Radio-fluorogenic (RFG) gels become permanently fluorescent when exposed to high-energy radiation with the intensity of the emission proportional to the local dose of radiation absorbed. An apparatus is described, FluoroTome 1, that is capable of taking a series of tomographic images (thin slices) of the fluorescence of such an irradiated RFG gel on-site and within minutes of radiation exposure. These images can then be compiled to construct a 3D movie of the dose distribution within the gel. The historical development via a laboratory-bench prototype to a readily transportable, user-friendly apparatus is described. Instrumental details and performance tests are presented.

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018, to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

Contrary to optical images, Synthetic Aperture Radar (SAR) images are in different electromagnetic spectrum where the human visual system is not accustomed to. Thus, with more and more SAR applications, the demand for enhanced high-quality SAR images has increased considerably. However, high-quality SAR images entail high costs due to the limitations of current SAR devices and their image processing resources. To improve the quality of SAR images and to reduce the costs of their generation, we propose a Dialectical Generative Adversarial Network (Dialectical GAN) to generate high-quality SAR images. This method is based on the analysis of hierarchical SAR information and the “dialectical” structure of GAN frameworks. As a demonstration, a typical example will be shown where a low-resolution SAR image (e.g., a Sentinel-1 image) with large ground coverage is translated into a high-resolution SAR image (e.g., a TerraSAR-X image). Three traditional algorithms are compared, and a new algorithm is proposed based on a network framework by combining conditional WGAN-GP (Wasserstein Generative Adversarial Network - Gradient Penalty) loss functions and Spatial Gram matrices under the rule of dialectics. Experimental results show that the SAR image translation works very well when we compare the results of our proposed method with the selected traditional methods.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

An exposition is undertaken to reveal the significant impact of the time-dependent root parameter, on the stability of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing system. This opens new grounds to stability analysis of non-stationary queueing systems. Potential PSFFA applications of IoT are highlighted.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Background/Objectives: The disparities in internalizing and externalizing symptoms between individuals with versus without neurofibromatosis type 1 (NF1) are poorly understood, based on mixed evidence in the literature. The current meta-analysis aimed to synthesize existing findings on the topic and explore moderators of the group disparities. Method: Electronic databases were searched from inception to March 26th 2024, which identified 59 eligible studies (N of NF1 = 3,182, mean ages 2.38 to 46.4 years). The primary outcome was differences in internalizing and externalizing symptoms between individuals with and without NF1. Data were analyzed using robust variance estimation and random-effects models. Results: Compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression. Conclusions: Findings highlight the importance of including psychosocial needs in monitoring and treating NF1. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development.

Emerging RNA virus infections are a growing concern among domestic bird and poultry industries due to the severe impact it can have on the flock health and economic livelihoods. Avian paramyxoviruses (APMV) are pathogenic, negative sense RNA viruses that cause serious infections in the respiratory and central nervous system. APMV was detected in multiple avian species during the 2017 migration season in Ukraine, and studied using PCR, virus isolation, and sequencing. Of the 4090 wild bird samples, eleven swabs were isolated in chicken embryos and identified for APMV serotype by hemagglutinin inhibition test: APMV-1, APMV-4, APMV-6, APMV-7. At a variety of sites in Ukraine we characterized the virulence of the virus and further analyzed and predicted the potential risks of spillover to immunologically naïve populations. RNA was extracted and amplified using a multiplex-tiling primer approach to encompass full cDNA genomes. Full-length APMV-1 (n=5) and APMV-6 (n=2) genomes were sequenced on an Oxford Nanopore MinION device in Ukraine. All APMV-1 and APMV-6 fusion (F) proteins possessed a monobasic cleavage site, suggesting these APMV were likely low virulence, annually circulating strains. Utilization of this low-cost method will identify gaps in viral evolution and circulation in this understudied but important critical region for Eurasia.

Diuretic resistance is a servomechanism involving superoxide that results from the use of escalating doses of diuretics in the treatment of heart failure. Without intervention this may lead to increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been proposed to explain the benefits of both these drug classes but this paper is the first to explain and propose superoxide induced diuretic resistance as a therapeutic target for the treatment of heart failure.

Background: Sarcopenia is a progressive muscle disorder characterized by muscle wasting, decreased strength, and a substantially elevated risk of developing severe and potentially life-threatening health complications. For decades, muscle wasting has been recognized as a clinical symptom in various severe diseases and conditions. However, with increasing life expectancy and an aging population, sarcopenia has emerged as a prominent age-related condition in primary care, significantly contributing to disability and mortality rates. Aim and Objective: Our goal was to elucidate the clinical characteristics associated with sarcopenia prevalence in postmenopausal women with type 1 osteoporosis. Methodology: 370 postmenopausal osteoporosis patients who routinely visited the physiotherapy department at Ali Fatima Hospital were examined in this cross-sectional investigation. Mean age 64.59 ± 5.85 years, it was discovered that the patients' quality of life, postural stability, muscular strength, and balance were related to the existence of sarcopenia. Conclusion: In summary, among postmenopausal female patients with type 1 osteoporosis, the incidence of sarcopenia was relatively high (90.35%), affecting quality of life in 39.82% of patients, postural instability in 92.21% of patients, and balance in 39.92% of patients.

In this paper, we investigate the so-called electronic dressed states, a unified quasiparticle resulting from the interaction between electrons in a two-dimensional material with an off-resonance optical dressing field. If the frequency of this field is much larger than all characteristic energies in the system, such as the Fermi energy or bandgap(s), the electronic band structure is affected by radiation so that some important properties of the electron dispersions could be modified in a way desirable for practical applications. For example, a circularly polarized light can be used to vary the bandgap of Dirac materials: it opens a gap in graphene and other metallic and semimetallic lattices, or modifies the magnitude of an existing gap. This will either enhance or reduce a gap, depending on its initial value as well as properties of a host material. Here, we consider gaped dice and Lieb lattices as samples, and put forward a full theoretical model to reveal how these electronic states are deformed by an elliptically-polarized irradiation with a focus on generation and modification of a bandgap.

This study describes the synthesis and characterization of mixed hydrotalcite–organosilica membrane for gas separation. Hydrotalcite exhibits the capability to adsorb carbon dioxide at elevated temperatures. High surface area and favorable coating properties are essential to harness its potential for practical applications. Stable alcohol-based dispersions are needed for thin film applications of mixed membranes containing hydrotalcite. Currently, producing such dispersions without the need for delamination and dispersion agents is a challenging task. This work introduces for the first time a manufacturing approach to overcoming the drawbacks mentioned above. It includes a synthesis of hydrotalcite nanoparticles, followed by agent-free delamination of their layers and final dispersion into alcohol without dispersion agents. Further, the hydrotalcite-derived sorption agent is dispersed in a matrix based on organo-silica gels derived from 1,2-bis(triethoxysilyl)ethane (BTESE). The analytical results indicate that the interconnection between hydrotalcite and BTESE-derived gel occurs via forming a strong hydrogen bonding system between the interlayer species (OH groups, CO32-) of hydrotalcite and oxygen and silanol active gel centers. These findings lay the foundation for applications involving incorporating hydrotalcite-like compounds into silica matrices, ultimately enabling the development of materials with exceptional mass transfer properties. In part 2 of this study, gas separation performance of the organo-silica and the hydrotalcite-like materials and their combined form will be investigated

Exergy analysis evaluates the efficiency of system components by quantifying the rate of entropy generation. In general, the exergy destruction rate or irreversibility rate was directly obtained through the exergy-balance equation. However, this method cannot determine the origin of the component's entropy generation rate, which is a very important factor in system design and improvement. In this study, a thorough energy, exergy thermoeconomic analysis of a proton exchange membrane fuel cell (PEMFC) was performed, providing the heat transfer rate, entropy generation rate and cost loss rate of each component. The irreversibility rate of each component is obtained by the Gouy-Stodolar theorem. Detailed and extensive exergy and thermoeconomic analyses of PEMFC system have determined that water cooling units experience the greatest heat transfer among the components in the studied PEMFC system, resulting in the greatest irreversibility and thus the greatest monetary flow loss.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG) with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. We investigated the antiviral effect of NTP using an in vitro model for HSV-1 cold sores, involving the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. We found NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggest the potential of NTP as a therapeutic agent effective against HSV-1 infection.

Sirtuins, especially SIRT1, play a significant role in the regulation of inflammatory response, autophagy, and cell response to oxidative stress. Since their discovery, sirtuins have been regarded as anti-aging and longevity-promoting enzymes. Sirtuin-regulated processes seem to take part in most prevalent placental pathologies, such as preeclampsia. Furthermore, more and more research studies indicate that SIRT1 may prevent pre-eclampsia development, or at least alleviate its manifestations. Having taken this into consideration, we have made a review of recent studies on the role of sirtuins, especially SIRT1, in the regulation of processes determining normal or abnormal development and functioning of the placenta.

The human interferon-induced transmembrane (IFITM) proteins inhibit the fusion of a broad spectrum of enveloped viruses, both when expressed in target cells and when present in infected cells. Upon expression in infected cells, IFITMs incorporate into progeny virions and reduce their infectivity by a poorly understood mechanism. Since only a few Env glycoproteins are present on HIV-1 particles, and Env clustering has been proposed to be essential for optimal infectivity, we asked if IFITM protein incorporation modulates HIV-1 Env clustering. The incorporation of two members of the IFITM family, IFITM1 and IFITM3, into HIV-1 pseudoviruses verified by Western blotting correlated with a marked reduction of infectivity. Super-resolution imaging of Env distribution on single HIV-1 pseudoviruses did not reveal significant effects of IFITMs on Env clustering. However, IFITM3 markedly reduced the Env processing and incorporation into virions relative to control and IFITM1-containing viruses. These results suggest that IFITM1 and IFITM3 restrict progeny HIV-1 infectivity via distinct mechanisms. We propose that IFITM1 interferes with viral fusion by altering the properties of the viral membrane or Env functionality by means other than disrupting Env clusters, while IFITM3 also targets Env processing and incorporation into progeny virions.

The vascular endothelium is key target for immune, and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that if induced or overexpressed help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of a three human genes in a mouse generated using the multi-cistronic F2A technology. Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5’-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeabil-ity responses. Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic ani-mals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/ monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion mol-ecule levels were observed in transgenic mice in comparison to control after LPS treatment. Fur-thermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as com-pared to LPS-treated control. The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in sev-eral biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation.

Broad-spectrum antifungal drug deployed for topical therapy, specific for onychomycosis, Itraconazole was used as the active pharmaceutical ingredient in a nail lacquer formulation¹. The objective of the study was to optimize an antifungal nail lacquer, which when applied topically onto the dorsal surface of the nail plate would facilitate the transungual penetration of the drug. Itraconazole hydrochloride was synthesized to aid the formulation of the lacquers. The optimization involved comparing four different formulations of 1%w/w Itraconazole nail lacquers containing combinations of penetration enhancers (Papain, Salicylic acid, Urea) based on their ability to facilitate diffusion of the drug through the nail plate over five days. The drug uptake was quantified by extracting the drug from the nail clippings and analyzing it. The tests conducted to account for the quality of the optimized formulation were drug content, spread ability, check for precipitation, and accelerated stability. The results demonstrated that the optimized 1%w/w Itraconazole nail lacquer contained 5%w/w Papain, 5 %w/w Salicylic Acid, and 2.8% w/w Urea. The drug uptake from nail clippings was higher than the literature derived reference MIC90 value for T. Rubrum strain, and the quality of the optimized lacquer was not compromised throughout three weeks [2]. The hypothesis stated that the inclusion of Salicylic acid, Papain, and Urea in an Itraconazole (1%w/w) nail lacquer would have the highest transungual penetration on application to the nail plate. In conclusion, the hypothesis was accepted, and the optimized lacquer passed the drug uptake evaluation and all quality control tests.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

Collatz conjecture states that an integer $n$ reduces to $1$ when certain simple operations are applied to it. Mathematically, the Collatz function is written as $f^k(n) = \frac{3^kn + C}{2^{z}}$, where $z, k, C \geq 1$. Suppose the integer $n$ violates Collatz conjecture by reappearing as $2^in$, where $i \geq 1$, then the equation modifies to $n \left(1 - \frac{3^k}{2^{z}2^i}\right) = \frac{C}{2^{z}2^i}$. The article takes an elementary approach to this problem by calculating the bounds on the values of $\frac{C}{2^{z}2^i}$ and $1 - \frac{3^k}{2^{z}2^i}$. Correspondingly, an upper limit on the integer $n$ is placed that can re-appear in the sequence. The integer $n$ lies in the $(-\infty, 5)$ range, and the limit on the number of odd steps is $k < 3$. Finally, it is shown that no integer chain exists that does not lead to 1.

Hypotrochoidal profile contours have been produced in industrial applications in recent years using twin-spindle processes, and they are considered effective high-quality solutions for positive shaft–hub connections. This study mainly concerns analytical approaches to determine the bending stresses in hypotrochoidal profile shafts. The formulation was developed according to bending principles using the mathematical theory of elasticity and conformal mappings. The loading was further used to investigate the rotating bending behaviour. The stress factors for the classical calculation of maximum bending stresses were also determined for all those profiles presented and compiled in the German standard DIN3689-1 for practical applications. The results were also compared with the corresponding numerical and experimental results, and very good agreement was observed. Additionally, based on previous work, the stress factor was determined for the case of torsional loading to calculate the maximum torsional stresses in the standardised profiles, and the results are listed in a table. This study contributes to the further refinement of the current DIN3689 standard.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that, occasionally, may spread to the central nervous system (CNS), being the most common cause of sporadic encephalitis. One of the main neurovirulence factors of HSV-1 is the protein ICP34.5 that, although initially seemed to be relevant only in neuronal infections, it can also promote viral replication in non-neuronal cells. New ICP34.5 functions have been discovered during the recent years, and some of them have been questioned. This review describes the mechanisms of ICP34.5 to control cellular antiviral responses and debates its most controversial functions. One of the most discussed roles of ICP34.5 is autophagy inhibition. Although autophagy is considered a defense mechanism against viral infections, current evidence suggests that this antiviral function is only one side of the coin. Different types of autophagic pathways interact with HSV-1 impairing or enhancing the infection, and both the virus and the host cell modulate these pathways to tip the scales in its favor. In this review, we will summarize the recent progress on the interplay between autophagy and HSV-1, focusing on the intricate role of ICP34.5 in the modulation of this pathway to gain the battle against cellular defenses.

HIV-1 Nef is a multifunctional protein with well-known lethal properties. HIV infects various cells from the brain compartment and expressed nef is responsible for developing neuropathogenic potential. HIV-infected glial cells express nefvirotoxinand stimulate the cascade of various pathways to activate uninfected cells to release neurotoxic elements damaging cells themselves. A lot of genetic variabilities of this protein have been reported from patients with HIV-associated neurocognitive disorders. To determine the neurotoxic potential of subtype-specific nef plasmids and nef plasmids of clinical samples with and without HAND were transfected in normal human astrocytes (NHA) and monocyte-derived macrophages (MDM) using nef-pCMV-HA plasmid constructs. Supernatants from subtype-specific Nef plasmids indicated the upregulation of proinflammatory cytokines. The induced expression might be due to the nef genetic variability or variations in the transfection efficiency and expression levels of nef.The mRNA expression of IL-6, IP-10, and TNF-α indicated upregulation of 5.0-fold in NHA and 3-fold in MDM with respect to empty vector control transfection. Further, the kynurenine metabolites were also assessed from culture supernatants of NHA and MDM indicating the upregulation of IDO and KYNU in NHA by 3.0-fold and 3.2-fold in MDM.The expression levels of nef and cytokines at the translational level were confirmed by western blotting and bio-plex Pro cytokine estimation assay respectively along with controls expressing green fluorescent protein (GFP).The oxidative stress was also found to be elevated as compared to control cells as determined by the estimation of nitric oxide from the culture supernatant to confirm the neurotoxic potential of HIV nef plasmids. The downregulation in the levels of cytokines, as well as kynurenine metabolites, was observed in culture supernatants after blocking the expression of nef using HIV nef siRNA. Phylogenetic analysis of Nef sequences indicated subtype C predominance except one sequence showing the partial sequence of HIV-1 subtype B sequence forming BC recombinantThe upregulation in the cytokine and pathway-specific metabolites might be linked with the neurotoxic potential of HIV-1 Nef leading to neuropathogenesis. In conclusion, the variation in the transfection efficiency, nef expression levels, and the genetic variability of Nef might be responsible for upregulating the expression levels of cytokines and kynurenine metabolites in astrocytes and MDM.

Ho Chi Minh City (HCMC), the most crowded city and economic hub of Viet Nam, has been experiencing land subsidence over the past decades. This effort aims to contribute the spatial distribution of subsidence in HCMC in its horizontal and vertical components using synthetic aperture radar interferometry (InSAR) time series. To this purpose, an advanced Persistent Scatterers and Distributed Scatterers (PSDS) InSAR technique was applied to two European Space Agency (ESA) Sentinel-1 datasets consisting of 96 ascending and 202 descending images, acquired from 2014 to 2020 over the HCMC area. A time series of 33 COSMO-SkyMed ascending images was also used for comparison. The combination of ascending and descending satellite passes is used to decompose the light of sight velocities into horizontal east-west and vertical components. Taking into account the presence of east-west horizontal motion, our findings indicate that the accuracy of the decomposed vertical velocity can be improved by up to 3 mm/year for Sentinel-1 data. The obtained results revealed that subsidence is most pronounced in the areas along the Sai Gon River, in the northwest-southeast axis, and in the southwest of the city, with a maximum value of 80 mm/yr, which is in accordance with the findings of the literature. The amplitude of east-west horizontal velocities is relatively small and large-scale eastward movement can be observed in the west of the city at a rate of 3-5 mm/yr. This confirmed that the displacement in Ho Chi Minh City area is mainly vertical downward. Together, these results reinforced the remarkable suitability of ESA's SAR Sentinel-1 for subsidence applications, even for non-European countries such as Vietnam and Southeast Asia.

Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extra-mitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP-synthase (E55A mutation), indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca2+ handling, which resulted in sarcoplasmic reticulum Ca2+ overloading. The effects of IF1 on Ca2+ handling were associated with the cytosolic activation of CaMKII and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF-1 induced pathological hypertrophy. Conclusions IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase independent, role for IF1 in mitochondrial Ca2+ handling and mitochondrial- to nuclear crosstalk involving CaMKII.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings of miRNAs and mRNAs expressed in CD4+ T-lymphocytes upon HIV-1 infection. Our results reveal significant alterations of miRNAs and mRNAs expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T-cells. Addition of miRNA-26a mimics to CD4+ T-cells reduces CD59 at both mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking-out CD59 in CD4+ T-cells renders both HIV-1 infected cells and progeny virions more prone to antibody-dependent CML (ADCML). Addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction of CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.

Clopidogrel; a prescription drug to reduce ischemic events in cardiovascular patients; has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU); PON1 abundance by western blotting and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p> 0.05). However; a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Quite a number of cottonseed varieties are existed. The seeds of each variety produce a different amount of gossypol as a natural toxic compound. The increased interest in this natural product and its toxic effects were enhanced the demand for establishing simple silica-gel-based methods for its isolation, purification, and characterization. Historically, silica gel plays a significant role in isolation and purification of many different natural products. Silica gel is variants and can intro-duce a lab, simple tool for tracking a compound in certain plants during its purification process. In this study, gossypol was isolated and purified in the form of yellow crystals as gossypol acetic ac-id. Several methods and tools were used for its characterization including TLC, preparative TLC, silica gel column, UV/IR spectrophotometer and HPLC (Robust spherical silica gel). A compara-tive study between its amounts in both Egyptian and Chinese varieties were performed. Under the experimental condition, the Egyptian cottonseeds contain 8.705 gm/kg, while the Chinese contains 5.395 gm/kg. Thin Layer Chromatography (TLC) had been flourished the science of the phytochemistry and still popular till nowadays and is recommended for fast, accurate, and inex-pensive evaluation and quantification of gossypol. It is recommended to isolate and purify gossy-pol as gossypol acetic acid using optimized combined methods used in this study. Using Silica gel different protocols will assist and facilitate the parallel comparison and save the compact column from any unexpected contaminants during the purification steps. During each step the silica gel itself could be simply removed by paper filtration.

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

Recent advances in satellite technology have brought enormous potential to ecosystem mapping, which is one of the fundamental components of environmental studies. In this paper, a Random Forest classifier is applied for the strict assessment of the efficiency of ecosystem mapping through a detailed comparative analysis between combined Sentinel-1 and Sentinel-2 data and stand-alone Sentinel-2 imagery over three priority ecosystems, including wetlands, riverine areas, and mangroves in Bangladesh. The collocated images, based on the integration of Sentinel-1 data with Sentinel-2 data, would do better than Sentinel-2 imagery alone over various ecosystems. Particularly, in this study, attention focused on the Hakaluki Haor area for the wetlands, the Padma-Jamuna River confluence for the riverine ecosystem, and the Sundarban forest for mangroves. By leveraging Synthetic Aperture Radar (SAR) data in C-band dual-polarization from Sentinel-1 and four spectral bands (blue, green, red, and near-infrared) from Sentinel-2, the study analyzes imagery from December 2022 to February 2023. A 5% cloud masking filter is applied to optical data to enhance accuracy. In this methodology, 70% of the total signature values are used for training the classification model and the remaining 30% for testing. It can be noticed from the results that with the use of fused data, remarkably high accuracy in classification has been improved, such as overall accuracies of 94.17% for mangroves, 87.30% for riverine, and 85.96% for wetland ecosystems. In contrast, the use of singular Sentinel-2 imagery yields lower accuracies of 91.56%, 85.21%, and 82.51% for the respective ecosystems. The integration of radar data is shown to provide critical information, especially in environments with dense vegetation or cloud cover, where optical data alone may be insufficient. The findings of this study underline the limitations of relying on Sentinel-2 imagery to capture complex details of diverse ecosystems and highlight the need to include Sentinel-1 data for a more holistic analysis. This fusion allows improved accuracy to be achieved, which not only brings in more depth of ecological knowledge but also underpins more effective conservation strategies.

Reactive oxygen species (ROS) are produced during cellular metabolism and in response to environmental stress. While low levels of ROS play essential physiological roles, excess ROS can damage cellular components, leading to cell death or transformation. ROS can also regulate protein interactions in cancer cells, thereby affecting processes such as cell growth, migration, and angiogenesis. Dysregulated interactions occur via various mechanisms, including amino acid modifications, conformational changes, and alterations in complex stability. Understanding ROS-mediated changes in protein interactions is crucial for targeted cancer therapies. In this review, we examine the role that ROS mechanisms in regulating pathways through protein-protein interactions.

Objectives: Epidemiologic and experimental animal studies have shown that stress can alter tumor growth and that adrenergic fibers from the sympathetic nervous system, acting through stromal β2-adrenergic receptors, promote tumor cell survival during the initial phases of cancer development. Recent epidemiological data suggest that beta blocker intake improves survival of prostate cancer patients. Methods: Signaling mediated by β-adrenergic receptors promotes neuroendocrine differentiation in prostate cancer cell line. Although neuroendocrine cells are a minor population in the epithelial compartment of normal prostate glands, the population of neuroendocrine-like cells that express markers such as SYN, Bcl-2, Dll-3, and AMACR correlates with cancer progression, androgen-independent state, and poor prognosis in prostate cancer patients. As recent studies show that an increase in neuroendocrine cell density occurs before development of benign prostatic hyperplasia (BPH), a non-lethal disease affecting the transition zone, in hypertensive rats, we investigated whether neuroendocrine differentiation is associated with BPH. Results: Our results showed that isobutyl-methyl-xanthine and forskolin leading to sustained activation of the cAMP/PKA pathway led to an increase in neuroendocrine differentiation markers in BPH-1 cell line. Similar results were observed by combining the β-adrenergic receptors agonist isoproterenol with forskolin. These treatments reduced BPH-1 cell proliferation rates by 40% and 60%, respectively. Effects on neuroendocrine markers expression and cell proliferation were fully reversed by the β2 blocker carvedilol. Conclusion: These data suggest that β-adrenergic receptors are linked to the development of neuroendocrine-like cells in BPH. As 20% of the prostate cancer tumors occur in this zone, this observation warrants further investigation.

Several studies have shown promising treatments for type 1 diabetes mellitus (T1DM) using developing gene therapy methods. This review article focuses on summarizing possible new treatment options and outlining their pros and cons, since there is no cure for T1DM as of yet. New treatments involve islet and stem cell transplantation, genetic vaccination, and immunological precursor cell-mediated therapy. Since most of these methods are still in their early stages, efficacy in human trials of this type of treatment is still largely unknown, however, researchers are hopeful after numerous successes in trials with non-obese diabetic (NOD) mice.

Sepsis, characterized by a dysregulated systemic inflammatory response to infection, remains a significant global health burden, despite substantial advancements in its treatment. An understanding of the underlying mechanisms driving sepsis is crucial for the development of targeted therapeutic strategies. Silent information regulator 1 (SIRT1), a member of the class III histone deacetylases, plays a pivotal role in regulating gene expression by catalyzing the deacetylation of lysine residues on non-histone and histone proteins. With the advancement of sepsis research, SIRT1 has been shown to exert significant anti-inflammatory, anti-oxidative, anti-apoptotic, and metabolic regulatory effects, positioning it as a potential therapeutic target for sepsis. This article reviews the latest progress on research into the signaling pathways modulated by SIRT1 in sepsis and its associated regulatory mechanisms to further elucidate the pathogenesis of sepsis and assist in guiding clinical treatment.

The increasing concern regarding climate change continues to motivate research in the Arctic. Within the delicate cycle of the cryosphere, leads are an important kinematic feature that regulates heat balances and gaseous exchanges in the Arctic. Therefore, it is necessary to quantify the genesis of leads over time to identify when and where changes are occurring. The use of learning techniques is one such tool that is used to identify the characteristics of seasonal ice variability. This paper utilizes the Sentinel-1 RADAR imagery with a support vector machine learning scheme through Google Earth Engine to classify lead types in the Beaufort Sea.

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. Our study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion, in an autophagy-dependent manner. Intriguingly, THSD1-mediated autophagy activation operates independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than serving as a global regulator of nutrient and energy status. Interestingly, THSD1 negatively regulates Beclin 1, a central autophagy regulator, at FAs through interactions with focal adhesion kinase (FAK). The loss of THSD1 diminishes FAK activity, consequently relieving its inhibitory phosphorylation on Beclin 1. This, in turn, promotes the complex formation between Beclin 1 and ATG14, a critical event for the activation of the autophagy cascade. In summary, our findings identify THSD1 as a novel regulator of autophagy that degrades FAs in brain endothelial cells. This underscores the distinctive nature of THSD1-mediated, cargo-directed autophagy and its potential relevance to vascular diseases due to the loss of endothelial FAs. Investigating the underlying mechanisms of THSD1-mediated pathways holds promise for discovering novel therapeutic targets in vascular diseases.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining &gt;10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Background: Implantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells, platelets, and circulating leukocytes. The aim of this study was to mask endovascu-lar stents with peptides imitating CD31, to mimic the device's surface to resemble that of a healthy vascular endothelium. Methods: Peptide design relied on established trans-homophilic sequences found within domains 1 and 2 of CD31. Subsequently, synthetic peptides were immobilized onto flat CoCr and nitinol discs and their impact on the primary human arterial endothelial cell phenotype was evaluated in vitro. Following this, clinical-grade CoCr and nitinol endovascular devices were coated with one of the peptides that demonstrated the capability to induce a pro-physiologic endothelial phenotype, implanted in the arteries of rabbits, and compared to un-coated controls. Results: Membrane-distal CD31 domains 1 and 2 peptides exhibited a distinct capability to foster a healthy endothelial phenotype in vitro. By day 7 post-aortic implantation, CoCr stents were evenly covered by whole-some endothelial cells, devoid of thrombo-inflammatory signs, in contrast to both bare metal and drug-eluting stents. At day 60, nitinol-coated flow diverters demonstrated enhanced performance in comparison to the control groups for excluding experimental carotid aneurysms, facilitating the formation of a seamless "neo-arterial" wall. Conclusion: Membrane-distal CD31 biomimetic peptides effectively camouflage the device surface, prevent-ing local reactions and promoting rapid and seamless endovascular integration.

Phosphorus (P) is an essential plant macronutrient; however, its availability is often limited in soils. Plants have evolved complex mechanisms for efficient phosphate (Pi) absorption, which are responsive to changes in external and internal Pi concentration, and orchestrated through local and systemic responses. To explore these systemic Pi responses, here, we identified AtMYB44 as a phloem-mobile mRNA, an Arabidopsis homolog of Cucumis sativus MYB44, that is responsive to the Pi-starvation stress. qRT-PCR assays revealed that AtMYB44 was up-regulated and expressed in both shoot and root in response to Pi-starvation stress. The atmyb44 mutant displayed higher shoot and root biomass, compared to wild-type plants, under Pi-starvation conditions. Interestingly, the expression of PHOSPHATE TRANSPORTER1;2 (PHT1;2) and PHT1;4 was enhanced in atmyb44 in response to a Pi-starvation treatment. A split-root assay showed that AtMYB44 expression was systemically regulated, under Pi-starvation conditions and, in atmyb44, systemic controls on PHT1;2 and PHT1;4 expression were moderately disrupted. Heterografting assays confirmed graft transmission of AtMYB44 transcripts, and PHT1;2 and PHT1;4 expression was decreased in heterografted atmyb44 rootstocks. Taken together, our findings support the hypothesis that mobile AtMYB44 mRNA serves as a long-distance Pi response signal, which negatively regulates Pi transport and utilization in Arabidopsis.

Irrigation is one of key agricultural management practices of crop cultivation in the world. Irrigation practice is traceable on satellite image. Most irrigated area mapping methods were developed based on time series of NDVI or back scatter coefficient within the growing season. However, it found the winter irrigation out of growing season is also dominating in north China. This kind of irrigation aims to increase the soil moisture for coping with spring drought, and also reduce the wind erosion with the wet soil in the field surface as the strong wind happens in spring. This study developed a remote sensing-based classification approach to identify irrigated fields with Radom Forest algorithm out of growing season. The results showed that the mean of the highest accuracies of 7 RF models was 94.9% and the mean of the averaged accuracies of 7 RF models was 94.1%; the overall accuracy for all 7 outputs was in the range of 86.8-92.5%, Kappa in the range of 84.0-91.0% and F-1 score in the range of 82.1-90.1%. These results showed that the classification was acceptable and not over performed as the accuracies of all classified images were lower than the models. This study also found that irrigation started to apply in early November and irrigated fields were increased and suspended in December and January due to freeze. The newly irrigated fields were found again in March and April when the temperature goes up above zero degree. The area of irrigated fields in the study area were increasing over time with sizes of 98.6, 166.9, 208.0, 292.8, 538.0, 623.1, 653.8 km2 from December to April, accounting for 6.1%, 10.4%, 12.9%, 18.2%, 33.4%, 38.7%, and 40.6% of the total irrigatable land in the study area, respectively.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

Vessel co-option correlates with resistance against anti-angiogenic agents and chemotherapy in colorectal cancer liver metastasis (CRCLM). We previously identified higher intensity of neutrophils in the tumour microenvironment of vessel co-opting CRCLM lesions compared to their angiogenic counterparts. Herein, we demonstrated that over 50% of the neutrophils in vessel co-opting lesions are expressing pro-apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1). Our previous publications suggested upregulation of transforming growth factor-beta (TGFβ1) in the microenvironment of vessel co-option CRCLM. Therefore, we examined the effect of TGFβ1 on the expression of cleaved caspase-3 and PARP-1 in neutrophils in vitro. Significantly, we noticed the upregulation of pro-apoptotic markers upon exposure to TGFβ1. This finding might pave the way to determine the role of neutrophils in developing vessel co-option in CRCLM in the future.

This study focuses on one of the most famous open problems in mathematics, namely the Collatz conjecture. The Collatz conjecture or 3x + 1 Problem is perhaps today's most enigmatic unsolved mathematical problem. It is named after Lothar Collatz, who rst proposed it in 1937. It may be stated as as follow: Take any positive integer n. If n is even then divide it by 2, else do \triple plus one" and get 3n + 1. The conjecture is that this process will eventually reach the number 1, regardless of which positive integer is chosen initially. In this paper, we present a simple proof for the Collatz conjecture.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

The human immunodeficiency virus 1 (HIV-1) viral protease (PR) is one of the most studied viral enzymes, and approval of drugs targeting its catalytic activity opened the door to the develop-ment of highly active antiretroviral therapy (HAART). Despite the fact that its crucial role in viri-on maturation is well characterized, an increasing body of research is starting to focus on its abil-ity to cleave host cell proteins, based on recent advances in proteomics and genomics technologies. Such findings are apparently in contrast with the dogma of HIV-1 PR activity being restricted to the interior of nascent virions, and suggest catalytic activity within the host cell environment. Given the limited amount of PR present in the virion at the time of infection, it is tempting to specu-late that such events mainly occur during viral late gene expression, mediated by newly synthe-sized Gag-Pol polyprotein precursors, rather than at a very early stage of infection, before pro-viral integration. Among cellular targets of HIV-1 PR, three major clusters can be identified: pro-teins involved in viral and cellular translation, those controlling cell survival, and restriction fac-tors responsible for innate/intrinsic antiviral responses. Indeed, by cleaving host cell translation initiation factors HIV-1 PR can impair cap-dependent translation, thus promoting IRES-mediated translation of late viral transcripts and viral production, while by targeting several apoptotic fac-tors it modulates cell survival, thus promoting immune evasion and viral dissemination. Addi-tionally, HIV-1 PR counteracts restriction factors incorporated in the virion that would otherwise interfere with nascent virus vitality. Thus, HIV-1 PR appears to modulate host cell function at dif-ferent times and locations during its life cycle, to ensure efficient viral persistency and propaga-tion. This kind of PR-mediated host cell modulation is found in a plethora of different viruses and HIV-1 is no exception, and although we are far from having a complete picture, it is clear that the PR has a multifaceted role in interfering with host machineries to better suit viral replication, and is a field that needs to be explored further.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

Obesity is characterized by chronic low-grade inflammation. Caveolin-1 (CAV1), a structural and functional protein found in adipose tissues (AT), is augmented in obese individuals. We aimed to define the inflammatory mediators that influence CAV1 gene regulation and associated mechanism in obesity. Using subcutaneous AT from 27 (7 lean/20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). CAV1 gene expression was associated with that of proinflammatory cytokines/chemokines, and their cognate receptor (r ≥ 0.447, p ≤ 0.030) but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-kB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and TNF-α signaling pathway is interesting and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

In this study, a structural profiling of equid alphaherpesvirus 1 (EHV-1) transcriptome was carried out using next-generation (Illumina) and third-generation (Oxford Nanopore Technologies) sequencing platforms. We annotated the canonical mRNA molecules and their isoforms, including transcript start and end site isoforms, and splice variants. Additionally, a number of putative 5′-truncated mRNAs containing shorter in-frame ORFs were detected. We also demonstrated that EHV-1 produces a high number of non-coding transcripts, including antisense and intergenic RNAs. One of the most remarkable features of the EHV-1 is the generation of abundant fusion transcripts some of which encoding chimeric polypeptides. We observed a higher number of splicing and transcriptional overlaps than in related viruses. Additionally, we found that many upstream genes of tandem gene clusters have their own transcript end sites (TESs) besides the co-terminal TESs, which is rare in other alphaherpesviruses. We show here that the replication origins (OriS and OriL) of the virus are co-localized with promoter sequences and overlap with specific RNA molecules. Furthermore, we discovered a novel non-coding RNA (designated as NOIR) that overlaps the 5′-ends of the longer transcript variants encoded by the two main transactivator genes ORF64 and 65 bracketing the OriL. These all suggest the existence of a central regulatory system which controls the genome-wide transcription and the replication through a mechanism based on the interference between the machineries carrying out the synthesis of DNA and RNA.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treat-ment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provided limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory conditions and experi-mental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model of human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, including podocyte loss. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by targeting NOTCH signaling pathway. JQ1 inhibited the gene expression of the NOTCH effec-tors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis.

Chronology unprotected mechanisms are considered with a very low gravitational polarization to make the wormhole traversal with positive energy density everywhere. No need of exotic matter has been considered with the assumption of the Einstein-Dirac-Maxwell Fields, encountering above the non-zero stress-energy-momentum tensor through spacelike hypersurfaces by a hyperbolic coordinate shift.

Phase synchronization is one of the key issues that must be addressed in the bistatic synthetic aperture radar (BiSAR) system. LuTan-1 is an innovative L-band spaceborne BiSAR mission of China. An advanced synchronization scheme is used in the LuTan-1 system. The synchronization pulses are exchanged immediately after the ending time of the radar echo receiving window and before the starting time of the next pulse repetition interval. Therefore, it can not interrupt the normal SAR data acquisition, further improving synchronization frequency and avoiding the data missing effect. In order to accurately monitor system malfunctions and compensate for the phase synchronization errors introduced by hardware system, an innovative internal calibration strategy is designed and employed in the LuTan-1 mission. The test data acquired from the ground validation system of LuTan-1 are used to demonstrate the feasibility of the proposed scheme. The results validate the effectiveness of the proposed scheme and prove the promise for its future application in LuTan-1.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

In present study, the effect of Inonotus Obliquus extracts used in traditional medicine was investigated on the expression of matrix metalloproteinases-1 (MMP-1) in the normal human dermal fibroblasts. As shown our results, extracts of Inonotus Obliquus decreased MMP1 expression in oxidative stress-exposed normal human dermal fibroblasts. Additionally, Inonotus Obliquus extracts decreased AP-1 transcriptional activity and phospho-JNK in oxidative stress exposed normal human dermal fibroblasts. The results suggest that Inonotus Obliquus extracts decreased MMP1 expression using decreasing AP-1 transcriptional activity and phospho-JNK. Therefore, Inonotus Obliquus extracts has potential to reduce formation of wrinkle and to use as a cosmetic ingredient.

Purinergic receptors are inflammatory mediators activated by extracellular nucleotides released by dying or injured cells. Several studies have described an important role for these receptors in HIV-1 entry, particularly regarding their activity on HIV-1 viral membrane fusion. Several reports identify purinergic receptor antagonists that inhibit HIV-1 membrane fusion; these drugs are suspected to act through antagonizing Env-chemokine receptor interactions. They also appear to abrogate activity of downstream mediators that potentiate activation of the NLRP3 inflammasome pathway. Here we review the literature on purinergic receptors, the drugs that inhibit their function, and the evidence implicating these receptors in HIV-1 entry.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Predicting how a genetic change affects a given character is a major challenge in biology, and being able to tackle this problem relies on our ability to develop realistic models of gene networks. However, such models are rarely tractable mathematically. In this paper, we propose a mathematical analysis of the sigmoid variant of the Wagner gene-network model. By considering the simplest case, that is, one unique self-regulating gene, we show that numerical simulations are not the only tool available to study such models: theoretical studies can be done too, by mathematical analysis of discrete dynamical systems. It is first shown that the particular sigmoid function can be theoretically investigated. Secondly, we provide an illustration on how to apply such investigations in the case of the dynamical system representing the one self-regulating gene.

Introduction: A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). Material and Methods: The study analysed articles published in JCR journals from 2019 to 2024, including retrospective, prospective, case-control, or cross-sectional studies. It combined MESH and free terms for "Epileptogenesis" and "Neuroinflammation" and included searches for biomarkers previously reported in narrative reviews. Results: The study analysed 243 articles related to epileptogenesis and neuroinflammation, with 356 from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 52 evaluated by authors. 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. This systematic review provides acceptable support for five biomarkers: TNF-a and some of its soluble receptors (sTNFr2), HMGB1 and TLR-4, CCL2 and IL-33. Discussions: Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control levels of epileptic patients. Their value will be better defined by future studies.

Chronic kidney disease (CKD) bears a heavy burden on patients and the health care system as whole. The incidence of CKD has been increasing in the Arab world over the years due to increases in Diabetes and hypertension which are the most prominent causes of CKD. Syrians are at higher risk for diabetes and hypertension due to the crisis that the country has been going through. 297 patients’ charts were examined in the kidney surgical hospital in Damascus Syria to determine risk factors for CKD, prevalence of diabetes among them and its associating demographic factors along with changes in serum creatinine, urea, fasting blood glucose levels and MDRD score among diabetic CKD patients. 64.6% of patients were above 50, 61.6% were males and 35.4% were diabetic. Patients with diabetes had lower creatinine levels upon admission than non-diabetics. The correlation between fasting blood glucose level and serum creatinine, urea and MDRD was not statistically significant. This paper shows that the prevalence of diabetes among CKD patients is similar in Syrians to the rest of the world despite the increase of diabetes incidence.

Background and objectives: TSC1 is a crucial component of the mTOR pathway, impacting cell growth, proliferation, and autophagy, while TSC2 is a tumor suppressor gene that regulates cell growth and is associated with the mTOR signaling pathway. In the present study, we analyzed TSC1 and TSC2 mRNA expression levels in rectal cancer, and evaluated the clinicopathological and prognostic characteristics of TSC1 and TSC2. Materials and Methods: TSC1 and TSC2 mRNA expression was examined in various cancer types. We further evaluated survival to determine the prognostic significance of TSC1 and TSC2 mRNA in CRC using The Cancer Genome Atlas (TCGA) data. Results: The study focused on rectal cancer, as it exhibited the most promising results. The patients were split into two subgroups, each comprising 50% of the total, based on the TSC gene expression levels. This division was made to assess the clinical characteristics associated with the expression of TSC1 and TSC2 genes. In the study, lower TSC1 expression was linked to venous invasion in rectal cancer patients, and there was also a related trend with lymphatic invasion, although it didn't reach statistical significance. Lower TSC2 expression was observed in younger patients and had some associations with sex and M stage, but these correlations were not statistically significant. When it came to survival analysis, TSC1 expression did not significantly impact overall survival, while higher TSC2 expression was associated with a poorer prognosis in rectal cancer. To enhance our comprehension, additional research, especially in larger case studies, is needed to explore the molecular mechanisms and clinical characteristics of TSC genes in colorectal cancer.

Satellite Crop Detection technologies are focused on detection of different types of crops on the field in the early stage before harvesting. Crop detection is usually done on a time series of satellite data by classification of the desired fields. Currently, data obtained from Remote Sensing (RS) are used to solve tasks related to the identification of the type of agricultural crops, also modern technologies using AI methods are desired in the postprocessing part. In this challenge Sentinel-1 and Sentinel-2 time series data were used due to their periodic availability. Our focus was to develop methodology for classification of time series of Sentinel 2 and Sentinel 1 data and compare how accuracy of classification can be increased, but also how to guarantee availability of data. We analyse phenology of single crops and on the basis of this analysis we started to provide crop classification. Original crop classifications were made from Enhanced Vegetation Index (EVI) layers made from Sentinel-2 time-series data and then we added also . To increase accuracy we also integrate into the process parcel borders and provide classification of fields..

Mapping forest extent and forest cover classification are important for the assessment of forest resources in socio-economic as well as ecological terms. Novel developments in the availability of remotely sensed data, computational resources, and advances in areas of statistical learning have enabled fusion of multi-sensor data, often yielding superior classification results. Most former studies of nemoral forests fusing multi-sensor and multi-temporal data have been limited in spatial extent and typically to a simple classification of landscapes into major land cover classes. We hypothesize that multi-temporal, multi-censor data will have a specific strength in further classification of nemoral forest landscapes owing to the distinct seasonal patterns of the phenology of broadleaves. This study aimed to classify the Danish landscape into forest/non-forest and further into forest types (broadleaved/coniferous) and species groups, using a cloud-based approach based on multi-temporal Sentinel 1 and 2 data and machine learning (random forest) trained with National Forest Inventory (NFI) data. Mapping of non-forest and forest resulted in producer accuracies of 99% and 90 %, respectively. The mapping of forest types (broadleaf and conifer) within the forested area resulted in producer accuracies of 95% for conifer and 96% for broadleaf forest. Tree species groups were classified with producer accuracies ranging 34-74%. Species groups with coniferous species were the least confused whereas the broadleaf groups, especially Oak, had higher error rates. The results are applied in Danish National accounting of greenhouse gas emissions from forests, resource assessment and assessment of forest biodiversity potentials.

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

: AliCPT-1 is the first Cosmic Microwave Background (CMB) experiment in China, dedicated to achieve accurate measurements of B-mode polarization. Situated in Ali of Tibet, China, this telescope is currently undergoing deployment and will operate in two frequency bands centered at 90 and 150 GHz. The Far-Field Flat Mirror（FFF）is a calibration device of AliCPT-1 telescope for far-field beam mapping. The design of FFF is optimized for easy assembly and adjustment. Meteorological station data reveals that the maximum wind speed near FFF is 17.5 m/s, while the maximum wind speed on the windward side is 8 m/s. The wind pressure on FFF was analysed using a maximum wind speed of 17.5m/s as the input condition, based on the fluid-structure coupling method in ANSYS. The results demonstrate that it is safe and reliable when withstanding combined gravity and wind pressure loads. The torque on the mount is within the motor rated torque. The flatness of the FFF reflective surface can be adjusted to an RMS value of 0.05 mm when taken into account the effect of gravity and assembly accuracy. The deformation caused by the maximum wind loads is approximately 0.0587 mm under the protection of wind-proof wall. The combined deformation is 0.077 mm in RMS value combining the two influences, which is less than 1/20 of wavelength. The FFF mirror assembly is stable and precisely for telescope calibration.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phag-es). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being pro-teinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacte-ria are highly diverse and, for the majority, remain poorly understood. Their long, flexible and multi-domain encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined by X-ray crystallography.

ABSTRACT: Objectives: Oncostatin M (OSM), a member of the interleukin (IL)-6 family of cytokines, is known to elicit pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is not yet known how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in sinonasal specimens of CRS patients, and we compared the results with a panel of inflammatory cytokine levels and clinical features. Materials and Methods: We classified CRS patients as eosinophilic (ECRS, n=36) or non-eosinophilic (non-ECRS, n=35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, and we compared their cases with those of 68 non-CRS subjects. We also examined stimulatory effects of OSM on the expression levels of cytokine receptors by using the human bronchial epithelium cell line BEAS-2B. Results: An RT-PCR showed that the OSM mRNA levels were significantly increased in the ethmoid sinus mucosa of the CRS patients. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMR-β, IL-1R1, and IL-13Ra mRNA levels. Conclusions: Our findings indicate that OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

This study aimed to identify and differentiate the factors that may affect the incidence of temporomandibular joint (TMJ) dysfunction in children with type 1 diabetes. We analyzed the TMJ symptoms, clinical and laboratory parameters of type 1 diabetes in a cohort of 101 consecutive patients. The participants were evaluated regarding the presence of pain in the masticatory muscles, TMJ sounds, mouth opening, maximum mouth opening, lateral and protrusive excursions, and Fonseca scores. The overall cohort showed a mean Fonseca score of 20 ± 13.89, referred to mild TMJ dysfunction. Of patients, 34.65% presented at least one clinical symptom and were defined as having dysfunction. The most frequently recorded symptom was TMJ sounds, presented in 16.8% of children. In subjects with dysfunction compared to those without dysfunction, a significant difference was found at height standard deviation scores, Fonseca scores and maximum mouth opening (p&lt;0.001). HbA1c levels, diabetes duration, age and gender did not reveal any significant differences between the patients with and without dysfunction. Type 1 diabetes is often associated with limited mouth opening and mild TMJ dysfunction. This dysfunction may reflect a more chronic condition and possibly exceeds the prevalence of cheiroartropathy. This study could be a starting point towards enhancing our understanding of clinically evident TMJ involvement in type 1 diabetes.

Lead-based ternary chalcogenide thin films of the (PbTe)1-x(PbS)x system were obtained by plasma-enhanced chemical vapor deposition technique (PECVD) under conditions of a nonequilibrium low-temperature argon plasma of an RF discharge (40.68 MHz) at a reduced pressure (0.01 Torr). High-purity elements were directly used as starting materials – Pb, S and Te. Plasma-chemical synthesis was carried out on the surface of of c-sapphire and silicon substrate. The physicochemical properties of the films were studied by various analytical methods. The dependence of the Seebeck coefficient, resistivity, and power factor on the structural properties and composition has been studied. The thermoelectric characteristics were found to be dependent on the film composition. Upon the selection of optimal sulfur concentration one can increase the power factor as compared to single phase PbS ot PbTe films.

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Surface soil moisture (SSM) is a significant factor affecting crop growth. This paper presents a method for retrieving SSM over wheat-covered areas using synergy dual-polarization C-band Sentinel-1 synthetic aperture radar and Sentinel-2 optical data. Firstly, a modified water cloud model (WCM) was proposed to remove the influence of vegetation from the backscattering coefficient of the radar data. The vegetation fraction was then introduced in this WCM, and the vegetation water content (VWC) was calculated using multiple linear regression model. Subsequently, the support vector regression technique was used to retrieve the SSM. This approach was validated using in-situ measurements of the wheat field in Hebi, in the north of Henan Province. The key findings of this study are as follows: (1) Based on vegetation indices obtained from Sentinel-2; the proposed VWC estimation model can effectively eliminate the influence of vegetation; (2) compared with vertical transmit and horizontal receive polarization, vertical transmit and vertical receive polarization is better for detecting changes in SSM at different growth stages of wheat; and, (3) the validation results indicated that the proposed approach, based on Sentinel-1 and Sentinel-2 data, successfully retrieved SSM in the study area.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared 15 SCs and their derivatives (tetrahydrocannabinol [THC], naphthoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.

The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral Integrase (IN) enzyme catalyses integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of Integrase Strand Transfer Inhibitors (INSTIs). In this study, we applied computational methods of molecular modelling and docking to analyse the effect of NOPs on the full-length IN structure and INSTI binding. We identified 16 NOPs within the Cameroonian derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any effect on INSTI binding. INSTIs displayed similar binding affinities to each IN structure. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment naïve populations. This study supports the use of second-generation INSTI DTG as part of first-line combination antiretroviral therapy (cART) regimens, due to DTG possessing a stronger genetic barrier to the emergence of drug resistance.

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

The maintenance of high quality standards for prolonging shelf life of fruit and maintaining sensory and nutritional quality is a priority the horticultural products. The aim of this work was to test the effectiveness of a single treatment of edible coating based on Aloe arborescens and a combined treatment of 1-Methylcycyclopropene and edible coating to prolong the shelf-life of "Settembrina" white flesh peach fruit. White flesh peach fruit were harvested at the commercial ripening stage and treated with edible coating (EC) or 1-MCP +EC and stored for 28 days at 1°C. After 7, 14, 21 and 28 days fruits were removed from cold storage, transferred at 20°C and then analyzed immediately (cold out) and after 6 days (shelf life) to evaluate the combined effect of cold storage and room temperature. Weight loss, physical, chemical and sensory parameters were measured. Fruit treated with EC and 1-MCP +EC kept their marketing values better than CTR after 14 days of storage and 6 days of simulated shelf life, in terms of flesh firmness, total soluble solids and titratable acidity as well as sensory parameters. After 21 days of storage, all treatments showed a deterioration of the quality parameters. The single and combined application of Aloe-based coating (with 1-MCP) slowed down the maturation processes of the fruit, limited the weight loss and preserved its organoleptic characteristics.

Interaction of an electromagnetic field with matter in a laser cavity without the assumption of a fixed direction of the transverse electric field, described by the two-level Maxwell-Bloch equations, is studied. By using a perturbative nonlinear analysis, performed near the laser threshold, we report on the derivation of the laser (3+1)D vectorial complex cubic-quintic complex Ginzburg-Landau equation. Furthermore, we study the modulational instability of the plane waves both theoretically using the linear stability analysis, and numerically, using direct simulations via the split-step Fourier method. The linear theory predicts instability for any amplitude of the primary waves. Our numerical simulations confirm the theoretical predictions of the linear theory as well as the threshold of the amplitude of perturbations. The system understudy shows a deep dependence on the laser cavity parameters, for which there appear wave patterns in accordance with the predictions from the gain spectrum.

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells that has a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template in molecular imprinting. The magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs) were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis and superconducting quantum interference device (SQUID) analysis. Natural killer-92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and the quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found significantly enhance the activity of natural killer cells toward HepG2 cells by increasing expression of NK-kB, caspase 8 and especially caspase 3.

A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia. Since the discovery of this translocation, many studies have focused on understating the role of the truncated isoform of DISC1, hypothesizing that the gain of function of this protein could be behind the neurobiology of mental conditions, but not so many studies have focused in the mechanisms impaired due to its loss of function. For that reason, we perform an analysis on the cellular proteome of primary neurons in which DISC1 was knocked down with the goal of identifying relevant pathways directly affected by DISC1 loss of function. Using an unbiased proteomic approach, we found that the expression of 31 proteins related to neurodevelopment (e.g. CRMP-2, stathmin) and synaptic function (e.g. MUNC-18, NCS-1) is regulated by DISC1 in primary mouse neurons. Hence, this study reinforces the idea that DISC1 is a unifying regulator of both neurodevelopment and synaptic function, thereby providing a link between these two key anatomical and cellular circuitries.

The rapid urbanization that takes place in developing regions such as Sub-Saharan Africa is associated with a large range of environmental and social issues. In this context, remote sensing is essential to provide accurate and up-to-date spatial information to support risk assessment and decision making. However, mapping urban areas remains a challenge because of their heterogeneity, especially in developing regions where the highest rates of misclassification are observed. Nevertheless, urban areas located in arid climates --- which are among the most vulnerables to anthropogenic impacts, suffer from the spectral confusion occurring between built-up and bare soil areas when using optical imagery. Today, the increasing availability of satellite imagery from multiple sensors allow to tackle the aforementioned issues by combining optical data with Synthetic Aperture Radar (SAR). In this paper, we assess the complementarity of the Landsat 8 and Sentinel-1 sensors to map built-up areas in twelve Sub-Saharan African urban areas, using a pixel-level supervised classification based on the Random Forest classifier. We make use of textural information extracted from SAR backscattering data in order to reduce the speckle noise and to introduce contextual information at the pixel level. Results suggest that combining both optical and SAR features consistently improves classification performances, mainly by enhancing the differentiation between built-up and bare lands. However, the fusion was less beneficial in mountainous case studies, suggesting that including features derived from a Digital Elevation Model (DEM) could improve the reliability of the proposed approach. As suggested by previous studies, combining features computed from both VV and VH polarizations consistently led to better classification performances. On the contrary, introducing textures computed from different spatial scales did not improve the classification performances.

This study investigates the cytotoxicity profile of superparamagnetic Fe3O4-Ag decorated nanoparticles against human fibroblasts (HFF-1) and breast cancer cells (MCF-7). The nanoparticles underwent comprehensive characterization employing scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS), and magnetic assays including hysteresis curves and zero-field-cooled (ZFC) plots. Notably, the nanoparticles exhibited superparamagnetic behavior as evidenced by magnetic studies. Remarkably, cytotoxicity assays demonstrated that both HFF-1 and MCF-7 cells maintained nearly 100% viability upon nanoparticle exposure. These results underscore the outstanding biocompatibility of Fe3O4/Ag decorated nanoparticles, suggesting their potential utility in biomedical applications such as drug delivery and magnetic targeting without inducing significant cytotoxic effects. This investigation advances our understanding of the behavior of nanostructured materials in biological settings and highlights their promising prospects in biomedicine.

This paper provides a new discovery that adds to the contemporary theory of modelling of non-stationary queues, by capturing analytically the behavior of the root parameter, for the G1/M/1 PSFFA model of non-stationary Ek/M/1 queue. Additionally, it has been also revealed that the resulting root parameter reduces to the PSFFA model of non-stationary queue. Potential applications of PSFFA to Computer engineering are provided. Some challenging open problems are addressed combined with closing remarks and future research directions.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

This conceptual, interdisciplinary paper will start by introducing the commencement of a new era in which human society faces continuously accelerating technological revolutions, named for short ‘Padkos’. In this context, a conceptual model of sustainable development with a focus on knowledge sharing and management will be proposed. The construct of knowledge management will be unpacked into a three-layer model with a focus on the knowledge-human and data-machine spheres. Then, each sphere will be discussed with concentrating on the learning and decision- making processes, the digital supporting systems and the human actors’ aspects. Moreover, the recombination of new knowledge development and contemporary knowledge management into one amalgamated construct will be proposed. The holistic conceptual model of knowledge sharing for sustainable development is comprised by time, cybersecurity and two alternative humanistic paradigms (Homo Technologicus and Homo Sustainabiliticus). Two additional particular models are discussed in depth. First, a recently proposed model of quantum organizational decision-making is elaborated. Next, a boundary management and learning process is particularized. The paper ends with several implications for the future based on the deliberations in the paper and the models discussed.

It has recently been discovered that mere cell contact by human cytomegalovirus (CMV) particles leads to profound modulation of cellular gene expression. Reduced monocyte human leukocyte antigen (HLA-DR) expression is a novel biomarker of severity and outcome in many diseases. Modulation of CD14 protein by CMV was shown in vitro, but little is known about the phenomenon in vivo (during active cytomegalovirus disease). Therefore, we investigated monocyte CD14 and HLA-DR expression in CMV infected patients in relation to logarithmic phase of infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. After CD45/SSC gating monocyte CD14 and HLA-DR expression were determined by double-color flow-cytometry. Significant monocytosis and poor correlation between CMV replication and CD14+HLA-DR(-) cells prompted CD14 investigation. During logarithmic phase of CMV infection increased count and percentage of CD14low monocytes were observed which correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, most of CD14low monocytes are HLA-DR+. The increase of CD14low monocytes is also observed under the influence of high dose of glucocorticoids (20 mg of dexamethasone). The reduction in CD14 induced by CMV and dexamethasone indicates that the monocyte balance is disturbed between the classical and non-classical phenotype. A high percentage of CD14lowHLA-DR+ probably gives rise to adaptive and a decrease of innate immune response. In light of the logarithmic increase of viral load (with exponent between 3,23 and 5,77), high monocytosis above 1200 / µl is a hallmark of CMV replication.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

The study aimed to determine the relationship between glucose, C-peptide, BDNF, and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with T1DM. According to the z-score for neonatal weight, patients were divided into Healthy weight neonates (n=42) and Overweight neonates (n=24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, CRP, leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, FT3, FT4, and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Increased odds for Overweight neonates were BMI, BDNF, and TSH in the first trimester of pregnancy. Maternal leptin concentration decreased the odds of Overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus’s glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, its fat body mass is responsible for increased leptin concentrations.

Observing cultivated crops and other forms of land use is an important environmental and economic concern for agricultural land management and crop classification. Crop categorization offers significant crop management data, ensuring food security, and developing agricultural policies. Remote sensing data, especially publicly available Sentinel 1 and 2 data, has effectively been used in crop mapping and classification in cloudy places because of their high spatial and temporal resolution. This study aimed to improve crop type classification by combining Sentinel-1 (Synthetic Aperture Rader (SAR)) data and the Sentinel-2 Multispectral Instrument (MSI) data. In the study, Random Forest (RF) and Classification and Regression Trees (CART) classier were used to classify grain crops (Barley and Wheat). The classification results based on the combination of Sentinel-2 and Sentinel-1 data indicated an overall accuracy (OA) of 93 % and a kappa coefficient (K) of 0.896 for RF and (89.15%, 0.84) for the CART classifier. It is suggested to employ a mix of radar and optical data to attain the highest level of classification accuracy since doing so improves the likelihood that the details will be observed in comparison to the single-sensor classification technique and yields more accurate results.

Fungal spores are universal atmospheric components associated to allergic reactions. Alternaria (Ascomycota) is considered the most allergenic spore taxa. Alt a 1 is the major allergen of Alternaria and is present also in other Pleosporales. In this study, standard Hirst-based sampling and analyzing methods for measuring spore daily concentrations of Alternaria, Curvularia, Drechslera-Helminthosporium, Epicoccum, Leptosphaeria, Pithomyces, Pleospora and Stemphyllium (all included in the taxon Pleosporales) have been used besides two high-volume samplers, Burkard Cyclone (2017) and MCV CAV-A/mb (2019-2020), and ELISA Kits for measuring the allergen. The detection and quantification of Alt a 1 was only possible in the samples from the MCV sampler. Although Alt a 1 was better correlated with Alternaria spores than with Pleosporales spores, the three of them showed high correlations. It is shown, for the first time, a high and significant correlation of Alt a 1 with temperature, a negative one with relative humidity and no correlation with precipitation. The aerobiological monitoring of these three elements ensures the best information for understanding the affectation to allergy sufferers but, if not possible, as a minimum public health service aiming at the detection, treatment and prevention of allergy, the study of the airborne Alternaria spores should be ensured.

Background: PRAME, NY-ESO-1 and SSX2 are cancer testis antigens (CTAs), which in normal tissues are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterized cohort soft tissue sarcomas (STS). Methods: On protein level, we examined PRAME, NY-ESO-1 and SSX2 expression in tumour tissues of 249 STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including Tumour-infiltrating lymphocyte (TIL) counts, grading and long- term survival. Results: Expression of PRAME, NY-ESO-1 and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo subtypes. Expression of PRAME was associated with shorter patient survival (p=0.005) and higher grade (G2 vs G3, p=0.001) while NY-ESO-1 expression was correlated with more favourable survival (p=0.037) and low grade (G2 vs G3, p=0.029). Both PRAME and NY-ESO-1 expression was more frequent in STS with low TILs counts. Conclusions: CTAs PRAME, NY-ESO-1 and SSX2 show distinct expression patterns in different STS subtypes. These results may guide future immunotherapeutic approaches in STS.

The co-circulation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Because ducklings infected with DHAV-1 or DHAV-3 show similar clinical signs and gross lesions, it is important to discriminate these subtypes as early as possible for better clinical management. On the basis of multiple alignments of the 5′-noncoding region sequences of strains DHAV-1 and DHAV-3, universal and type-specific primers were designed and synthesized. Using the primers in a one-tube reverse transcription-PCR (RT-PCR) assay, reference strains of DHAV-1 and DHAV-3 (isolated over a span of 60 years and covering many different countries) were successfully amplified, indicating that the primer sequences were completely conserved. The amplicon sequences results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates correlated completely with their genotypes. Moreover, with this one-tube RT-PCR system, the amplicon sizes of liver samples of reference DHAV-1- or DHAV-3-infected birds matched perfectly with their respective genotypes, as determined by virus isolation and neutralization tests. No other RNA viruses of duck origin were detected with the synthesized primers. The sensitivity of viral RNA detection was 10 pg. With this system, 20% genotype 1, 45% genotype 3, and 9% co-infection of the two genotypes were detected in 55 clinical samples. This novel approach could be used for the rapid genotyping DHAV-1 and/or DHAV-3 infection in routine clinical surveillance or epidemiologic screening.

Outlined is a proposal designed to culminate in the foundry fabrication of arrays of singly addressable quantum dot sources deterministically emitting single pairs of energy-time entangled photons at C-band wavelengths; each pair having negligible spin-orbit fine structure splitting; each pair being channeled into single mode pig-tail optical fibers. Entangled photons carry quantum state information among distributed quantum servers via I/O ports having two functions; the unconditionally secure distribution of decryption keys to decrypt publicly distributed, encrypted classical bit streams as input to generate corresponding qubit excitations, and to convert a stream of quantum nondemolition measurements of qubit states into a classical bit stream. Outlined are key steps necessary to fabricate arrays of on-demand quantum dot sources of entangled photon pairs, principal among are 1) foundry fabrication of arrays of isolated quantum dots, 2) generation of localized sub-surface shear strain in a semiconductor stack, 3) a cryogenic anvil cell, 4) channeling entangled photons into single mode optical fibers, 5) unconditionally secure decryption key distribution over the fiber network, 6) resonant excitation of a Josephson tunnel junction qubits from classical bits, and 7) conversion of a quantum nondemolition measurements of a qubit states into a classical bit.