Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

(1) Background: AI technology has been deeply applied to online shopping platform to provide more accurate and personalized services for consumers. It is of great significance to study the different functional experience of AI for consumers to improve the current application status of AI technology.(2)Method: Based on the "S-O-R" model, this study divided the AI technology expe-rienced by the consumers of online shopping platform into accuracy, insight and interaction experience. Takes the perceived value as the mediating variable from the prospect of perceived utility value and perceived hedonic value. This article use empirical research method to analyze the effect of three dimensions of online shopping AI experience to research the internal influence mechanism of consumers purchase intention. (3) Results:① The accuracy, insight and interaction experience of AI marketing technology have a significant positive impact on consumers' per-ceived utility value and hedonic value respectively; ②Both of the perceived utility value and perceived hedonic value obtained by AI technology experience can promote the formation of consumers' purchase intention; ③ The perceived hedonic value was better than perceived utility value to promote the consumers' purchase intention; ④The results of multi group analysis show that some younger and less experiences consumers groups prefer the pleasure experience such as shopping desire stimulation, shopping process relaxation and pleasure that AI marketing brought. However, utilitarian value cannot promote this kind of consumers' purchase intention. (4) Con-clusions: Perceived utility value and perceived hedonic value can be the intermediary between AI technology and consumers' purchase intention.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

Exploring the dynamic behavior of cellular metabolism requires a standard laboratory method that guarantees rapid sampling and extraction of the cellular content. We propose a versatile sampling technique applicable to cells with different cell wall and cell membrane properties. The technique is based on irreversible electroporation with simultaneous quenching and extraction by using a microfluidic device. By application of electric pulses in the millisecond range, permanent lethal pores are formed in the cell membrane of Escherichia coli and Saccharomyces cerevisiae, facilitating the release of the cellular contents; here demonstrated by the measurement of glucose-6-phosphate and the activity of the enzyme glucose-6-phosphate dehydrogenase. The successful application of this device was demonstrated by pulsed electric field treatment in a flow-through configuration of the microfluidic chip in combination with sampling, inactivation, and extraction of the intracellular content in a few seconds. Minimum electric field strengths of 10 kV/cm for E. coli and 7.5 kV/cm for yeast S. cerevisiae were required for successful cell lysis. The results are discussed in the context of applications in industrial biotechnology, where metabolomics analyses are important.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

For the set of probability measures ${\sf I}(X)$, where $X$ is a compact Hausdorff space, we propose a new way to introduce the topology by using open subsets of the space $X$. Then, among other things, we give a new proof that for a compact Hausdorff space $X$ the space ${\sf I}(X)$ is also a compact Hausdorff space. For a Tychonoff space $X$, we consider the topological space ${\sf I_{\tau}}(X)$ of $\tau$-smooth idempotent probability measures on $X$,and show that the space ${\sf I_{\tau}}(X)$ is \v{C}ech-complete if and only if the given space $X$ is \v{C}ech-complete.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

Background: We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Methods: Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured by gelatin zymography, fluorometric assay, and immunohistochemistry. Results: APC accelerated wound healing in WT mice, but had negligible effect in PAR-2 KO mice. APC stimulated murine cutaneous wound healing was associated with differential 0temporal production of MMP-2 and MMP-9, with the latter peaking on Day 1 and the former on Day 6. In-hibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity 25~50, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. Conclusion: This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR2.

A hydrothermal technique with microwave heating (200 °C, 2 hours, 2 magnetrons, 2.45 GHz) was modified to obtain UV-C luminescent LaPO4: Pr3+ colloidal nanorods for the potential use in X-ray cancer theranostics. For further possible biofunctionalization, a compound of tartaric acid formed under basic conditions was used as a coating and stabilizing agent to provide colloidal properties to the surface of nanoparticles in basic to neutral aqueous media, which was confirmed by zeta potential measurements. In addition, the colloidal properties and clustering processes of synthesized LaPO4:Pr3+ nanorods in aqueous solutions with different pH values were studied in real time using a highly sensitive laser ultramicroscope operating according to the “light-sheet” scheme. A comparative analysis of the transmission electron microscopy, X-ray powder diffraction and high-energy spectroscopy showed the different effects of synthesis parameters on the morphological, crystalline and luminescent properties of the obtained nanorods. Through optimization of the synthesis parameters, stable aqueous solutions of m-LaPO4:Pr3+ nanorods with sizes less than 30 nm and an intensity of UV-C luminescence equal to 5-10% of the unmodified nanofibers were obtained.

Background and Aims: The impact of antibody response after direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association of changes in anti-HCV antibody titers after pre-LT DAA therapy with allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (DAA-naïve group). Higher incidence of post-LT BCs was observed in the DAA group (P = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (P = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (P < 0.005). Conclusion: In conclusion, we speculated that anti-HCV antibody titer upregulation, which might have been induced by restoration of HCV-specific immune responses with pre-LT DAA therapy, were associated with post-LT allograft injury.

Estrogens play a protective role during early life stages. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression in low-grade inflammatory conditions like established atherosclerosis. Our single-center cohort study assessed sex-specific associations of gonadal hormones with oxidative stress, inflammation, and myocardial injury markers in 111 patients (37% women) diagnosed with acute myocardial infarction (MI) between July 2011 and December 2013. Blood samples were collected within 48 hours of symptom onset, and we measured sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitive C-reactive protein (CRP), white blood cell counts (WBC), and cardiac enzymes (creatine kinase [CK], the CK Muscle-Brain fraction [CK-MB], and high-sensitive troponin T [hsTnT]). The SYNTAX score gauged coronary disease severity from coronary angiography results. In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels (OR 1.011, p=0.047 - CK; OR 1.018, p=0.013 - CK- MB; OR 1.019, p=0.005 - TnT), peak WBC count (OR 1.487, p=0.015 - CK ; OR 1,709, p=0,005 - CK- MB; OR 1.391, p=0.012 - TnT), and peak CRP plasma levels (OR 1.040, p=0.033 - CK; OR 1.024, p=0.029 - CK-MB; OR 1.063, p=0.006 - TnT). T levels and E2/T ratio were associated with post-PCI CRP in these men (OR 0.980, p = 0.024 - T, OR 1.010, p = 0.076 - CRP). For women, peak WBC was a marker of highest testosterone (OR 1.348, p = 0.062), and only WBC was a significant indicator of myocardial injury extent (OR 1.426, p=0.039 - CK; OR 1.384, p=0.036 - CK-MB; OR 1.299, p=0.048 - TnT). During acute MI, elevated endogenous estradiol levels correlate with myocardial necrosis severity in men, while in women, increased leukocyte levels indicate acute myocardial damage. Elevated plasma T is associated with increased WBC in women. In men, post-PCI plasma CRP specifically indicates endogenous T levels and E2/T ratio during the acute phase.

The visual appearance of humans derives significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly in the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). Localization of a second ‘immature’ SOX10 negative melanocyte population, which was c-KIT/MITF double positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. These studies describe an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells destined to synthesize mela-nin ultimately or could they contribute to the hair follicle in non-melanogenic ways.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

In the Czech Republic, the Universal Soil Loss Equation provides the basis for defining the soil protection strategy. Field rainfall simulators were used to define the actual cover-management factor values of the most extensively seeded crops in the Czech Republic. More than 380 simulations between 2016 and 2021 provided data. The methodology focused on multi-seasonal measurements to cover the most important phenological phases. A comparison with the original USDA values for maize showed that it is desirable to redefine the C-factor. 71 fallow plot experiments showed that the rainfall-runoff relation is much easier to replicate than the actual sediment transport. For 30-minute intensive rainfall, the runoff ratio reached 62%, and the coefficient of variation was 25%. On saturated soil, the runoff ratio reached 81% and the coefficient of variation dropped to 12%. Soil protection techniques have a significant effect on runoff reduction. Maize seeded after cover crops and combined with reduced tillage or direct seeding can reduce the runoff ratio to 10-20% for ‘dry’ conditions and to 12-40% for ‘saturated’ conditions. Concerning soil loss, the variations are greater, with the coefficient of variation reaching 42% during fallow plot experiments. The reader should consider associated uncertainties.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

This paper investigates whether currency risk is priced differently in the different sectors (industrial, financial, and basic materials) of equity markets in a sample of developed United States of America (USA) and developing economies (Brazil, India, Poland, and South Africa). The paper makes use of the following techniques: (i) Univariate Autoregressive Fractionally Integrated Moving Average and Exponential General Autoregressive Conditional Heteroskedastic (ARFIMA-EGARCH), (ii) the Markov-Switching method (MS), and (iii) the Canonical Vine Copulas (C-Vine) techniques. Using a sample of daily data made of the foreign exchange rate against the domestic currency and equity market sectors; our findings show that there is an asymmetry effect between equities markets and the foreign exchange rate: there is a heterogeneous, strong, and positive dependence between the two. Higher equities prices are associated with depreciation of local currencies, according to US dollar (USD) exchange rates. In addition, we find that the selected emerging economies are pricing a positive and considerable currency risk. The pricing of currency risk has a varied effect in both regimes representing the states of the economy. In fact, when currency risk pricing has a beneficial impact on certain sectors of the economy, investors predict better returns.

Quadruplex-interactive small molecules have a wide potential application, not only as drugs but also as sensors of quadruplexes structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4. Insertion of a positive charge upon methylation of quinoline/isoquinoline nitrogen increases compounds capacity to selectively stabilize G4s compared to duplex DNA, with a preference for parallel structures. Among these, compounds having a relative 1,3-position between the charged methylquinolinium/isoquinolinium nitrogen and the amide linker are the best G4 stabilizers. More interestingly, these ligands showed different capacities to selectively block DNA polymer-ization in a PCR-stop assay and to induce G4 conformation switches of hybrid h-Telo G4. Mo-lecular dynamic simulations with the parallel k-RAS G4 structure showed that the relative spatial orientation of the two methylated quinoline/isoquinoline rings determines the ligands mode and strength of binding to G4s.

Aegilops columnaris Zhuk. is tetraploid grass species (2n=4x=28, UcUcXcXc) closely related to Ae. neglecta and growing in Western Asia and a western part of the Fertile Crescent. Genetic diversity of Ae. columnaris was assessed using C-banding, FISH, nuclear and chloroplast (cp)DNA analyses, and gliadin electrophoresis. Cytogenetically Ae. columnaris was subdivided into two groups, C-I and C-II, showing different karyotype structure, C-banding and FISH patterns. Group C-I was more similar to Ae. neglecta. All types of markers revealed significant heterogeneity of the C-II group, although group C-I was also polymorphic. Two chromosomal groups were consistent with plastogroups identified in a current study based on sequencing of three chloroplast intergenic spacer regions. The similarity of group C-I of Ae. columnaris with Ae. neglecta and their distinctness from C-II indicate that divergence of the C-I group was associated with minor genome modifications. Group C-II could emerge from C-I relatively recently, probably due to introgression from another Aegilops species followed by a reorganization of the parental genomes. Most C-II accessions were collected from the very narrow geographic region, and they might originate from a common ancestor. We suggest that the C-II group is at the initial stage of species divergence and undergoing an extensive speciation process.

Plants are affected by soil environments to the same extent they affect soil functioning through interactions between environmental and genetic factors. Here, five plant species (broad bean, pea, cabbage, fennel, and olive) grown under controlled pot conditions were tested for their ability to differently stimulate the degradation of standard litter. Litter, soil C and N contents and soil microbial abundance were measured. The architecture and morphological traits of roots systems were also evaluated by using specific open-source software (SmartRoot). Soil chemical and microbiological characteristics were significantly influenced by the plant species. Variations in soil C/N dynamics were correlated with the diversity of root traits among species. Early-stage decomposition of the standard litter changed on the basis of the plant species. The results indicated that key soil processes are governed by interactions between plant roots, soil C and N, and the microbial metabolism that stimulate decomposition reactions. This, in turn, can have marked effects on soil chemical and microbiological fertility, both fundamental for sustaining crops, and can promote the development of new approaches for optimizing soil C and N cycling, managing nutrient transport, and sustaining and improving net primary production.

The non-structural protein NS3/4A protease is a critical factor for hepatitis C virus (HCV) maturation that requires activation by NS4A. Synthetic peptide mutants of NS4A were found to inhibit NS3 function. The bridging from peptide inhibitors to heterocyclic peptidomimetics of NS4A has not been in consideration in literature, and therefore, we decided to explore this strategy to develop a new class of NS3 inhibitors. In this report, a structure-based design approach was used to convert the bound form of NS4A into 1H-imidazole-2,5-dicarboxamide derivatives as first generation peptidomimetics. This scaffold mimics the buried amino acid sequence Ile-25` to Arg-28` at the core of NS4A21`-33` needed to activate the NS3 protease. Some of the synthesized MOC compounds were able to compete with and displace NS4A21`-33` for binding to NS3. For instance, N5-(4-guanidinobutyl)-N2-(n-hexyl)-1H-imidazole-2,5-dicarboxamide (MOC-24) inhibited the binding of NS4A21`-33` with a competition IC50 of 1.9 ± 0.12 µM in a fluorescence anisotropy assay, stabilized the denaturation of NS3 by increasing the aggregation temperature by ΔTagg 0.6 ± 0.140 ℃. MOC-24 also inhibited NS3 protease activity in a fluorometric assay. Molecular dynamics simulations rationalized the structure-activity relationship (SAR) differences between the active MOC-24 and the inactive MOC-26. Our data shows that MOC compounds are possibly the first examples of NS4A peptidomimetics that demonstrated promising activities against NS3 proteins.

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of T. cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF) and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 is less stimulated in CF than CM and L6E9. After T. cruzi infection, localized FN disorganization was observed in infected CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.

Various types of electroconductive additives were evaluated for high C-rate capability in an attempt to extend practical application of high-areal-capacity lithium–sulfur batteries that employ an aluminum-foam current collector. Carbon nanofibers (CNFs) were found to be the most effective additive, with the ability to attain a high-sulfur-loading of 40 mg cm−2. A CNF-containing cell exhibited gravimetric capacities of 1094 and 758 mAh gsulfur−1 (46.8 and 32.4 mAh cm−2) at 0.05 and 0.1 C-rate, respectively, in an ether-based electrolyte. Because a CNF-containing slurry exhibits low viscosity even at a high solid ratio, it could be filled into the aluminum foam. Additionally, a lithium–sulfur battery with high-sulfur-loading had an energy density of ~120 Wh kg−1, a value that was calculated from the weight of the components of the cathode, anode, current collectors, electrolyte, and separator. Assuming that the amount of electrolyte decreases and that the energy density of cells accumulate, a theoretical energy density of 522 Wh kg−1 was estimated. Moreover, it was found that even if a high-areal-capacity was achieved, the discharge capacity converged at a high C-rate, unless there was an improvement in ion diffusion in the bulk electrolyte. This is considered a limitation of sulfur cathodes with high-sulfur-loading.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

The pleiotropic biochemical and antioxidant functions of Vitamin C (Vit C) have recently sparked interest in its application in intensive care. Vit C protects important organ systems such as the cardiovascular, neurologic and renal system during inflammation and oxidative stress. Vit C also influences the systems of coagulation and inflammation and its application might prevent the development of organ damage. The current evidence of Vit C’s effect on the pathophysiological reactions during various acute stress events, such as sepsis, shock, trauma, burn and ischemia-reperfusion injury imposes the question, if the application of Vit C might be especially beneficial for cardiac surgery patients, who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of Vit C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between Vit C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence regarding the administration of Vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage and most the appropriate application strategy.

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson’s disease (PD), but many unmet needs and gaps remain. Device based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies but there are concerns due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps with stimulation of the vestibular brainstem sensory network which extensively innervates brain regions regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

A significantly reduced stress concentration effect and a stable deformation behavior are exhibited by the arc-like S-shaped auxetic structure. Analytical works beyond the bar and hinge method to capture structural effects, such as bending, shearing, etc., in the S-structure are scarce in the literature. The deformation pattern of the S-structure is dominated by bending and shearing within the linear elastic region. In this work, Timoshenko beam theory is used to derive closed-form expressions for overall elastic modulus and Poisson’s ratio. This agrees well with the results of finite element simulations. An adjusted R-square value of over 0.99 and almost 0.82 is obtained for elastic modulus and Poisson’s ratio, respectively. From parametric studies, it’s established that under quasi-static transverse load, strut thickness and the angle `α’ are the most important parameters for controlling elastic modulus, specific energy absorption, negative Poisson’s ratio (NPR) effect, and relative density of the entire auxetic structure. Also, it’s found that energy absorption and elastic modulus increase together. Interestingly, the elastic modulus of the structure under transverse load lies in the range from 3 MPa to 250 MPa, which means this structure is compliant enough and can be used in cushioning, packaging, soft robotics applications, etc.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

The future index prices are viewed as a critical issue for any trader and investor. For this craving, various models have shown up in the literature. The Geometric Brownian motion (GBM) is one of the popular models. This work examines four types of GBM as per the presence of memory or kind of volatility. These models include classical GBM with memoryless and constant volatility assumptions, SVGBM with memoryless and stochastic volatility assumption, GFBM with memory and constant volatility assumption, and SVGFBM with memory and stochastic volatility assumption. These models are utilized in an empirical study to forecast the future index price of Energy Sector in the Saudi Stock Exchange Market. The assessment was led by utilizing two error standards, mean square error (MSE) and mean absolute percentage error (MAPE). The outcomes showed that the SVGFBM occupies the highest level of accuracy according to smallest values of MSE and MAPE. While the accuracy of GBM come in the tail of the list models under study. These results have affirmed the positive affection of combining memory and stochastic volatility assumption into the GBM model, which agreed findings of numerous earlier works. Furthermore, the findings showed the GFBM models are more accurate than GBM models regardless of the type of volatility. While, under the same type of memory, the models with stochastic volatility assumption are more accurate than the corresponding models of constant volatility assumption. In general, all models considered in this work uncovered high accuracy through the value of MAPE ≤ 10%. This indicates of the ability of applying these models in a real financial environment. Through this empirical study, we can say that the Energy Sector in Saudi Arabia is predictable and stable and afterward we urge financial investors and stockholder to trade and invest in this sector.

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles compared to previously reported protocols.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally, and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Methods: Using droplet digital polymerase chain reaction (ddPCR) we comprehensively analyzed and distinguished ccfDNA and ccf mtDNA in the serum and CSF of PD and control patients. Results: The quantitative analysis of serum ccf-DNA in PD patients demonstrated significant increase of ccf mtDNA and ccfDNA compared to healthy control patients and significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients compared to healthy controls. These decreases were not statistically significant, but were in agreement with previous data. In-terestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. Limitations: the small sample size of serum and CSF were the main limitations of this study. Conclusion: To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR and indicating the distribution of the copy number of ccf mtDNA, as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater than ccfDNA potential to lead the development of novel treatments for PD patients.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

In the southeastern coast of Brazil, the bays of Ilha Grande and Sepetiba are linked by the Ilha Grande Channel, where remarkably vigorous currents have been consistently observed. The sheer intensity of these currents defies a simple explanation through tidal forcing alone, prompting researchers to delve into potential influences such as basin resonance and the baroclinic effect. This study aims to elucidate the role of remote meteorological effects within this complex hydrodynamic system. A numerical approach with a coastal model nested within an ocean model was employed, enabling an in-depth examination of the intricate interplay between meteorological and tidal forcings. The study revealed a significant finding: the lag in signal propagation plays a pivotal role in determining how these signals impact the dynamics of the bays. The astronomical signal exhibits a minimal lag along the coast (1 minute), and leads to water level differences between the sea and the coastline, resulting in the generation of tidal currents at the bay entrances. On the other hand, the remote meteorological signal, with a stronger signal lag along the coast (4.92 hours), leads to the creation of water level difference between the bay’s entrances, inducing significant fluxes along the narrow Ilha Grande Channel.

This paper analyzes low-Earth orbit (LEO) satellite downlinks when an airborne interference source moves parallel to the satellite trajectory by considering the relative angle differences be-tween the satellites and the interference sources. To make the experimental interference situations more like actual environments, the LEO trajectories are obtained from two-line element set (TLE) data. Airborne interference sources with various altitudes move parallel to the LEO trajectories, and the jamming to signal (J/S) ratio is calculated based on the relative angle differences between the ground station, the LEO satellite, and the interference source. In order to calculate the relative angle difference psi, the coordinates of the satellite and the interference source are converted from the World Geodetic System 1984 (WGS84) to the ground station-centered east-north-up (ENU) system. By applying the relative angle difference psi, we can obtain the sidelobe gain of the ground station antenna in the direction from which the interference comes. The results of the study confirm that, from a J/S ratio perspective, the distances between the ground station, LEO satellite, and airborne interference source are important, and in particular, the relative angle difference psi between the interference source and the satellite is more critical factor.

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

Disorder of S-adenosylhomocysteine hydrolase (AHCY) activity leads to the potentially lethal rare disease AHCY deficiency, first described in 2004 by Baric and co-workers [1]. In order to shed new light on molecular aspects of the disease, in particular changes at transcriptome level, we enabled knock-down of AHCY expression in model systems such as the colon cancer cell line SW480 to simulate the environment occurring in AHCY deficiency patients. Further, we per-formed deep sequencing of mRNA, followed by differential expression and molecular pathway analysis. Fifteen differentially expressed networks were identified, and interestingly, we found a predicted effect of AHCY down-regulation on the expression of the Lymphoidphoid enhanc-er-binding factor 1 (LEF1) gene, indicating changes in the TCF4/LEF1 complex. LEF1, a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a down-stream mediator of the Wnt/β-catenin signaling pathway [2]. LEF1 is essential in stem cell maintenance, and especially in its role in epithelial-mesenchymal transition (EMT). Western blot analysis of LEF1 protein expression confirmed our transcriptomic data predictions and revealed significantly increased LEF1 protein in AHCY- deficient cells, providing a novel link between AHCY and cancer cell phenotype.

The paper discusses the classification of fuzzy metrics based on their continuity conditions, dividing them into Erceg, Deng, Yang-Shi, and Chen metrics. It explores the relationships between these types of fuzzy metrics, concluding that a Deng metric in [0,1]-topology must also be Erceg, Chen, and Yang-Shi metrics. The paper also proves that the product of countably many Deng pseudo-metric spaces remains a Deng pseudo-metric space, and demonstrates some σ-locally finite properties of Deng metric space. Additionally, the paper constructs two interrelated mappings based on normal space and concludes that if a [0,1]-topological space is T1 and regular, and its topology has a σ-locally finite base, then it is Deng metrizable, and thus Erceg, Yang-Shi, and Chen metrizable as well.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Staphylococcus aureus is a major food-borne pathogen. The ability of S. aureus to produce biofilm is a significant virulence factor triggering its persistence in hostile environments. In this study, we screened a total of 420 different food samples and human hand swabs to detect S. aureus and to determine their biofilm formation ability. Samples analyzed were meat, milk, egg, fish, fast foods, and hand swabs. S. aureus were detected by culturing, staining, biochemical, and PCR. Biofilm formation ability was determined by Congo Red Agar (CRA) plate and Crystal Violet Microtiter Plate (CVMP) tests. The icaA, icaB, icaC, icaD, and bap genes involved in the synthesis of bio-film-forming intracellular adhesion compounds were detected by PCR. About 23.81% (100/420; 95% CI: 14.17-29.98%) samples harbored S. aureus as revealed by detection of the nuc gene. CRA plate revealed 20% of S. aureus isolates as strong biofilm producers, while 69% and 11% as in-termediate and non-biofilm producers, respectively. By the CVMP staining method, 20%, 77%, and 3% of the isolates were found strong, intermediate, and non-biofilm producers. Furthermore, 21% of S. aureus isolates carried at least one biofilm-forming gene, where icaA, icaB, icaC, icaD, and bap genes were detected in 15%, 20%, 7%, 20%, and 10% of the S. aureus isolates, respectively. Bivariate analysis showed high significant correlations (p<0.001) between any of the two adhesion genes of S. aureus isolates. To the best of our knowledge, this is the first study in Bangladesh describing the detection of biofilm-forming S. aureus from foods and hand swabs with molecular-based evidence. Our findings suggest that food samples should be deemed a potential reservoir of biofilm-forming S. aureus that indicates a potential public health significance.

The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis. Whilst hydroxylation has been thoroughly described as the major and canonical modification of the HIF-α subunits, regulating both HIF stability and activity, a range of other post-translational modifications decorating the entire protein play also a crucial role in altering HIF localisation, stability, and activity. These modifications, their conservation throughout evolution and their effects on HIF-dependent signalling are discussed in this review.

Titanium dioxide (TiO₂) micro and nano architectures have been intensively studied in the past years because of many varied applications in environmental, energy conversion, and storage fields, such as heterogeneous catalysis, dye-sensitized solar cells, lithium/sodium ion batteries, lithium-sulfur (Li-S) batteries, and bio-nanotechnology, etc. Especially the surface and interface structures in the TiO₂ structures play important roles in those applications. This mini review article focuses on TiO₂ micro and nano architectures with the prevalent crystal structures (anatase, rutile, brookite, and TiO₂(B)), and summarizes major advances in the surface and interface engineering and applications in environmental and electrochemical applications. We present the principles and growth mechanisms of TiO₂ nanostructures via different strategies, with an emphasis on rational control of the surface and interface structures. We further discuss the applications of TiO₂ micro and nano architectures in photocatalysis, lithium/sodium ion batteries, and Li-S batteries. Throughout the discussion, the relationship between the device performance and the surface structures of TiO₂ micro/nano structures will be highlighted. Then we discuss the phase transitions of TiO₂ nanostructures and possible strategies of improving the phase stability. The review concludes with a perspective on the current challenges and future research directions.

Ulleung County, one of the most medically vulnerable areas in South Korea, requires public attention because of the high incidence of liver cancer. This study was conducted as a part of the Ulleung Liver Cancer Prevention and Management Project. The purpose of this study was to estimate the community prevalence of hepatitis B and C viruses and to identify the associated risk factors. The Project’s interagency workgroup established a procedure for conducting blood sampling and health behavior surveys at the Ulleung Public Community Health Center. A total of 1,792 residents aged 40 years and older voluntarily participated in the study between 2019 and 2022. The hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (anti-HCV) positive rates in Ulleung were 7.19% and 1.37%, respectively. Low education level and lifetime smoking were associated with HBsAg positivity, whereas cupping therapy at non-medical institutions was associated with anti-HCV positivity. The odds of HBs Ag positivity were lower among those with tattoos than among those without. There was a difference in the risk factors associated with hepatitis B and C viral infection. While a high HBs Ag positivity rate alone may not fully explain the high incidence of liver cancer in Ulleung, it may be a contributing factor.

This paper presents the work done to transition the lab scale synthesis (1 g) to a large scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol; a new pharmaceutical for treatment of antibiotic resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab scale synthesis was transformed to a safe and easy to handle flow chemistry step. Additionally, the paper presents an OSHA recommended safety assessment of the active compound E, performed by Fauske and Associates, LLC.

C-terminal Src kinase (CSK) is the major inhibitory kinase for Src family kinases (SFKs) through phosphorylation of their C-tail tyrosine site, and regulates various cellular activities in association with SFKs functions. As a cytoplasmic protein, CSK need be recruited to the plasma membrane to regulate SFKs activities. The regulatory mechanism for CSK activity and its subcellular localization remains largely unclear. In this work, we developed a genetically encoded biosensor based on fluorescence resonance energy transfer (FRET) to visualize CSK activity in live cells. The biosensor with optimized substrate peptide confirmed crucial Arg107 site in CSK SH2 domain, and displayed sensitivity and specificity to CSK activity while little responses to co-transfected Src and Fyn. FRET measurements showed CSK having relatively mild level of kinase activity in comparison to Src and Fyn ones in rat airway smooth muscle cells. The biosensor tagged with different submembrane-targeting signals detected CSK activity at both non-lipid raft and lipid raft microregions, while showed higher FRET level at non-lipid ones. Co-transfected receptor-type protein tyrosine phosphatase alpha (PTPα) had inhibitory effect on the CSK FRET response. The biosensor didn’t detect obvious changes of CSK activity between metastatic cancer cells and normal ones. In conclusion, a novel FRET biosensor was generated to monitor CSK activity, and demonstrated CSK activity existing in both non-lipid and lipid raft membrane microregions while more present at non-lipid ones.

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA inter-ference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

Recent years have experienced an increase in construction and demolition waste (C&amp;DW), which is the most significant solid waste stream. C&amp;DW is contributing to exceeding all planetary boundaries and presents a range of other issues. In order to better understand the existing research on C&amp;DW, a global bibliographic analysis was undertaken through seven groups of keyword searches and the results visualised using VOCviewer. The results show that C&amp;DW receives only a modest research attention compared to other areas of waste, and this is despite an exponential increase in C&amp;DW research since 2016. The analyses also show that concrete is the most researched material in terms of C&amp;DW, and that reuse, recycling, and circular economy are so far attracting only proportionally modest research attention. This signals a need for further acceleration of the C&amp;DW research, and specifically for more research on reuse, recycling, and circular economy for materials other than concrete.

In order to obtain the good match between yield strength and low-temperature toughness, the short-time partial austenitization (SPA) process was employed for V-microalloying 0.22C-5.24Mn steel. The initial microstructure after intercritical tempering was dual-phase ferrite and reversed austenite (RA), while the final microstructure was consisted of ferrite, RA and secondary martensite (SM) after subjected to SPA process. (V, Mo)C with disc-like morphology mainly precipitated during intercritial tempering, and the aspect ratio of particle decreased, leading to the appearance of near-spherical morphology. After subjected to SPA process, the resultant multiphase hierarchical microstructure (three layers: out layer of ferrite, interlayer of SM and inner layer RA) enabled high yield strength of 1097 MPa, total elongation of 14%, and impressive impact energy of 33.3 J at -20 °C. The strengthening contribution of (V, Mo)C precipitation was estimated about 108 MPa.

Diversity-generating retroelements (DGRs) are prokaryotic systems providing rapid modification and adaptation of target proteins. In phages, the main targets of DGRs are receptor-binding proteins that are usually parts of tail structures and the variability of such host-recognizing structures enables phage adaptation to changes on the bacterial host surface. Sometimes, more than one target gene containing a hypermutated variable repeat (VR) can be found in phage DGRs. The role of mutagenesis of two functionally different genes is unclear. In this study, several phage genomes that contain DGRs with two target genes were found in the gut virome of healthy volunteer. Bioinformatics analysis of these genes indicated that they encode proteins with different topology; however, both proteins contain the C-type lectin (C-lec) domain with a hypermutated beta-hairpin on its surface. One of the target proteins belongs to a new family of proteins with a specific topology: N-terminal C-lec domain followed by one or more immunoglobulin domains. Proteins from the new family were named tentaclins after TENTACLe+proteIN. The genes encoding such proteins were found in the genomes of prophages and phages from the gut metagenomes. We hypothesized that tentaclins are involved in binding either to bacterial receptors or intestinal/immune cells.

Monitoring snowmelt dynamics in mountains is crucial to understand water releases downstream. Sentinel-1 (S-1) synthetic aperture radar (SAR) has become one of the most widely used techniques to achieve this aim due to its high frequency of acquisitions and all-weather capability. This work aims to understand the possibilities of S-1 SAR imagery to capture snowmelt dynamics and related changes in streamflow response in semiarid mountains. The results proved that S-1 SAR imagery was able not only to capture the final spring melting but also all melting cycles that commonly appear throughout the year in these types of environments. The general change detection approach to identify wet snow was adapted for these regions using as reference the average S-1 SAR image from the previous summer, and a threshold of -3.00 dB. In addition, four different type of melting runoff onsets depending on physical snow condition were identified. When translating that at the catchment scale, distributed melting runoff onset maps were defined to better understand the spatiotemporal evolution of melting dynamics. Finally, a linear connection between melting dynamics and streamflow was found for long-lasting melting cycles, with a determination coefficient (R2) ranging from 0.62 to 0.83 and an average delay between the melting onset and streamflow peak of about 21 days.

The integration of deep learning methods, especially Convolutional Neural Networks (CNN), and Synthetic Aperture Radar Automatic Target Recognition (SAR ATR) has been widely deployed in the field of radar signal processing. Nevertheless, these methods are frequently regarded as black-box models due to the limited visual interpretation of their internal feature representation and parameter organization. In this paper, we propose an innovative approach named C-RISE, which builds upon the RISE algorithm to provide a post-hoc interpretation technique for black-box models used in SAR Images Target Recognition. C-RISE generates saliency maps that effectively visualize the significance of each pixel. Our algorithm outperforms RISE by clustering masks that capture similar fusion features into distinct groups, enabling more appropriate weight distribution and increased focus on the target area. Furthermore, we employ Gaussian blur to process the masked area, preserving the original image structure with optimal consistency and integrity. C-RISE has been extensively evaluated through experiments, and the results demonstrate superior performance over other interpretation methods based on perturbation when applied to neural networks for SAR image target recognition. Furthermore, our approach is highly robust and transferable compared to other interpretable algorithms, including white-box methods.

Revealing the time structure of physical or biological objects is usually performed thanks to the tools of signal processing like the fast Fourier transform, Ramanujan sum signal processing and many other techniques. For space-time topological objects in physics and biology, we propose a type of algebraic processing based on schemes in which the discrimination of singularities within objects is based on the space-time-spin group SL(2,C). Such topological objects possess an homotopy structure encoded in their fundamental group and the related SL(2,C) multivariate polynomial character variety contains a plethora of singularities somehow analogous to the frequency spectrum in time structures. Our approach is applied to an Akbulut cork in exotic R4, to an hyperbolic model of topological quantum computing based on algebraic surfaces and to microRNAs in genetics. Such diverse topics reveal the manifold of possibilities of using the concept of a scheme spectrum.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3-9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS) Compared with the control group (n=34), cardiac damage was significantly lower in the apheresis group (n=32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65-177) d whether the effect of CRP apheresis is clinically maintained. After this time period wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of &lt;0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of &gt;0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (-5.4%; p=0.05), a better LVEF (+6.4%; p=0.03), and an improved CS (-6.1%; p=0.005). No significant improvement, however, was observed for LS (-2.9%; p=0.1). These data suggest a sustained positive effect of CRP apheresis on the heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

Leucine-rich α-2 glycoprotein1 (LRG1) is a member of the leucine-rich repeat (LRR) family that was implicated in multiple diseases including cancer, aging and heart failure as well as diabetes and obesity. LRG1 plays a key role in diet-induced hepatosteatosis and insulin resistance by mediating the crosstalk between adipocytes and hepatocytes. LRG1 also promotes hepatosteatosis by upregulating de novo lipogenesis in the liver and suppressing fatty acid β oxidation. In this study, we investigated the association of LRG1 with obesity markers including leptin and other adipokines in adolescents (11-14 years; n=425). BMI-for-age classification based on WHO growth charts was used to define obesity. Plasma LRG1 was measured by ELISA while other markers were measured by multiplexing assay. Median (IQR) of LRG1 levels was higher in obese [30 (25, 38) µg/mL] and overweight [30 (24, 39) µg/mL] adolescents, compared to normal-weight participants [27 (22, 35) µg/mL]. The highest tertile of LRG1 had an OR [95%CI] of 2.55 [1.44, 4.53] for obesity. LRG1 was positively correlated to plasma levels of HsCRP (R=0.2), Leptin (R=0.2) and Chemerin (R=0.24) with p<0.001. Additionally, it was positively associated with plasma level of IL6 (R=0.17) and IL10 (R=0.14) but not TNF-α. In conclusion, LRG1 levels are increased in obese kids and associate with increased levels of adipogenic markers. These results suggest the usefulness of LRG1 as an early biomarker for obesity and its related pathologies in adolescents.

The construction of carbon-carbon bonds by direct involvement of two unactivated carbon-hydrogen bonds, without any directing group, ensures an high atom economy of the entire process. Here it is described a simple protocol for the Pd(II)/Cu(II)-promoted intermolecular cross-dehydrogenative coupling (CDC) of 5-arylimidazoles, benzimidazoles, benzoxazole and 4,5-diphenylimidazole at their C-2 position with functionalized styrenes. This specific CDC, known as Fujiwara-Moritani reaction or oxidative Heck coupling, allowed also the C-4 alkenylation of the imidazole nucleus when both 2 and 5 positions are occupied.

The identification and molecular characterization of cellular hierarchies in complex tissues is key to understanding both normal cellular homeostasis and tumorigenesis. The mammary epithelium is a heterogeneous tissue consisting of two main cellular compartments, an outer basal layer containing myoepithelial cells and an inner luminal layer consisting of estrogen receptor-negative (ER⁻) ductal cells and secretory alveolar cells (in the fully functional differentiated tissue) and hormone-responsive estrogen receptor-positive (ER⁺) cells. Recent publications have used single-cell RNA-sequencing (scRNA-seq) analysis to decipher epithelial cell differentiation hierarchies in human and murine mammary glands, and reported the identification of new cell types and states based on the expression of the luminal progenitor cell marker KIT (c-Kit). These studies allow for comprehensive and unbiased analysis of the different cell types that constitute a heterogeneous tissue. Here we discuss scRNA-seq studies in the context of previous research in which mammary epithelial cell populations were molecularly and functionally characterized, and identified c-Kit⁺ progenitors and cell states analogous to those reported in the recent scRNA-seq studies.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

The goal of farmers operating in a market economy is to maximise profit. In the face of the changing political situation, the main social interest, besides food security, should be energy security. This article aims to indicate the direction of agricultural policy development so that it guarantees both the economic security of producers—farmers—and Europe’s energy security. The work uses data obtained from the agri benchmark Cash Crop database. DEA method and stepwise multiple regression were used. The research showed that plants are already grown in Europe which will ensure high energy efficiency of production without compromising farm financial results (including oats, peas and winter rye) and that improving the involvement of certain inputs results in improved production efficiency (among others, by expenditure on agricultural advisory services). The significance of the presented research results from the fact that the recent COVID pandemic and escalation of the military conflict in Ukraine have led to a renewed interest in the concept of EU energy security, i.e. generation of generating the greatest possible amount of energy within the EU, to be used both for food and non-food purposes.

The effect of H2S with high concentrations on catalytic dry reforming of methane (DRM) process has seldom been focused on previously. Herein, a thermodynamic analysis of the DRM reactions in the presence of H2S with the concentration varying in 0-20 vol% was conducted firstly. Several typical types of catalysts including MgO, NiO/MgO and LaNiO3 in different states were prepared for executing DRM at 800 C, 0.1 MPa in the feed of 20 vol% CO2 and 20 vol% CH4 balanced with N2. The catalytic performance of each catalyst for DRM process under conditions of absence and presence of H2S was compared. A promotion effect of increasing H2S concentration on both the conversions of CO2 and CH4 and the molar yields of CO and H2 was observed on all the catalysts especially the MgO and the pristine NiO/MgO. While a significant decline in catalytic activity of either the reduced NiO/MgO or the reduced LaNiO3 catalyst after adding H2S, moderate reactant conversions still sustained. The results of process analysis and catalyst structure characterization suggest that H2S participation can contribute to the increment in CO2 and CH4 conversion, and active S-adsorbed species may play the key role of catalysis in the reactions involving H2S.

Banana bunchy top virus (BBTV) was recently detected in Mozambique and appears to be limited to the provinces of Gaza, Maputo and Zambezia, but it has great potential to spread to other provinces. Despite its importance, nothing is known about the BBTV isolates that occur in Mozambique. In this study, the sequences of the S and R genes of 40 isolates chosen as representatives of samples collected previously from eleven farms of the four administrative posts of the district of Chóckwè, Gaza province, were sequenced and analyzed. The S-DNA nucleotide sequences of the analyzed isolates were highly conserved, with identity ranging from 97% to 100%. The same was observed for the R-DNA sequences, with most identities ranging between 98% and 100% among the isolates from Chókwè and above 90% when compared to the isolates from GenBank. The phylogenetic analysis showed that the Mozambican BBTV isolates belong to the Pacific-Indian Oceans (PIO) group, showing greater proximity to the isolate JQ820453 from Malawi than to the isolates from sub-Saharan countries, which were grouped in a distinct subclade. This is the first study conducted to determine the molecular characteristics of BBTV isolates present in Mozambique.

Hydrogen plays an important role in the implementation of Australia’s Net-Zero Strategy. It competes with lithium-ion rechargeable batteries in the electrification of Australian land transportation sector, and can provide an alternative energy storage medium for the greening of the country’s electrical grid system. This paper reviews the role hydrogen plays in the current government’s Net-Zero strategy, and investigates the potential role of other bioenergy sources. It is found that hydrogen and batteries play essentially complementary roles in reducing transport emissions, and that the former energy source is more suited to the operation of long-distance commercial service vehicles than batteries. It is suggested that bioenergy fuels such as biomethane, second generation biofuels and HVO can provide suitable bridging alternatives in the event that Australia’s EV strategy is unable to meet the 2030 target.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

This paper is the continuation of a previous study, which highlighted some inconsistencies in the RILEM guidelines for the interpretation of the diagonal compression test. Although improved compared to the ASTM guidelines, in fact, the RILEM guidelines underestimate the state of hydrostatic stress induced by the diagonal compression test at the center of the wallette. The new interpretation of the diagonal compression test proposed in this article shows that the RILEM guidelines actually underestimate both the hydrostatic and the deviatoric stress states at the center of the wallette. The new formulation complies with the linear elastic theory and allows us to use the the diagonal compression test to identify the three elastic coefficients of masonry. In particular, it allows the identification of the Poisson ratio, which instead takes on a conventional value in the RILEM and ASTM guidelines. The difference of one order of magnitude between the conventional and proposed Poisson’s ratio is in agreement with the experimental results on another brittle material, namely concrete. Finally, the new proposal fills the gap between the results provided by the two tests usually performed to identify the shear behavior of masonry: the diagonal compression test and the shear-compression test.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

Запропонована методика спрямована на визначення та прогнозування технічного стану елементів мосту, що може слугувати прогресивним інженерним інструментом для оцінки надійності та довговічності. Розроблено на основі фундаментальних досліджень, які узагальнюють досвід вивчення фізико-механічних і фізико-хімічних властивостей матеріалів мостових конструкцій, що експлуатуються в реальних умовах. Теоретичною основою методики є модель надійності та прогнозування залишкового ресурсу елементів мосту на основі теорії Маркова. Розроблена методика призначена для оцінки технічного стану окремих елементів мосту з подальшою комплексною оцінкою всієї конструкції. За показник технічного стану прийнята надійність при експлуатації. Цей кількісний показник надійності в моделі є критерієм для: оцінки рівня безпеки елементів мосту; ранжування елементів мосту за необхідністю для конкретних видів ремонту, реконструкції або заміни; стратегічне планування витрат на ремонт або реконструкцію в умовах обмеженого фінансування; прогнозування залишкового ресурсу елементів. Для застосування розробленої методики запропоновано алгоритм оцінки та прогнозування технічного стану мостів. Було проведено математичний експеримент розробленої методики, який підтвердив адекватність висунутої гіпотези, тобто використання моделі надійності та прогнозування залишкового ресурсу елементів мосту. По-перше, запропоновано триступеневий механізм уточнення технічного стану мосту, суттєво підвищення точності розрахунків. Тому розроблена методика має практичне значення і може слугувати основою для інформаційно-аналітичних систем управління станом мостів.

This paper presents a concise exploration of the synthetic biology currently to artificially 1 create life, juxtaposed against natural life’s emergence over Earth’s 4.5-billion-year history. It explores 2 the complexities of life’s origins, sustaining factors, and the consequences of synthetic life creation, 3 addressing key scientific milestones such as the Urey-Miller experiment and Jacques Monod’s pro- 4 posals. The narrative navigates through the roles of energy, Maxwell’s demons, bifurcations, and 5 genetic information in the emergence and evolution of complex biological systems. Despite significant 6 strides in genetic engineering, the challenge of creating life from scratch persists, necessitating a deep 7 understanding of diverse scientific disciplines. While synthetic biology holds promise for medicine 8 and biotechnology, the creation of truly autonomous synthetic life forms raises ethical concerns. The 9 paper also stresses the imperative for careful ethical evaluation of the societal and environmental 10 implications arising from these advancements.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

Work from the last years indicate that the extracellular matrix (ECM) plays a direct role in vari-ous cellular processes including proliferation, migration and differentiation. Besides homeostat-ic processes, its regulatory function in inflammation becomes more and more evident. In in-flammation like inflammatory bowel disease, the ECM composition is constantly remodeled which can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we will provide an over-view of relevant diagnostic methods focusing on ECM changes.

This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their potential biomedical therapeutic and industrial applications. Sinigrin and glucoraphanin are converted by the -sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence mechanism plants have developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks and nematodes. These compounds display biological activities in a number of mammalian physiological processes and potential biotherapeutic application. Glucosinolates may be useful in bio-fumigation and treatment of biofilms which occur on plant equipment and medical implants formed by problematic pathogenic bacteria such as Pseudomonas aeruginosa. AITC and SFN display similar antibiotic activity as Vancomycin in the treatment of bacteria listed by the World Health Organization as antibiotic-resistant "priority pathogens".AITC and SFN also display bioactivity in cancer chemoprevention through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. The glucosinolates have found application in the prevention of bacterial and fungal spoilage of food substances during processing and in advanced food packaging formats which improve the shelf-life of food products.

Adaptive Sliceable-Bandwidth Variable Transceivers (S-BVTs) are key enabler for future optical networks. In particular, those based on Discrete MultiTone (DMT) modulation and Direct Detection (DD) can be considered a flexible solution suitable to address the cost efficiency requirement of optical metro networks. In this paper, we propose to use this cost-effective S-BVT option/implementation in optical metro networks adopting switching nodes based on Semiconductor Optical Amplifier (SOA) technology. Bit loading (BL) and power loading (PL) algorithms are applied to the Digital Signal Processing (DSP) modules, to maximize the performance and/or the capacity as well as enhance the flexibility and adaptability of the system. Our analysis considers switching nodes based on SOAs with and without filtering elements and fiber spans of 25 km. We present the results up to 100 km, with and without SOA-based nodes. Firstly, we analyze the adaptive BVT transmission using the Margin Adaptive (MA) BL/PL algorithm at a fixed bit rate of 28 Gb/s. The possibility of controlling the SOAs current is a key factor to face the transmission impairments due to the fiber and the filtering elements. We also analyze the system considering Rate Adaptive (RA) transmission at a fixed target BER of 3.8·10⁻³, showing that a maximum capacity above 34 Gb/s can be achieved for a single span of 25 km. Although the cascading of filtering elements still constitutes a limiting factor, we show that an improvement of the net bit rate performance can be obtained thanks to the combined use of S-BVT and SOA technology at the switching nodes, resulting in a promising approach for designing future optical metro networks.

In order to meet the military requirements of the fuze, such as precision strike, efficient mutilates ability and low collateral damages, the microminiaturization is an inevitable trend of secure system. Based on the silicon-based MEMS S&A device designed by our term, the design principles of each module and fabrication process are introduced. The average fracture strength and Young's modulus of the silicon are 726 MPa and 175 GPa from the tensile test, respectively. From Hopkinson impact experiment, we can get the threshold-value judging mechanism being safety under the impact overload of 20526 g, and this value is much more than the standard of the drop overload 12000g; the arming value under the centrifugal overload obtained from theory, simulation and experiment is at the range of 28200 g and 32000 g, it shows that the threshold-value judging mechanism can be arming compared with the value 35951g of design principle. Therefore, the threshold-value judging mechanism can meet the design requirements of overload. Furthermore, the relationship of fracture threshold-values obtained by different theories is found out through parametric design method, as shown in Figure 14, it provides the theory evidence to the follow parametric design.

This research paper aims to explicate the complex issue of the Riemann's Hypothesis and ultimately presents its elementary proof. The method implements one of the binomial coefficients, to demonstrate the maximal prime gaps bound. Maximal prime gaps bound constitutes a comprehensive improvement over the Bertrand's result, and becomes one of the key elements of the theory. Subsequently, implementing the theory of the primorial function and its error bounds, an improved version of the Gauss' offset logarithmic integral is developed. This integral serves as a Supremum bound of the prime counting function Pi(n). Due to its very high precision, it permits to verify the relationship between the prime counting function Pi(n) and the offset logarithmic integral of Carl Gauss. The collective mathematical theory, via the Niels F. Helge von Koch equation, enables to prove the RIemann's Hypothesis conclusively.

This article provides a detailed analysis of non-invasive techniques for prediction and diagnosis of faults in internal combustion engines, focusing on the application of the Proknow-C and Methodi Ordinatio systematic review methods. Initially, the relevance of these techniques in promoting energy sustainability and mitigating greenhouse gas emissions is discussed, aligning with the Sustainable Development Goals (SDGs) of Agenda 2030 and the Paris Agreement. The systematic review conducted in the subsequent sections offers a comprehensive mapping of the state-of-the-art, highlighting the effectiveness of combining these methods in categorizing and systematizing relevant scientific literature. The results reveal significant advancements in the use of artificial intelligence (AI) and digital signal processors (DSP) to enhance fault diagnosis, as well as underscore the crucial role of non-invasive techniques in minimizing interference in monitored systems. Finally, concluding remarks point towards future research directions, emphasizing the need to develop digital twins for internal combustion engines and identify gaps for further improvements in fault diagnosis and prediction techniques.

Fusing data from many sources helps to achieve higher results of analysis. In this work, we present a new algorithm to fuse data from multiple cameras with data from multiple lidars. This algorithm was developed to increase the sensitivity and specificity of autonomous vehicle perception systems, where the most accurate sensors measuring the vehicle’s surroundings are cameras and lidar devices. Perception systems based on data from one type of sensor do not use complete information and have lower quality. The camera provides two-dimensional images; lidar produces three-dimensional point clouds. We developed a method for matching pixels on a pair of stereoscopic images using dynamic programming inspired by an algorithm to match sequences of amino acids used in bioinformatics. We improve the quality of the basic algorithm using additional data from edge detectors. We also improve the algorithm performance by reducing the size of matched pixels determined by available car speeds. We perform point cloud densification in the final step of our method, fusing lidar output data with stereovision output. We implemented our algorithm in C++ with Python API, and we provided the open-source library named Stereo PCD. This library very efficiently fuses data from multiple cameras and multiple lidars. In the article, we present the results of our approach to benchmark databases in terms of quality and performance. We compare our algorithm with other popular methods.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

Biological neural network (BNN) is the core brain for creature to accomplish its intelligent behaviors through unique network structure and mechanisms. It also inspires controlling human-designed autonomous agents including robots to generate more advanced intelligent behaviors by mimicking the neural control mechanism of creatures at a deeper and more interactive level. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of cellular synapse. The neural network simulation integrates computational programming and visualization of neurons and synapse connections of C. elegans, containing the specific controllable circuits summarization with their dynamic characteristics within the whole network. To illustrate its particular intelligent control capability in terms of robotics, we introduce the first innovative methodology for applying the BNN model to a 12-legged robot’s movement control based on the established numerical simulation platforms. We accomplished and designed two methods and corresponding encoding processes, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of BNN. Both simulation and experiment results indicate that the robot exhibits stronger autonomy and more intelligent moving performance under the control of BNN. We then summarized the contributions for digitalizing the C. elegans’ whole-brain neural network in real-time and utilizing it to control robot in a closed loop to validate its advanced intelligence control ability in terms of a scientific robot.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

SORL1 gene encodes LR11/SorLA, a protein that binds -amyloid precursor protein (bAPP) and drives its intracellular trafficking. SORL1 mutations occurring frequently in a subset of familial cases of Alzheimer’s disease (AD) have been documented but their pathogenic potential is not yet clear and questions remain concerning their putative influence on the physiopathological processing of bAPP. We have assessed the influence of three SORL1 mutations that were described as likely disease-causing and that were associated with either benign (SorLA924) or severe (SorLA141 and SorLA511) AD phenotypes. We examined the influence of wild-type and mutants SorLA in transiently transfected HEK293 cells expressing either wild-type or Swedish mutated bAPP on bAPP expression, secreted Ab and sAPPa levels, intracellular Ab40 and Ab42 peptides, APP-CTFs (C99 and C83) expressions, a-, b- and g-secretases expressions and activities as well as Ab and CTFs-degrading enzymes. These paradigms were studied in control conditions or after pharmacological proteasomal modulation. We also established stably transfected CHO cells expressing wild-type SorLA and established the colocalization of wild-type SorLA and bAPP. Overall, although we mostly confirmed previous data concerning the influence of wild-type SorLA on bAPP processing, we were unable to evidence significant alterations triggered by our set of SorLA mutants, whatever the cells or pharmacological conditions examined. Our study however does not rule out the possibility that other AD-linked SORL1 mutations could indeed affect bAPP processing and that pathogenic mutations examined in the present study could interfere with other cellular pathways/triggers in AD.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

Data from ocean color (OC) remote sensing are considered a cost-effective tool for the study of biogeochemical processes globally. Satellite-derived chlorophyll, for instance, is considered an Essential Climate Variable since it is helpful in detecting climate change impacts. Google Earth Engine (GEE) is a planetary scale tool for remote sensing data analysis. Along with OC data, such tools allow an unprecedented spatial and temporal scale analysis of water quality monitoring in a way that has never been done before. Although OC data have been routinely collected at medium (~1 km) and more recently at high (~250 m) spatial resolution, only coarse resolution (≥4 km) data are available in GEE, making them unattractive for applications in the coastal regions. Data reprojection is needed prior to making OC data readily available in the GEE. In this paper, we introduce a simple but practical procedure to reproject and ingest OC data into GEE. The procedure is applicable to OC swath (Level-2) data and is easily adaptable to higher-level products. The results showed consistent distributions between swath and reprojected data, building confidence in the introduced framework. The study aims to start a discussion on making high resolution OC data readily available in GEE.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique at-tributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two preg-nancies, which occurred 4 years apart, without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no evidence of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (> 100 mg/L) and signs of respiratory failure were treated with CRP apheresis. 2-12 CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest x-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. All patients had comorbidities. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation require-ments. Our clinical observations regarding the here presented seven patients support the hypoth-esis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

Rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to 9-tetrahydrocannabinol (9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that 9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg 9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to 9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, 9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACC, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, was also observed in these 9-THC-exposed offspring. Collectively, these findings indicate that prenatal 9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

Endometrial Cancer (EC) is the sixth most commonly occurring cancer in women with 380 000 cases in 2018. Sadly, EC morbidity and mortality are continuously increasing, therefore the medical society have a substantial need for an accurate and inexpensive diagnostic test for EC early detection and a prognostic tool for treatment planning and evaluation. Considering experience with different types of cancers C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential and in view of EC authors, this paper reviewed the following databases for metanalysis, randomized controlled trials and review articles published up to June 2020: Pubmed, Scopus, Google scholar and ClinicalKey. Studies indicate CRP >3.33 mg/l correlate with EC incidence with HR = 2.29 (p<0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Preoperational and postoperational CRP, as well as its dynamic change are independent prognostic factors for EC and are more reliable if analyzed together. However, CRP-to-albumin ratio as well as Glasgow Prognostic Scale have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

The fourth Industrial Revolution, well-known as “Industry 4.0”, based on the integration of information and communication technologies, has introduced significant improvements in manufacturing. However, vision systems still experience various impracticalities in dealing with the effect of complex lighting on the systems platform. Therefore, a machine vision system for automatic identification of pen parts under varying lighting conditions at a digital learning factory is proposed. The developed vision system presents a straightforward approach by effectively minimizing the environmental lighting effect on the identification process. First, the obtained information of the designed vision framework is exported to a program, where a reduction of non-uniform illumination is achieved through the implementation of Retinex image enhancement techniques. Then, the color-based Fuzzy C-means (FCM) algorithm, including improved mark watershed segmentation, is employed for pen parts object classification. Finally, the position features of the selected pen part are reported. The process applied to a total number of 210 upper pen parts (caps) and 241 lower pen parts (tubes) images under different lighting scenarios. Results indicate that average parts identification precision for cap and tube parts is different and equals to 98.64% and 95.26%, respectively. The present methodology provides a promising scheme that can be feasibly adapted for other industrial Color-based object recognition applications.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

This paper proposes a theoretical silicon dioxide (SiO2) solar cell based dielectric metamaterial unit surface consisting of zinc oxide (ZnO) periodic nanorods of bandgap energy of 2.2-2.4eV. It evaluates the absorptive efficiency of the film using S-parameter and Z-parameter testing of magnitude, return/insertion loss, and impedance matching with respect to a frequency band of 0.0014-10.5THz. Terahertz applications of the result are considered due to potential scope for infrared (IR) and microwave (MW) spectral selectivity with ZnO. Calculations of input n-impedance and loss tangents are also presented with emphasis on the exhibition of antireflection to gauge the performance of the thin-film meta-surface in tandem solar cells. The data for the reflectance parameters of this structure, primarily the S11 loss and impedance matching (dB/dB10) are compared to those of prior investigations with different metamaterial coatings on SiO2 solar photovoltaic cells, as well as ZnO nanorods used in photovoltaic applications, to ascertain the cylindrical meta-surface structure with the preset thicknesses of the study being an effective anti-reflector. Application can be extended to other broadband domains requiring plasmonic graded refractive surfaces, in further work.

Seedling establishment is often a critical bottleneck to revegetation of mine tailings and similar substrates with a low capacity to retain water and plant nutrients. Biochar and deactivated yeast are potential sustainable, low-cost materials with high nutrient- and water-holding capacity that could be used in this context as seed coatings to aid in seedling establishment on challenging sub-strates. We conducted a greenhouse study to assess the effectiveness of biochar and deactivated yeast, applied alone in a factorial combination, as seed coatings, on the germination, establish-ment, and early growth of white clover (Trifolium repens) and purple prairie clover (Dalea pur-purea). Coated seeds were applied to a mine tailing, a coarse granitic sand, and potting soil mix substates; seedling establishment and growth were monitored over 75 days. Results indicate strong interactive effects of seed coatings with species and substrate. Biochar coatings enhanced seedling establishment of Trifolium, with biochar or biochar plus yeast coatings giving the best results. In some cases, these effects persisted throughout the experiment: biochar coatings resulted in a ~5-fold increase in Trifolium biomass at harvest for plants in the potting soil mix but had neutral effects on sand or tailings. Biochar seed coatings also enhanced Dalea germination in some cases, but benefits did not persist. Our results indicate that biochar-based seed coatings can have lasting effects on plant growth well beyond germination, but also emphasize highly spe-cies-specific responses that highlight the need for further study of broader patterns and mecha-nisms.

The viewpoint and reaction of a country towards climate change are shaped by its political, cultural, and scientific backgrounds, in addition to the distinct characteristics of its evolving climate and the anticipated and actual consequences of the phenomenon in the times ahead. A region's climate has a significant impact on how water is managed and used, mostly in the primary sector (agroforestry systems, livestock, and agriculture), and both the distribution of ecosystem types and the amount and spreading of species on Earth. As a result, the environment and agricultural practices are affected by climate, so evaluating both distribution and evolution is extremely pertinent. Towards this aim, the climate distribution and evolution in the S. Francisco River basin (SFRB) is assessed in three periods (1970−2000, 1981−2022) in the past and 20412060 in the future from an ensemble of GCMs under two SSPs (Shared Socioeconomic Pathways), SSP2-4.5 and SSP5-8.5. The Köppen-Geiger (KG) climate classification system is analyzed, and climate change impacts are inferred for this watershed located in central-eastern Brazil, covering an area equivalent to 8% of the country. Results predict the disappearance of the hot-summer (Csa) and warm-summer (Csb) Mediterranean climates, and a reduction/increase in the tropical savanna with dry winter (Aw)/dry summer (As). A striking increase in the semi-arid hot (BSh-steppe) climate is predicted with a higher percentage (10%) under SSP5-8.5. The Source and the mouth of SFRB are projected to endure the major impacts of climate change that is followed by a predicted increase/decrease in temperature/precipitation. Future freshwater resource availability, and quality for human use will all be impacted. Consequences on ecosystems, agricultural and for the socioeconomic sectors within the SFRB might deepen the current contrasts between regions, urban and rural areas, and even between population groups, thus translating to a larger extent, the inequality that still characterizes Brazilian society. Maps depicting land use and cover changes in the São Francisco River basin from 1985 to 2022 highlight tendencies such as urbanization, agricultural expansion, deforestation, and changes in shrubland and water bodies. Urban areas fluctuated slightly, while cropland significantly increased from 33.57% to 45.45%, and forest areas decreased from 3.88% to 3.50%. Socioeconomic data reveals disparities among municipalities: 74.46% with medium Human Development Index (HDI), 0.59% with very high HDI, and 9.11% with low HDI. Most municipalities have a Gross Domestic Product (GDP) per capita below US$ 6,000. Population distribution maps show a predominance of small to medium-sized urban and rural communities, reflecting the basin's dispersed demographic and economic profile. To build routes towards a shared sustainable goal—namely, to adapt and reduce the expected climate change impacts in SFRB—it is imperative that integrated measures be conducted with the cooperation of stakeholders, local population, and decision-makers.

In this work, an improved collocation method based on the Bernoulli polynomials is presented to solve the Volterra integral equation (VIE) of the second kind. The main idea of the proposed method is to improve the results of the classic Bernoulli collocation method (BCM) by dividing the interval into some sub-intervals and considering the collocation points on each of them. Here, the zeros of the shifted Chebyshev polynomials (SCPs) are considered as collocation points. Then, BCM is applied step by step from the first sub-interval to the last one. By this process, a system of algebraic equations is attained for each sub-interval that could be easily solved. Convergence of the scheme is analyzed. For the purpose of demonstrating the validity, applicability, and efficiency of the suggested scheme several numerical examples are provided. Numerical results illustrate that the accuracy of the improved Bernoulli collocation method (IBCM) is more than BCM.

Colpodella species are free-living opportunistic pathogens that cause human and animal infections and use ticks and flies as vectors. Trophozoite and cyst stages of Colpodella species can be distinguished from stages of the prey Parabodo caudatus using Sam-Yellowe’s trichrome staining. Colpodella species obtain nutrients by attaching to their prey, aspirating the prey’s cytoplasmic contents into a posterior food vacuole and encysting. It is unclear whether both trophozoite and cyst stages are present during infection. Molecular techniques identified Colpodella species in all reported infections. However, no morphological information was reported to aid life cycle stage identification in hosts. This review discusses the increased incidence of Colpodella infection in animals and in vectors and the need to identify stages used for transmission and pathogenesis. The potential for zoonotic infections through tick and fly bites is a public health concern. We previously used Sam-Yellowe’s trichrome staining to identify life cycle stages of Colpodella sp. In order to gain a better understanding of transmission and pathogenesis, identifying Colpodella life cycle stages in infected tissue and in vectors will provide important insights regarding nutrient uptake in hosts by determining whether attachment of trophozoites to host cells occurs, and identifying trophozoites and cysts in infected hosts.

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.