NoxO1 to induce ROS formation, when present in different ratio to Nox1 and NoxA1. To this end, we used Hek293 cells with constitutive expression of Nox1 and NoxA1 transfected with increasing concentrations of NoxO1. Our results suggest that ROS formation by the Nox1 centered NADPH oxidase strongly depends on the level of NoxO1 and a surplus of NoxO1 further increases the activity of the complex.

Sputtered reactive multilayers applied as a heat source in electronic joining processes are an emerging technology. Their use promises low-stress assembly of components while improving the thermal contact and reducing the thermal resistance. Nanostructured surface modifications can significantly enhance adhesion and reliability of joints between different materials. This work examines reactive multilayer of nickel and aluminum, directly sputtered on nanostructured black silicon surfaces and compares their phase transformation with reference samples deposited on pristine silicon surface. The investigation of the quenched self-propagating reaction reveals a clear influence of the nanostructured surface on the prolongation of the phase transition. Rapid thermal annealing tests result in the formation of Al_1.1Ni_0.9 phase. The nanostructured interface seems to hinder the full transformation of the parent material. The surface modification improves the adhesion of the formed alloy on silicon surfaces and can possibly increase the reliability of joints based on reactive aluminum/nickel multilayer. The use of black silicon, a nanostructured surface modification, is thus a promising approach to realize reliable multi-material joints in complex systems.

In this work, two plasmonic structures with two different periodic nanostructures (nanodisk and nanostrip arrays) separated from the gold layer by an ultrathin dielectric Al2O3 layer are proposed, and their optical properties are simulated as 3-dimensional models using COMSOL Multiphysics software tool. The optical responses, such as the amplification of the electric field and the scattering, absorption and extinction cross sections of the two structures, are investigated and compared. The results show that both structures show strong field enhancement in their gap layer, and the structure with the periodic array of metal nanodisks shows stronger field enhancement and larger absorption, extinction, and scattering cross sections in its dipole resonance wavelength, which is defined as a bright plasmonic mode. In addition, some weaker resonant modes are observed for both structures and the reason for their generation is dis-cussed. The analysis of different possible modes in such structures is crucial for their application in various fields.

Abstract Background Fatigue Syndrome (FS) is described as extreme exhaustion following ordinary activities. Sleep deprivation, the use of antidepressants, autoimmune illnesses, and anemia are also risk factors for FS. Symptoms of FS include headache, dizziness, and dyspnea, among others. Objective: This study focused on assessing the prevalence of fatigue syndrome (FS) and its association with depression and anxiety, among the medical students in Saudi Arabia. Methodology In this cross-sectional investigation conducted in 2023, 740 medical students participated. Data were gathered using an online survey, which encompassed four key sections: Sociodemographic details, the 11-item Chalder Fatigue Questionnaire (CFQ), the 9-item Primary Health Questionnaire (PHQ) assessing depression, and the Generalized Anxiety Disorder 7-item (GAD-7) scale. Analyses were performed by the use of SPSS version 25. Results A total of 740 students were surveyed, 417 (56.4%) satisfied the diagnostic requirements for fatigue syndrome (FS), with most of them being females. Furthermore, 234 (31.2%) and 296 (40.8%) of the participants reported having significant anxiety symptoms and depressive symptoms, respectively. FS was positively correlated with symptoms of anxiety and depression (P

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

Photoacoustic imaging is attracting a great deal of interest owing to its distinct advantages over other imaging techniques such as fluorescence or magnetic resonance image. Availability of photoacoustic probes for reactive oxygen and nitrogen species (ROS/RNS) could shed light on a plethora of biological processes mediated by these key intermediates. Tetramethylbenzidine (TMB) is a non-toxic and non-mutagenic colorless dye that develops a distinctive blue color upon oxidation. In this work we have investigated the potential of TMB as photoacoustic probe for ROS/RNS. Our results indicate that TMB reacts with hypochlorite, hydrogen peroxide, singlet oxygen and nitrogen dioxide to produce the blue oxidation product, while ROS such as the superoxide radical anion, sodium peroxide, hydroxyl radical or peroxynitrite yield a colorless oxidation product. TMB does not penetrate Escherichia coli cytoplasm but is capable of detecting singlet oxygen generated in its outer membrane.

Cross-cultural mobility is a phenomenon that is increasingly growing, and the resulting stress has become a severe health issue. Thus, we conducted a systematic review of articles reporting research on stress measures of cross-cultural mobility or acculturative stress, emphasizing its internal structure. We adopted the PRISMA procedures for scoping reviews (e.g., searching articles in databases), resulting in the inclusion 20 articles in the final analysis that present evidence of validity based on the internal structure of 16 measures. The most common factors identified were related to cultural stressors, language stressors, and discrimination stressors. After analyzing a cross-cultural mobility stress concept implicit in the definitions used in the articles, we found that most measures of acculturative stress did not evaluate it according to the Stress and Coping Model of Lazarus and Folkman. Most measures only focused on part of the phenomena (some estimated the stressors, others the coping strategies). Few took into account the physiological and psychological responses to internal or external stressors, and even fewer considered its positive aspects (eustress). Consequently, it is pivotal to develop measures that take into account the multiple dimensions of the cross-cultural mobility stress. Other results (e.g., validity evidence of the measures) and limitations of this systematic scoping review are presented and discussed.

Many medicinal plants and their essential oils are used to treat or prevent diseases without the risk of mutagenicity, carcinogenicity, or teratogenicity. Eucalyptus essential oils are commonly used as preservatives, flavoring agents, and in various consumer goods. Eucalyptus leaves are being widely studied due to their volatile essential oils, including 1,8-cineole, p-cymene, α and β-pinene, limonene, citronellal, citral, eudesmol, terpinen-4-ol, terpineol, α–phellanderene, and 9β-sitosterol. Among these compounds, 1,8-cineole is the most abundant. Eucalyptus leaves are rich in flavonoids and phenolic compounds and are thus a great source of antioxidants. 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays are used to measure antioxidant capacity. The antioxidant activity of Eucalyptus essential oil is stronger than that of standard antibiotics like Erythromycin, Cefixime, and Gentamicin due to the presence of significant terpenoids in addition to phenolic chemicals and flavonoids. The lower the IC₅₀ value, the higher the antioxidant potential. Phenolic compounds and flavonoids are often associated with beneficial health outcomes, including anti-inflammatory and antioxidant effects, anti-cancer properties, reduced risk of cardiovascular diseases, prevention of age-related neurodegenerative diseases, and prevention of Alzheimer’s disease. Flavonoids also play an essential role in plants, including protecting against reduction, fertility, reproduction, and infection. Due to their anti-inflammatory, anti-oxidative, and immune-modulatory properties, flavonoids are crucial for pharmacological, medical, and nutraceutical applications.

Polymers' controlled pyrolysis is an economical and environmentally friendly solution to prepare activated carbon. However, due to the experimental difficulty in measuring the dependence between tissues and pyrolysis parameters at high temperatures, the unknown pyrolysis mechanism hinders access to the target products with desirable morphologies and performances. In this study, we investigate the pyrolysis process of polystyrene under different heating rates and temperatures employing reactive molecular dynamics (ReaxFF-MD) simulations. A clear profile of the generation of pyrolysis products determined by the temperature and heating rate is constructed. It is found that the heating rate affects the type and amount of pyrolysis intermediates and their timing, and low-rate heating helps yield more diverse pyrolysis intermediates. While the temperature affects the pyrolytic tissues of the final equilibrium products, either too low or too high a target temperature is detrimental to generating large areas of graphitized tissue. The established theoretical evolution process matches experiments well, thus contributing to preparing target activated carbons by referring to the regulatory mechanism of pyrolytic tissues.

From oxidative eustress and distress, to bioenergetic metabolism, and cell death, the reactive species interactome (RSI) and mitochondria are two connected metabolisms that require further investigation improving redox medicine. The step before, finding new clues needs a comprehensive discussion of the two metabolisms, and their relationship. Here, the review focuses on the RSI-mitochondria axis, from mitochondrial roles to crosstalk between mitochondria and other organelles, and the major implication of the RSI in mitochondrial roles. Specifically, the review discussed the apoptosis-necroptosis-ferroptosis death traingle, mitochondrial protein quality control system, calcium homeostasis, and mitochondrial metabolome. Through mitochondrial diseases, and mitochondrial dysfunction associated with diseases, the RSI-mitochondria axis is proposed as a brand-new perspective, including with the involvement of bacterial microbiota, on redox signaling, and redox medicine.

Each year, the global population and agriculture suffer critical agricultural output losses as a result of severe drought devastation. Physiological drought occurs when plants are unable to extract water from the soil, even though it is available in the root zone. Apart from having a significant effect on plant physiology, drought stress has the effect of reducing crop yield. Drought stress influences plant metabolism both directly and indirectly. Drought stress alters the morpho-anatomical, physiological, and biochemical composition of plants, thereby decreasing transpiration water loss and increasing the efficiency with which plants use their water. Constant water loss through transpiration, combined with previously lost water, results in leaf water deficits. Nonetheless, drought stress has a wide variety of effects, ranging from lesions to confusion. Plant health is harmed when their ability to absorb water and nutrients, interact with their environment, and breathe is harmed. Apart from oxidative damage to plants, it may also result in cell death, which can occur under certain conditions when cells are exposed to their environment. Drought induces a plethora of physiological and molecular changes in plants, the majority of which assist them in adapting to the harsh environment. To mitigate drought's adverse effects, we must first gain a better understanding of how drought affects plant physiology. The purpose of this research is to better understand how drought affects plant development by examining the causes and effects of drought stress.

Future, flexible thermal energy conversion systems require new, demand-optimized high-performance materials. The High performance Ferritic (HiperFer) stainless steels, under development at the Institute of Microstructure and Properties of Materials (IEK-2) at Forschungszentrum Jülich GmbH in Germany, provide a balanced combination of fatigue, creep and corrosion resistance at reasonable price. This paper outlines the scientific background of alloy performance development, which resulted in an age-hardening ferritic, stainless steel grade. Furthermore, technological properties are addressed and the potential concerning application is estimated by benchmarking versus conventional state of the art materials.

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

Texture has long been considered an important attribute for food acceptance. However, which specific textural characteristics contribute to overall acceptance of a food is not well understood. It has been suggested that texture contrasts and combinations are a universal feature in giving foods a desirable texture, yet this notion is largely based upon anecdotal data. This study uses multiple survey research methods to assess the importance of texture contrast and combinations across cultures (Poland, U.S.A., and Singapore). Participants (n = 288) completed a survey that included overt measures of food texture contrast importance as well as free response questions regarding texture. The overall importance of texture for food liking was not different across the populations. However, the participants from Singapore and Poland gave more importance to a desirable food having multiple textures than the U.S.A. cohort. When looking at free responses, participants were twice as likely to mention combinations (multiple textures) with a texture contrast when describing foods they liked, in comparison to foods they disliked. This was observed across all 3 cultures. However, the type and quantity of texture terms used within combinations were different among cultures. For instance, Asians enjoyed more texturally diverse food combinations than the other two cultures. These findings highlight the importance of texture contrasts and combinations in three distinct cultures.

This paper presents a novel CNN-based architecture, referred to as Q-Net, to learn local feature descriptors that are useful for matching image patches from two different spectral bands. Given correctly matched and non-matching cross-spectral image pairs, a quadruplet network is trained to map input image patches to a common Euclidean space, regardless of the input spectral band. Our approach is inspired by the recent success of triplet networks in the visible spectrum, but adapted for cross-spectral scenarios, where for each matching pair there are always two possible non-matching patches; one for each spectrum. Experimental evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed approach improves the state-of-the-art. Moreover, the proposed technique can also be used in mono-spectral settings, obtaining a similar performance to triplet network descriptors, but requiring less training data.

Chaotic theory is commonly being researched for application in image encryption scheme (IES). In this paper, a novel two-dimensional cross hyperchaotic Sine-modulation-Logistic map (2D-CHSLM) based on the famous Sine and Logistic maps. The hyperchaotic behaviors of 2D-CHSLM is testified with the help of their bifurcation diagrams, trajectory plots, Lyapunov exponents, sample entropy, C0 complexity, permutation entropy and 0-1 test. A new bit-level IES with traditional encryption structure is proposed utilizing 2D-CHSLM. The 2D-CHSLM-IES performs a 2D-CHSLM-based bit-level confusion using zig-zag transform and a 2D-CHSLM-based cross coupled diffusion operations for generating a highly secure cipher-image. Then the simulations and security analyses are further carried out with the help of key space, key sensitivity, histogram, correlation, information entropy, differential attack, noise and data loss attacks, prove that the security of the proposed 2D-CHSLM-IES

Since the introduction of Cross-laminated Timber (CLT) in Austria in the early 1990s, the adoption of this 90°-crosswise-laminated product has seen exponential growth worldwide. Compared to traditional laminated timber products (e.g. glulam), CLT provides improved dimensional stability, but with reduced out-of-plane bending stiffness. To improve the bending stiffness, while maintaining relative dimensional stability, a modified orientation of the inner layers in a diagonal direction can be used. This novel product is Diagonal-Cross-laminated Timber (DCLT), a composite timber product, consisting of inner layers which are rotated at different angle-ply orientations between 0 and 90 degrees to the outer layers. To properly model the out-of-plane bending behavior of the DCLT, analytical models and Finite Element Analysis (FEA) were used and the results were validated by third-point bending tests performed on DCLT panels with angle-ply orientations of 10°, 20°, 40°, 70°, and a conventional CLT 90° panel. The results indicate that DCLT panels with angle-ply cross-layers have a structural advantage in out-of-plane bending over traditional CLT (90°) panels. The development of DCLT and its introduction to the industry could enable the use of lower-quality timber that would not otherwise satisfy structural requirements for CLT.

In cross-country skiing the time difference between a race winner and the person coming second is typically very small. Since much of the energy is spent on overcoming resistive forces, a relatively small reduction of these can have a significant impact on the results. The resistive forces come partly from the friction in the tribological interface, between the ski and the snow, and as with many tribological applications the characterisation of its origin, plays an important role in determining the frictional properties. Also in cross-country ski friction, there are several scales impacting the frictional performance, with the major contributors being the ski-camber profile and ski-base structure. Macro-scale measurements of the ski's camber profile under load, are often used to determine how adequate the ski is for a specific condition. The characteristic properties usually obtained are, the force required to collapse the ski to a certain camber height, the topography of the kick-wax zone, and by simple means a determined lengths of the frictional interface, i.e., the apparent contact length. To this date, there are some mathematical models, but there is no robust way of determining the macro-scale contact properties between a cross-country ski and a counter surface using simulations. In the present paper an Artificial neural networks (ANN) is trained to predict the ski-camber profile for various loads placed at different positions, and a well established deterministic approach is used to simulate the contact between the ANN-predicted ski-camber profile and a linearly elastic body with a flat surface, representing the snow. The results suggest that this method is feasible for the determination of the apparent contact characteristics of different skis. Moreover, we show that the apparent contact area does not linearly depend on the load, and that the elastic properties of the counter surface also has a large impact on the apparent contact area and the average apparent contact pressure.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify three main factors that play a crucial role in the physiopathology of NAFLD: oxidative stress, insulin resistance, and the key role of carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.

In this work, oligoesters with terminal hydroxyl groups were obtained by directed glycolytic degradation of polyethylene terephthalate. The possibility of obtaining bifunctional reactive oligomers with an average molecular weight of 865 g mol-1 by directed glycolytic destruction via a dissolution-degradation strategy in dimethyl sulfoxide at a low concentration of ethylene glycol (32.3 mass parts per 100 mass parts of polyethylene terephthalate) was shown. This process allows us to partially solve the urgent problem of recycling post-consumer polyethylene terephthalate.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyse the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week during 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week during 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

Background and Objective: Although whole body-electromyostimulation (WB-EMS) has been shown to favorably improve body composition in several research studies, it has not been confirmed how it affects adipose tissue-derived biomarkers and circumferences of the abdomen and thighs. Materials and Methods: Twenty participants of obese elderly women were randomly classified into an EMS group (EMSG; n = 10) or a non-EMS group (CON; n = 10). The WB-EMS suits used in this study enabled the simultaneous activation of 8 muscle groups with selectable intensities for each phase. Stimulation frequency was selected at 85 Hz, impulse-width at 350 μ seconds, and impulse-rise as a rectangular application. Impulse duration was 6 seconds with a 4-second break between impulses. The EMS sessions were combined with aerobic dancing 3 times a week for 12 weeks. Both groups received the same program; however, the CON did not receive electrical stimuli. Biomarkers and body composition including circumferences of the abdomen and thighs were measured on Week 0 and Week 12. Results: Compared with the CON, 1) a significant effect of the EMS-intervention concerning decreased body weight (p = 0.032) and increased basal metabolic rate (p = 0.029) were evident. The thigh subcutaneous fat and total fat of EMSG were not significantly changed, but those of CON were significantly increased after 12 weeks. 2) The biomarkers of CON either increased or showed no change, although the interleukin (IL)-6 was significantly (p = 0.028) decreased in EMSG. Specifically, C-reactive protein (CRP; p = 0.005) and alpha-fetoprotein (p = 0.050) of CON were significantly increased after 12 weeks. In addition, the IL-6 (p = 0.034), CRP (p = 0.001), carcinoembryonic antigen (p = 0.017), and low density lipoprotein (p = 0.005) of EMSG were lower than those of CON in the end of experiment. 3) Conclusions: The results indicate that EMS intervention improved body composition and reduced negative biomarkers, thus highlighting its effectiveness.

Magnesium hydroxide continuous coagulation process was used for treating simulated reactive orange wastewater in this study. Effects of mixing conditions and retention time on the coagulation performance and floc properties of magnesium hydroxide were based on the floc size distribution (FSD), zeta potential and floc morphology analysis. Floc formation and growth in different reactors were also discussed.The results showed that increasing rapid mixing speed led to a decrease in the final floc size. Floc formation process was mainly carried out in rapid mixer, rapid mixing speed of 300rpm was chosen according to zeta potential and removal efficiency. Reducing retention time caused relatively small floc size in all reactors. When influent flow is 30 L/h (retention time of 2min in rapid mixer), the average floc size reached 8.06μm in rapid mixer, through breakage and re-growth, the floc size remained stable in flocculation basin. After growth, the final floc size reached to 11.21μm in sedimentation tank. The removal efficiency of reactive orange is 89% in magnesium hydroxide coagulation process.

Nowadays a recognized need for accurate observations of atmospheric aerosols (AEs) and reactive gases (RGs) exists in the framework of regional, national and global near-surface networks based on permanent or mobile measurement stations. In this context, a paramount and not-trivial issue is related to the correct execution of continuous sampling of ambient air and its subsequent distribution to measurement analyzers hosted inside the stations. Sampling artifacts must be minimized for obtaining reliable pictures of ambient air composition. To respond to this need, a suite of novel “smart” and relatively low-cost systems for the continuous sampling of ambient air was developed in the framework of the Project I-AMICA (2012 – 2015, www.i-amica.eu). These systems were designed to execute AE and RG measurements according with WMO/GAW and ACTRIS recommendations and standard operation procedures. A particular attention was dedicated to the stabilization and control of the sampling flow rates and temperatures. The analysis of one full year of operations at the WMO/GAW regional station of Capo Granitola (GAW ID: CGR, Italy), allowed to conclude that these systems are effective in meeting the technical requirements for correct execution of AE and RG measurements

Photodynamic inactivation (PDI) combines the nontoxic photosensitizer (PS) and visible light to generate reactive oxygen species (ROS), which can cause oxidative damages in (on) microbial organisms. Previously, we have shown that chitosan can augment the bactericidal efficacy mediated by PDI against bacteria and Candida. In this study, we showed that the antimicrobial action of chitosan to augment PDI relates to the enlargement of cell surface destruction. The microbial cell surfaces exhibit severe irregular shapes after PDI in the presence of chitosan. Furthermore, increase in the concentrations or incubation time of chitosan significantly reduce the amounts of photosensitizers TBO required, indicating that chitosan could be a synergistic agent with PDI against human pathogens. A prolonged lag phase was found in PDI surviving microbial cells, in which chitosan can act to synergistically eradicate the cells. Once the impaired cells rebuild their cellular functions from PDI-induced damage, the increased cytotoxic effect of chitosan disappeared. Together, our results suggest that chitosan with an augmented bactericidal activity after PDI is to inhibit the rehabilitation of PDI surviving cells, leading to microbial death.

We formulate a more straightforward, symmetry-based techniques in manually computing the determinant of any n×n matrix by revisiting Dodgson’s condensation method and strategically applying elementary row operations and the definition and properties of determinants. The result yields a more simplified mnemonical algorithm than the usual reduction by elementary row operations and co-factor expansion and with minimal terminal divisions performed compared to Dodgson’s internal divisions.

This article presents the results of a cross-disciplinary applied study exploring investors’ protections in the context of distributed ledger technology (DLT) smart contracts. Fusing legal, business, and technical perspectives, we developed a framework for protection from non-commercial risks for stablecoins, taking advantage of DLT and AI. A key concept we propose is the monitoring of disinformation and fake news to prevent malicious parties from abusing our solution. Based on the similarities between central bank digital currencies (CBDCs) and stablecoins, we propose scaling up our results to all future internet investments performed without face-to-face contact between the investor and the company.

The danger is still very large from cross site scripting attacks. When designing web applications We must follow as much as we can prevention rules and don’t leave any loophole to our programs. Experience is a great factor for programmers to know these attacks and for a trainee programmer is a difficult task to spot all the weak points. In this article we present a tutorial on launching an XSS attack and also we propose simple solutions.

Sentinel-1 (S1) extra-wide (EW) swath data in cross-polarization (horizontal-vertical, HV or vertical-horizontal, VH) are strongly affected by the scalloping effect and thermal noise, particularly over areas with weak backscattered signals, such as sea surfaces. Although noise vectors in both the azimuth and range directions are provided in the standard S1 EW data for subtraction, the residual thermal noise still significantly affects sea ice detection by the EW data. In this paper, we improve the denoising method developed in previous studies to remove the additive noise for the S1 EW data in cross-polarization. Furthermore, we propose a new method for eliminating the residual noise (i.e. multiplicative noise) at the sub-swath boundaries of the EW data, which cannot be well processed by simply subtracting the reconstructed 2-D noise field. The proposed method of removing both the additive and multiplicative noise was applied to EW HV-polarized images processed using different Instrument Processing Facility (IPF) versions. The results suggest that the proposed algorithm significantly improves the quality of EW HV-polarized images under various sea ice conditions and sea states in marginal ice zone (MIZ) of the Arctic. This is of great support for the utilization of cross-polarization SAR images in wide swaths for intensive sea ice monitoring in polar regions.

Chikungunya virus (CHIKV) is an alphavirus that causes febrile illness punctuated by severe polyarthralgia. After the emergence of CHIKV in the Western Hemisphere, multiple reports of congenital infections were published that documented neurological complications, cardiac defects, respiratory distress, and miscarriage. The Western Hemisphere is endemic to several alphaviruses and whether antigenic cross-reactivity can impact the course of infection has not been explored. Recent advances in biomedical engineering have produced cell co-culture models that replicate the cellular interface at the maternal fetal axis. We employed a trans-well assay to determine if cross-reactive antibodies affected the movement and replication of CHIKV across placental cells and into an embryoid body. The data show that antibodies to Venezuelan equine encephalitis virus (VEEV) significantly reduced CHIKV viral load in embryoid bodies. The data highlight that viral pathogenesis can be cell-specific and that exploiting antigenic cross-reactivity could be an avenue for reducing the impact of congenital CHIKV infections.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

In recent years, magnetic fields have emerged as a non-thermophysical treatment with a signifi-cant impact on microbial fermentation processes. Brassica trispora is a microorganism known for its indus-trial-scale production of lycopene and high yield of single cells. This study aimed to in-vestigate the impact of low frequency magnetic fields on lycopene synthesis by Brassica trispora and elucidate the underlying mechanism for enhancing lycopene yield. The results indicated that both the intensity and duration of the magnetic field treatment influenced the cell. Exposing the cell to a 0.5 mT magnetic field for 48 hours on the second day of fermentation resulted in a lyco-pene yield of 1473.16 mg/L, representing a re-markable increase of 216.1% compared to the con-trol group. Transcriptome analysis revealed that al-ternating magnetic field significantly up-regulated genes related to ROS and cell membrane structure, leading to a substantial increase in lycopene production. Scanning electron microscopy revealed that the magnetic field treatment resulted in rough, loose, wrinkled surface morphology of the mycelium, along with a few mi-cropores, thereby altering the cell membrane permeability to some extent. Moreover, there was a significant increase in intracellular ROS content, cell membrane permeability, key enzyme activi-ty involved in lycopene metabolism, and ROS-related enzyme activity. In conclusion, the alter-nating fre-quency magnetic field can activate a self-protective mechanism that enhances lyco-pene synthesis by modulating intracellular ROS content and cell membrane structure. These find-ings not only deepen our understanding of the impact of magnetic fields on microbial growth and metabolism but also provide valuable insights for developing innovative approaches to en-hance carotenoid fermentation.

Broomrape (Orobanche cumana), root parasitic weed, negatively affects sunflower, thereby causing severe yield losses and required controls on O. cumana infestation. Brassinosteroids (BRs) plays key roles in plant growth and provides resilience to weed infection. This designed study evaluated the mechanisms by which BRs ameliorates O. cumana infection in sunflower (Helianthus annuus). The pretreatment of sunflower seeds with various concentrations of BRs (1, 10, and 100 nM) were applied with and without O. cumana infestation. Under O. cumana infection, a significant reduction in plant height (38.61%), fresh/dry biomass, photosynthesis and regulation in plant defense (POX, GST), BRs signaling (BAK1, BSK1 to BSK4) and synthesis (BRI1, BR6OX2) associated genes. Moreover, O. cumana elevated the levels of MDA, OH‒, H2O2 and O2•‒ in leaves/roots by 77%/112%, 62%/104%, 57%/98% and 55%/89.4% and caused ultrastructural damages in leaves/roots, suggesting the severe oxidative or cellular damages in sunflower. In response, plants activate activities of SOD and POD enzymes as well as reduced or oxidized glutathione, but unable to stimulate APX and CAT activities. Addition of BRs, especially at 10 nM notably lowered the production of oxidative stress, activated the enzymatic and non-enzymatic antioxidants. The downregulation in the reported genes by BRs attributed to the increased resilience of sunflower (via susceptible reaction). In nutshell, the pretreatment of BRs enhanced the sunflower resistance to O. cumana infection by improving the planta growth and biomass, photosynthesis, activating the antioxidant defense system, lowering the oxidative stress, cellular damages and modulating the expression of BR synthesis and signaling genes.

Osteoporosis, often linked to increased osteoclast activity due to menopause or aging, was the focus. In this study, the inhibitory effects of Salicornia europaea L. (SE) water extract of desalted SE (WSE) were investigated on osteoclast differentiation and bone loss in ovariectomized mice. The findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as evidenced by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. Gene expressions related to osteoclast differentiation, including NFATc1, TRAP, cathepsin K, and DC-STAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoyl quinic acids (DCQAs) and saponins in WSE were detected, with 3,4-, 3,5-, and 4,5-DCQA isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQA, as preventive or therapeutic agents against osteoporosis and related conditions.

The article concerns problems related to the assessment of reactive power in power networks with non-linear, fast-varying loads, such as electric arc furnaces, rolling mill drives, etc. The operation of this type of loads is characterized by the introduction of interharmonic currents (including higher harmonics) into the power supply network and a relatively low power factor. Rapid changes in the RMS value of the current also cause voltage fluctuations and the related phenomenon - flicker. Therefore, there is a need to evaluate the selection of power of compensating devices taking into account the random nature of load changes and the distortion of current and voltage waveforms, in particular interharmonic components, the impact of which has not been fully investigated so far. To analyze the random nature of load changes, autocorrelation functions were used, which allowed for the estimation of the expected values of the arc furnace current distortion coefficient (based on the recorded waveforms). In order to determine the parameters of reactive power compensating devices, and in particular capacitor banks, an autocorrelation function in the exponential-cosine-sine form was used, which meets the conditions of differentiation. The article contains comparative results of calculations of the reactive power of capacitor banks determined using different methods.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, impaired epidermal barrier function and unbalanced inflammatory response. The pathophysiology involves immune dysregulation, with a predominance of T-helper 2 cells. AD is triggered by many known and unknown factors, including oxidative stress. Reactive oxygen species (ROS) contribute to AD pathogenesis by causing cellular damage and inflammation. Moreover, increased oxidative stress in AD leads to hyperactivation of the MAP kinase pathway, extracellular signal-regulated kinase (ERK) and p38, with DNA damage and subsequent skin barrier dysfunction. This narrative review provides a comprehensive overview of the role of natural antioxidant compounds, highlighting their potential therapeutic value in AD management. They include vitamin D, vitamin E, pyridoxine (vitamin B6), Vitamin C, carotenoids and melatonin, in AD. Despite some studies have shown an association between vitamin D, vitamin E, vitamin C and carotenoids levels and AD course, conflicting results exist. Pyridoxine supplementation has shown mixed results, and melatonin has demonstrated antioxidant and anti-inflammatory properties in AD; in fact, melatonin treatment resulted in a decrease in symptoms in patients with AD, although no significant correlation with changes in sleep latency was reported. In addition, iron and zinc (Zn) supplementation can also improve AD symptoms. Further research is needed to elucidate the optimal use of these natural antioxidants in AD treatment

Salinity stress affect plant growth and development by causing osmotic stress, and nutrient imbalances through excess Na+, K+ and Cl- ion accumulations that induce toxic effects during germination, seedling development, vegetative growth, flowering, and fruit set. However, the effects of salt stress on such processes, especially in polyploidised leguminous plants remains unexplored and scantly reported compared to their diploid counterparts. This paper discusses the physiological and molecular response of legumes towards salinity stress based osmotic and ionic imbalances in plant cells. A multigenic response involving various compatible solutes, osmolytes, ROS, polyamines and antioxidant activity, together with genes encoding proteins involved in the signal transduction, regulation and response mechanisms to this stress were identified and discussed. This discussion reaffirms polyploidisation as the driving force in plant evolution and adaptation to environmental stress constraints such as drought, feverish temperatures, and in particular, salt stress. As a result, thorough physiological and molecular elucidation of the role of gene duplication through induced autopolyploidisation and possible mechanisms regulating salinity stress tolerance in grain legumes must be further studied.

We determined the optimal composition of reactive magnetron sputtered TiO2-SnO2 mixed layers for electrochromic purposes. We determined and mapped the composition and optical parameters by Spectroscopic Ellipsometry (SE). The Ti‐ and Sn‐ targets have been placed separately, and the Si-wafers on glass substrate (30 cm× 30 cm) were moved under the two separated targets (Ti and Sn) in Ar‐O2 plasma. Different (Effective Medium Approximation (EMA) and oscillator-type) op-tical models were used to obtain the composition maps and thickness of the sample layer. Scanning Electron Microscopy (SEM) with Energy-Dispersive X-ray Spectroscopy (EDS) has been used to check the SE results. The ’goodness’ of diverse optical models have been compared, according to the conditions of sample preparation. We show that in the case of molecular-level mixed layers 2‐Tauc‐Lorentz oscillator model is better than the Bruggeman Effective Medium Approximation (BEMA). The electrochromic properties of mixed metal oxides that deposited by reactive sputtering have been mapped, too.

Cold stress is a major environmental factor affecting the growth, development, and productivity of various crop species. With the current trajectory of global climate change, low temperatures are becoming more frequent and can significantly decrease crop yield. Wheat (Triticum aestivum L.) is the first crop to be domesticated and is the most popular cereal crop in the world. Due to a lack of systematic research on cold response pathways and gene regulatory networks, the underlying molecular mechanisms of cold signal transduction in wheat are poorly understood. This study reviews recent progress in wheat, including the ICE-CBF-COR signaling pathway in cold stress and the effects of cold stress on hormonal pathways, reactive oxygen species (ROS), and epigenetic regulation. This review also highlights outstanding issues that are crucial for understanding the interactions between wheat and low-temperature conditions.

Familial colorectal cancer (CRC) is only partially explained by known germline predisposing genes. We performed whole genome sequencing in 15 Polish families of many affected individuals, without mutations in known CRC predisposing genes. We focused on loss-of-function variants and functionally characterized them. We identified a frameshift variant in the CYBA gene (c.246delC) in one family and a splice site variant in the TRPM4 gene (c.25-1 G>T) in another family. While both variants were absent or extremely rare in gene variant databases, we identified four additional Polish familial CRC cases and two healthy elderly individuals with the CYBA variant (odds ratio 2.46, 95% confidence interval 0.48-12.69). Both variants led to a premature stop codon and to a truncated protein. Functional characterization of the variants showed that knockdown of CYBA or TRPM4 depressed generation of reactive oxygen species (ROS) in LS174T and HT-29 cell lines. Knockdown of TRPM4 resulted in decreased MUC2 protein production. CYBA encodes a component in the NADPH oxidase system which generates ROS and controls, e.g., bacterial colonization in the gut. Germline CYBA variants are associated with early onset inflammatory bowel disease, supported with experimental evidence on loss of intestinal mucus barrier function due to ROS deficiency. TRPM4 encodes a calcium-activated ion channel, which in a human colonic cancer cell line controls calcium-mediated secretion of MUC2, a major component of intestinal mucus barrier. We suggest that the gene defects in CYBA and TRPM4 mechanistically involve intestinal barrier integrity through ROS and mucus biology, which converges in chronic bowel inflammation.

(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance is a target for new therapies. The purpose of this review is to identify the compounds with antioxidant properties that have been tested for wound healing and to summarize the available evidence on their effects. (2) Methods: A literature search was conducted and included any study that evaluated the effects or mechanisms of antioxidants in the healing process (in vitro, animal models, or human studies). (3) Results: Seven compounds with antioxidant activity were identified (Curcumin, N-acetyl cysteine, Chitosan, Gallic Acid, Edaravone, Crocin, Safranal, and Quercetin) and 46 studies reporting the effects on the healing process of these antioxidants compounds were included. (4) Conclusions: These results highlight that numerous novel investigations are being conducted to develop more efficient systems for wound healing activity. The application of antioxidants is useful against oxidative damage and accelerates wound healing. Designing biomaterials that can scavenge excess reactive oxygen species requires new technologies and further research, especially human studies.

In recent years, electrochemical methods utilizing reactive electrochemical membranes (REM) have been recognized as the most promising technologies for the removal of organic pollutants from water. In this paper, we propose a 1D convection-diffusion-reaction model concerning the transport and oxidation of oxalic acid (OA) and oxygen evolution in the flow-through electrochemical oxidation system with REM. It allows the determination of unknown parameters of the system by treatment of experimental data and predicts the behavior of the electrolysis setup. There is a good agreement in calculated and experimental data at different transmembrane pressures and initial concentrations of OA. The model provides an understanding of the processes occurring in the system and gives the concentration, current density, potential and overpotential distributions in REM. The dispersion coefficient was determined as a fitting parameter and it is in good agreement with literary data for similar REMs. It is shown, that the oxygen evolution reaction plays an important role in the process even under the kinetic limit, and its contribution decreases with increasing total organic carbon flux through the REM.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

Soil pH, either low (acidity) or high (alkalinity) is one of the major constraints that affect many biochemical and biological processes within the cell. The present study was carried out to understand the oxidative damage and antioxidant defense in wheat (Triticum aestivum L. cv. BARI Gom-25) grown under different pH regimes. Eight-day-old seedlings were exposed to growing media with different pH levels (4.0, 5.5, 7.0 and 8.5). Seedlings grown in pH 4.0 and in pH 8.5 showed reductions in biomass, water, and chlorophyll contents; whereas plants grown at pH 7.0 (neutral) exhibited better performance. Extremely acidic (pH 4.0) and/or strongly alkaline (pH 8.5)-stress also increased oxidative damages in wheat by excess reactive oxygen species (ROS) generation and methylglyoxal (MG) production, which increased lipid peroxidation and disrupted the redox state. In contrary, the lowest oxidative damage was observed at neutral condition followed by strong acidic condition (pH 5.5), which was attributed mainly due to better performance of the antioxidant defense and glyoxalase systems. Interestingly, seedlings grown at pH 5.5 showed a significant increase in morphophysiological attributes compared with extreme acidic (pH 4.0)- and strong alkaline (pH 8.5)-stress treatments, which indicates the tolerance of wheat to the acidic condition.

Reactive energetic plasticizers (REPs) coupled with hydroxy-telechelic poly(glycidyl azide-co-tetrahydrofuran) (PGT)-based energetic polyurethane (PU) binders for use in solid propellants and plastic-bonded explosives (PBXs) were investigated. The generation of gem-dinitro REPs along with a terminal alkyne stemmed from a series of finely designed approaches to not only satisfy the common demands as conventional energetic plasticizers but prevent the migration of plasticizers. The miscibility and rheological behavior of a binary mixture of PGT/REP with various REP fractions were quantitatively determined by differential scanning calorimetry (DSC) and rheometer, respectively, highlighting the promising performance of REPs in the formulation process. The kinetics on the distinct reactivity of propargyl vs. 3-butynyl species of REPs towards the azide group of the PGT prepolymer in terms of Cu-free azide-alkyne 1,3-dipolar cycloaddition (1,3-DPCA) was studied by monitoring 1H nuclear magnetic resonance spectroscopy and analyzing the activation energies (Ea) obtained using DSC. The thermal stability of the finally cured energetic binders with the incorporation of REPs indicated that the thermal stability of the REP/PGT-based PUs was maintained independently of the REP content. The tensile strength and modulus of the PUs increased with increasing the REP content. In addition, the energetic performance and sensitivity of REP and REP triazole species was predicted.

Recent advancements in machine learning have ushered in innovative techniques for augmenting datasets, particularly through contrastive learning in the computer vision domain. This study pioneers the application of contrastive learning for sentiment analysis, introducing a novel approach termed EmoConLearn. By fine-tuning contrastive learning embeddings, EmoConLearn significantly surpasses BERT-based embeddings in sentiment analysis accuracy, as evidenced by our evaluations on the DynaSent dataset. This research further delves into the efficacy of EmoConLearn across various domain-specific datasets, highlighting its versatility. Additionally, we investigate upsampling strategies to mitigate class imbalance, further enhancing EmoConLearn's performance in sentiment analysis benchmarks.

Background: Given the extensive translation of the Prolapse Quality of Life Questionnaire (P-QoL) into many languages, it is imperative to develop an Arabic version to facilitate study on Pelvic organ health within the Arabian culture. Objective: To investigate, cross culturally adapt and validate Arabic version of the P-QoL. Study Design: Cross-cultural adaptation and psychometric testing. Methods: A total of 90 participants were included in the study. This cross-sectional study went through two phases; during phase I, the P-QoL was translated and adapted from English into Arabic. The Arabic version was psychometrically validated during phase II using the test-retest reliability internal consistency with Cronbach’s alpha coefficient, convergent construct validity (CC) among the four study tools using Spearman’s coefficient (r) and discriminative validity using Mann-Whitney test to find differences between the means of the two samples. Results: A satisfactory level of semantic, conceptual, idiomatic, and content comparability was reached in the cross-cultural adaptation of the Arabic version of the P-QoL questionnaire. The internal consistency was high in terms of psychometric validation, with a Cronbach’s alpha coefficient of 0.971 for the P-QoL questionnaire. The test-retest results showed a high reliability with interclass correlation coefficient (ICC) of P-QoL = 0.987. The convergent construct validity was highly accepted (moderately strong), reflecting a positive correlation between the Arabic version of the P-QoL and the Australian Pelvic Floor Dysfunction Questionnaire (APFD) r = 0.68 (p &lt; 0.001). Similarly, a significant convergent validity of P-QoL Arabic version and Visual Analogue Scale (VAS) r = 0.47 (p &lt; 0.001) was found, as well as the correlation between the APFD and the VAS r = 0.46 (p &lt; 0.001). However, there were no significant correlation between the SF-12, the P-QoL, the APFD, and the VAS. Conclusion: Based on a significant correlation between the Arabic APFD and the VAS, the results reveal good reliability, internal consistency, and construct validity. It is recommended that Arabic-speaking females with pelvic organ prolapse use the Arabic version of the P-QoL. More research is needed to assess the responsiveness of the P-QoL.

Background: Abdominal wall hernias are a common condition that is seen in daily general surgery patients. However, still more researches are needed to be conducted regarding hernias. The aim of this study is to see the prevalence of hernias among patients admitted to the Department of Surgery of a tertiary care center. Methods: A descriptive cross-sectional study was performed among patients who admitted to the department of surgery in a tertiary care center between 1 August 2023 and 20 September 2023. All patients data were extracted to an excel sheet. Results: We had 760 patients who visited in this period. Only 272 patients (27.9 %) were diagnosed with hernias. We found 52.6 % of patients were male and 47.4 % of patients were female. The age between 46- 60 years old was the most to have hernias (97 patients). Inguinal hernias were the common among other types. Diabetes mellitus, hypertension, COPD, and hydrocele were found in 10.7 % of all patients. Conclusion: The prevalence of hernias in this study was nearly to other studies that conducted in the same conditions. Early diagnosis and patient’s education are the corner stone to prevent morbidities and mortalities.

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.

This research has critically argued that a vigilant combination of flexibility and certainty in spatial planning can bring about the most optimum planning outcomes. Therefore, to reproachfully evaluate the core argument, this research has tried to empirically respond to the research question of which balance of government intervention and market freedom produces the optimal economic, social and spatial outcomes. This research question has been further translated into an associated central hypothesis i.e., a hybrid planning system with an optimal balance between discretionary and regulatory planning approach can bring about the desired economic, social, and spatial outcomes.

Registry and survey data gave an opportunity to compare possible roles of social attitudes and social values in control and limit the COVID-19 pandemic. We analysed social values and time series of daily R0 (reproduction rate) estimates for 27 European countries. Embedded and affective autonomy are significantly negatively associated (p-Value<0.05) with controlled R0. It could mean that well interconnected societies with high attention to maximize utilities are more likely to couple with COVID-19. Hierarchy is significantly positively associated (p-Value<0.05) with controlled R0. Thus, hierarchical structures could inhibits control of COVID-19. The results emphasize the need to pay more attention to social values context in evaluating the effectiveness of mitigation strategies internationally.

There is tremendous interest, in the economic literature, for the determinants of firms’ capital structure decisions. A rich body of empirical works now exists that purports to identify firm- and country-level factors affecting firms’ financing patterns. In addition, more recently, a new stream of studies has emerged that investigates cross-regional variation in small firms’ capital structure. While small firms’ leverage does seem to vary across regions, at least in countries where significant regional differences in economic and financial development and in the quality of institutions exist, not much yet is known about variation in debt maturity, in debt in relation to equity, and between different types of small firms. The present paper aims to fill this gap through an empirical analysis of cross-regional variation in the capital structure of a sample of about 30,000 Italian small firms over a 13-year period, including the aftermath of the credit crunch that followed the 2007-8 global financial crisis. The findings confirm the view that small firms in underdeveloped regions are more financially constrained, but also amend some of the results shown in the literature, in particular by showing how small firms in Italy’s Southern regions have higher levels of equity and fixed assets than small firms in other regions.

In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate of panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed, and synthesized imidazolium RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including Oxygen Radical Absorbance Capacity, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging, Ferric Ion Reducing Antioxidant Power, Hydroxyl Radical Scavenging, and HA Fragmentation Assay. All results proved that imidazolium RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazolium RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Background: Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coro-nary heart disease. We investigated the relationship of CRP with findings from myocardial per-fusion imaging (MPI). Methods: In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) that underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6mg/L) within 1 month from MPI, were included. Patients had no infection or recent acute coronary syndrome. Results: the median CRP level was 4mg/L (2,10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (P = 0.006) and summed rest score (SRS) (P = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, P = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (P = 0.027 and P = 0.005 respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). Conclusion: A high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

Reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) manifest in individuals facing attachment system chal-lenges, particularly observed in minors under protective measures. The lack of standardized tools for assessing these difficulties and uncertainty about the most effective instruments from a psychometric perspective prompted this study. Using the COSMIN checklist, we systematically reviewed instruments assessing RAD, adhering to PRISMA and COSMIN guidelines. Examined tools included the Disturbance Attachment Inter-view, Preschool Age Psychiatric Assessment, Relationship Patterns Questionnaire, Assessment of RAD and DSED, Development and Well-Being Assessment, and Reactive Attachment Disorder Question-naire. Of the 11 articles analyzed, results highlight a research emphasis on internal consistency, structural and construct validity, sidelining other properties. While the instruments demonstrate strong structural validity, excellent internal consistency, and generally satisfactory error measurement results, the study concludes a dearth of investigations into psychometric properties for children and adolescents under protective measures.

Febrile infections are a common cause of presentation to the emergency department (ED) in chil-dren. While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; the better understanding of immunochemical pathways has nowadays led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models combining them for serious bacterial infections (SBI) diagnosis in febrile children. Litera-ture analysis showed that inflammatory response is a complex mechanism in which many bio-chemical and immunological factors contribute to host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined and for this reason it is reasonable to take them both into consideration in the evaluation of a febrile children. The potential of machine learning tools, who represent a real novelty in medical practice, in conjunction with routine clinical and biological in-formation, may improve accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pe-diatric precision medicine still uncertain. More data from further researches are needed to improve clinical practice and decision making using these new technologies.

Background: Polycystic ovary syndrome is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing polycystic ovary syndrome and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M, a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to polycystic ovary syndrome pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the polycystic ovary syndrome (n = 32) or the control group (n = 32). Blood samples were obtained between the third and fifth days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin, estradiol, homeostasis model assessment of insulin resistance and oncostatin M were analyzed. Results: Oncostatin M levels were significantly lower, but C-reactive protein levels were substantially higher in the polycystic ovary syndrome group than in the control group (p = 0.002, p = 0.001, respectively). Oncostatin M was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = -0.329, p =0 .017; ρ = -0.386, p = 0.005; ρ = -0.440, p = 0.001; ρ = -0.316, p = 0.023, respectively). Conversely, there was no correlation between oncostatin M and total testosterone level (ρ = 0.220; p = 0.118). In the context of inflammation and metabolic parameters, oncostatin M was inversely correlated with C-reactive protein, homeostatic model assessment for insulin resistance score, and low-density lipoprotein cholesterol (ρ = -0.353, p = 0.019; ρ = -0.275, p = 0.048; ρ = -0.470, p &lt; 0.001, respectively). The diagnostic performance of oncostatin M, C-reactive protein, homeostasis model assessment of insulin resistance, and non-high-density lipoprotein cholesterol for polycystic ovary syndrome is as follows: Oncostatin M, sensitivity: 50%, specificity: 75%, Accuracy: 63%, p = 0.009; C-reactive protein, sensitivity: 84%, specificity: 61%, Accuracy: 74%, p = 0.004; homeostasis model assessment of insulin resistance, sensitivity: 72%, specificity: 81%, Accuracy: 77%, p &lt; 0.001; and non-high-density lipoprotein cholesterol; sensitivity: 72%, specificity: 75%, accuracy: 73%, p &lt; 0.001. Conclusions: Plasma oncostatin M levels were considerably lower in patients with polycystic ovary syndrome than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of polycystic ovary syndrome. Thus, oncostatin M may be a novel therapeutic target for polycystic ovary syndrome and its metabolic complications.

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

Psilocybin-containing mushrooms, commonly known as magic mushrooms have antidepressant effect, however, their safety in cardiovascular diseases such as heart failure is not fully known and needs to be investigated. Cardiac hypertrophy is an independent risk factor for heart failure morbidity and mortality. Angiotensin II (Ang-II) plays a major role in the pathogenesis of cardiac hypertrophy. We investigated the cardiovascular safety of extracts of Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, and Psilocybe cubensis leucistic A+ strain mushrooms, well-known psilocybin-containing mushrooms in the Panaeolus and Psilocybe genus on Ang II-induced hypertrophy oxidative stress. The four mushrooms were grown, dried and extracted with 70% ethanol, cold and hot water. Extracts were tested for cytotoxicity on H9C2 cardiomyoblast cells. The cardiomyocytes were induced with (10 µM) AngII and treated with the three extracts of the four mushrooms over 48 hours. Control cells were serum starved but neither AngII induced nor treated while AngII cells were serum starved and stimulated with AngII but not treated. Losartan, an inhibitor of AngII type 1 receptor was used as positive control. Effects of the extracts on actin-filament labelling and cell surface area, mitochondrial activity, reactive oxygen species (ROS) and atrial natriuretic peptide levels were determined. Stimulation with AngII lowered cell viability, increased the cell width measurements and intracellular ROS levels significantly compared to control cells. The results indicated that the ethanol and water extracts of the four psilocybin mushrooms did not exacerbate the angiotensin II-induced hypertrophy conditions, but the extracts had cardio-protective activity against angiotensin II-induced oxidative stress. The phytochemical analysis of the extracts confirmed detections of known compounds with antioxidant and anti-inflammatory effects in the water and ethanol extracts of these four psilocybin mushrooms.