Prostanoids modulate the pathogenesis of vascular diseases such as atherosclerosis, in which inflammation has an important role. It is well known that inducible Ciclooxygenase-2 (COX-2) is responsible for prostanoid production associated with inflammation. Angiotensin II may be implicated through the expression of COX-2 in the vascular wall. The purpose of this study was to examine in angiotensin II-stimulated adventitial fibroblasts the anti-inflammatory activity of different food peptides by inhibiting COX-2 expression, and the production of pro-inflammatory prostanoids. Fibroblasts from aorta of Sprague-Dawley rats were incubated with different food derived peptides followed by incubation with Angiotensin II. COX-2 expression was determined by western blot, transcriptional activity by luciferase assays and prostaglandin E2 by enzyme immunoassay. COX-2 expression was inhibited in the presence of Val-Pro-Pro (bovine β-casein 84–86), Arg-Asp-Ile-Leu-Asn-Gln (ovalbumin 84–89) and Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe (ovalbumin 125–134). Angiotensin II-induced prostaglandin E2 production was also reduced by all the above-mentioned sequences. The incubation with ovalbumin-derived peptides displayed a significant reduction of COX-2 promoter activity compared to the stimuli with Angiotensin II in transiently transfected cells. These three sequences could potentially be used as functional food ingredients to reduce inflammation related to cardiovascular diseases.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by re-stricted and repetitive behaviors as well as difficulties with social interaction. Nu-merous studies have revealed aberrant lipid mediators and autoimmunity as a recog-nized etiological cause of ASD that is amenable to therapeutic intervention. Methods: In this study, the relationship between the relative cyclooxygenase-2, / pros-taglandin E2 ratio (COX-2/PGE2) as lipid mediator marker and anti-nucleosome au-toantibodies as autoimmunity marker of ASD was investigated using multiple regres-sion and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty age- and sex-matched controls included in the current study. Results: Using combined ROC curve analysis, a notable increase in the area under the curve was seen. Additionally, it was reported that the combined markers had improved specificity and sensitivity. Conclusions: This study shows that using a ROC curve analysis to measure the predictive value of specific biomarkers linked to lipid metabolism and autoimmunity in children with ASD should improve our understanding of the etiological mechanism of ASD and how it is related to metabolism. Early diagnosis and intervention may be facilitated by this knowledge.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Fused deposition modeling (FDM) is widely applied in various fields due to its affordability and ease of use. However, it faces challenges such as achieving high surface quality, precise dimensional tolerance and overcoming anisotropic mechanical properties. This paper analyzes and compare the machinability of 3D printed PLA, PETG and carbon fiber reinforced PETG focusing on surface roughness and burr formation. A design of experiments (DoE) with a full factorial design was used, considering three factors: rotation speed, feed rate and depth of cut. Each factor had different levels: rotational speed at 3000, 5500 and 8000 rpm; feed rate at 400, 600 and 800 mm/min; and depth of cut at 0.2, 0.4, 0.6, and 0.8 mm. Machinability was evaluated by roughness and burr height using a profilometer for all the materials under the same milling conditions. To evaluate the statistical significance of the influence of various processing parameters on surface roughness and burr formation in 3D printed components made of three different materials PLA, PETG and carbon fiber reinforced PETG, an analysis of variance (ANOVA) test was conducted. This analysis investigated whether variations in rotational speed, feed rate and depth of cut resulted in measurable and significant differences in machinability results. Results showed that milling parameters significantly affect roughness and burr formation, with optimal conditions for minimizing any misalignment highlighting the trade-offs in parameter selection. These results provide insights into the post-processing of FDM-printed materials with milling, indicating the need for a balanced approach to parameter selection based on application-specific requirements.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Urbanization is considered as a main indicator of regional economic development due to its positive effect on promoting industrial development; however, many regions, especially developing countries, are troubled by its negative effect — the aggravating environmental pollution. Many researchers have indicated that rapid urbanization stimulated the expansion of industrial production scale and increased industrial pollutant emissions. However, this judgement contains a grave deficiency in that urbanization not only expands industrial production scales but can also increase industrial labour productivity and change the industrial structure. To modify this deficiency, we first decompose the influence which urbanization impacts on industrial pollutant emissions into the scale effect, the intensive effect and the structure effect by using the Kaya Identity and the LMDI Method; second, we perform an empirical study of the three effects’ impacts by applying the spatial panel model with data from 282 Chinese cities between 2003 and 2013. Our results indicate that (1) there are significant reverse U-shapes between Chinese urbanization rate and its industrial pollutant emissions; (2) the scale effect and the structure effect have aggravated Chinese industrial waste water discharge, sulphur dioxide emissions and soot (dust) emissions, while the intensive effect has generated a decreasing and ameliorative impact on that aggravated trend. The definite relationship between urbanization and industrial pollutant emissions depends on the combined influence of the scale effect, the intensive effect and the structure effect; (3) there are significant spatial autocorrelations of industrial pollutant emissions between Chinese cities, but the spatial spillover effect from other cities does not aggravate local urban industrial pollutant emissions, we offer an explanation to this contradiction that the vast rural areas surrounding Chinese cities have served as sponge belts and have absorbed the spatial spillover of cities’ industrial pollutant emissions. According to the results, we argue that this type of decomposition of the influence into three effects is necessary and meaningful, it establishes a solid foundation for understanding the relationship between urbanization and industrial pollutant emissions, and effectively helps to meet relative policy making.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

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.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/ prostaglandin E2 (PGE2) up-regulated by SiNPs toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNPs-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3‑kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

The Mobius function is commonly used to define Euler's totient function and the Mangoldt function. Similarly, the summatory Mobius function (the Mertens function) can be used to define the summatory totient function and the summatory Mangoldt function (the second Chebyshev function).

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately leads to recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from continued presence of the initial trigger, or dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults including centenarians is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death [1–3]. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing - it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity and mortality risk. While inflammageing was initially thought to be caused by “continuous antigenic load and stress”, reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and ageing of the immune system. In this review, we explore the sources and consequences of inflammageing and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise and pharmacological interventions can reduce inflammageing and thus improve later life health.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

Despite energy-related financial concerns and the growing demand for sustainability, many energy efficiency measures are not being implemented in industrial practice. There are a number of reasons for this, including a lack of knowledge about energy efficiency potentials and the assessment of energy savings as well as the high workloads of employees. This article describes the systematic development of an expert system, which offers a chance to overcome these obstacles and contribute significantly to increasing the energy efficiency of production machines. The system employs data-driven regression models to identify inefficient parameter settings, calculate achievable energy savings, and prioritize actions based on a fuzzy rule base. Proposed measures are first applied to an analytical real-time simulation model of a production machine to verify that constraints required for the specified product quality are met. This provides the machine operator with the expert means to apply proposed energy efficiency measures to the physical entity. We demonstrate the development and application of the system for a throughput parts cleaning machine in the metalworking industry.

The conventional rolled-up model for carbon nanocones assumes that the cone is constructed from a rolled-up graphene sheet joined seamlessly, which predicts five distinct vertex angles. This model completely ignores any effects due to the changing curvature and all bond lengths and bond angles are assumed to be those for the planar graphene sheet. Clearly curvature effects will become more important closest to the cone vertex, and especially so for the cones with the smaller apex angles. Here we construct carbon nanocones which in the assembled cone are assumed to comprise bond lengths and bond angles which are, as far as possible, equal throughout the structure at the same distance from the conical apex. Predicted bond angles and bond lengths are shown to agree well with those obtained by relaxing the conventional rolled-up model using the LAMMPS software. The major objective here is not simply to model physically realisable carbon nanocones for which numerical procedures are far superior, but rather to produce an improved model that takes into account curvature effects close to the vertex, and from which we may determine an analytical formula which represents an improvement on that for the conventional rolled-up model.

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

Porcine parvovirus 8 (PPV8), a novel virus in the Parvoviridae family, was first identified in 2022 in lung samples of domestic pigs from China. Retrospective analyses showed that it had been circulating in China since 1998, but no other countries had reported its presence so far. A recent study conducted in South America did not detect any PPV8-positive samples in that region. Here we report the detection of PPV8 in Hungarian and Slovakian pig farms and the estimated prevalence of the virus in Hungary. Altogether 2230 serum, 233 oral fluid, and 115 processing fluid samples were systematically collected from 23 Hungarian and 2 Slovakian pig farms between 2020 and 2023. A real-time quantitative PCR method was developed to detect the viral genome. Our results revealed the presence of PPV8 on 65% of the Hungarian farms and on both Slovakian farms included in our study, marking its first detection in Europe. Oral fluid samples showed the highest positivity rates, reaching up to 100% in some herds. The viral genome was successfully detected in serum and processing fluid samples too, but with significantly lower prevalence rates of 4% and 5%, respectively. Genetic analysis of 11 partial VP2 sequences demonstrated high similarity to the original Chinese strain but with unique amino acid mutations, suggesting possible local evolution of the virus. Our study presents the first scientific evidence of PPV8 infection outside of China and offers a comprehensive assessment of its prevalence in the Hungarian pig population. Further research is required to understand its potential impact on swine health.

This paper builds on previous work introducing the Secure Remote Update Protocol (SRUP)—a secure communications protocol for Command & Control applications in the Internet of Things, built on top of MQTT. This paper builds on the original protocol, and introduces a number of additional message types: adding additional capabilities to the protocol. We also discuss the difficulty of proving that a physical device has an identity corresponding with a logical device on the network, and propose a mechanism to overcome this within the protocol.

Chromium (Cr) metal has garnered significant attention in alloy systems owing to its exceptional properties, such as high melting point, low density, and superior oxidation and corrosion resistance. However, its processing capabilities are hindered by the high Ductile-Brittle Transition Temperature (DBTT). Recently, powder bed fusion-laser beam for metals (PBF-LB/M) has emerged as a promising technique, offering the fabrication of net shapes and precise control over crystallographic texture. Nevertheless, research investigating the mechanism underlying crystallographic texture development in pure Cr via PBF-LB/M still needs to be conducted. This study explores the impact of scan speed on relative density and crystallographic texture. At the optimal scan speed, an increase in grain size attributed to epitaxial growth was observed, resulting in the formation of cubic texture. Consequently, a reduction in High Angle Grain Boundaries (HAGB) was achieved, suppressing defects such as cracks and enhancing relative density up to 98.1%. Furthermore, with increasing densification, Vickers hardness also exhibited a corresponding increase. These findings underscore the efficacy of PBF-LB/M for processing metals with high DBTT properties.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

The Fuzzy Transportation Problem (FTP) represents a significant extension of the Classical Transportation Problem (TP) by introducing uncertainly and imprecision into the parameters involved. Various algorithms have been proposed to solve the FTP, including fuzzy linear programming, metaheuristic algorithms and fuzzy mathematical programming techniques combined with Artificial Neural Networks. This paper presents the application of Trigonometric Acceleration Coefficients-PSO (TrigAc-PSO), a variation of the Classical Particle Swarm optimization algorithm, which is an innovative algorithm originally developed for solving the TP. TrigAC-PSO, has demonstrated remarkable success in optimizing various problem domains in crisp environments.

The apicomplexan parasite, Sarcocystis neurona causes the degenerative neurological equine protozoal myeloencephalitis (EPM) disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions such as host cell invasion, cell cycle progression and host immune responses evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. Further, three-dimensional (3D) homology models for selected S. neurona putative PKs were constructed and evaluated for inhibitor docking. We identified 92 putative PKs clustering within the AGC, CAMK, CK1, CMGC, STE, TKL, aPK and OPK groups. Although containing the universally conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC, but contained the six apicomplexan conserved CDPKs (CAMK group). The OPK group was represented by ROPKs 19A, 27, 30, 33, 35 and 37, but was devoid of the virulence-associated ROPKs 5, 6, 18 and 38. Two out of the three S. neurona CK1 enzymes had high sequence similarities to T. gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Docking of four inhibitors onto homology models of putative ROP27 and PKA indicated that inhibition of S. neurona PKs is feasible, but needs to be experimentally tested. The essentiality of apicomplexan PKs makes the elucidation of S. neurona kinome a key milestone for development of novel therapeutics for EPM.

Cybersecurity is a crucial concern for local governments, as they serve as the primary interface between public and government services, managing sensitive data and critical infrastructure. While technical safeguards are integral to cybersecurity, the role of well-structured policy is equally important, as it provides structured guidance to translate technical requirements into actionable protocols. This study reviews local governments’ cybersecurity policies to provide a comprehensive assessment of how these policies align with NIST CSF, which is a widely adopted and commonly used cybersecurity assessment framework. The review offers local governments a mirror to reflect on their cybersecurity stance, identifying potential vulnerabilities and areas needing urgent attention. The study further extends to developing a cybersecurity policy framework, which local governments can use as a strategic tool. It provides valuable information on crucial cybersecurity elements that local governments must incorporate into their policies to protect confidential data and critical infrastructure.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS > 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (< 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS > 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

The paper provides and comments on the results of studies of the effect of sandstone-based abrasives and quartz sand alone on the wear of martensitic surfaces of wear-resistant steels. The wear process was examined on a ring-on-ring test rig seeking to determine the mass decrement parameter which characterised wear. The tests were conducted for three sandstone varieties: Carboniferous, Permian, and Cretaceous, and they made it possible to determine that the most intense process of deterioration of wear-resistant steels took place in the presence of quartz sand grain, while less intense wear was observed in the case of sandstone-based abrasives. The mass decrement values established in the presence of the sandstones in question did not differ significantly between individual sandstone varieties. Based on a surface damage analysis, the basic damage mechanism was found to be micro-scratching, however, with regard to the sandstones examined, it was also determined that individual grains could be pressed into surface irregularities, as well as that films of soft hematite cement developed in the Permian sandstone and that inclusions of carbonaceous matter were formed in the Carboniferous sandstone. With reference to the wear process observations, a wear model was described for the surface of the steels examined in the presence of sandstone-based abrasives.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

A generalization of the sum of divisors function involves a recursive definition. This leads to variants of superabundant numbers, colossally abundant numbers, and Gronwall's theorem (relevant to the Riemann hypothesis).

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but those most noteworthy include treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and the individual bee. The use of medical grade honey, Medihoney and Revamil, in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, medical grade honeys should be used for these treatments and reduce the demand for antibiotic usage. In this review, we aim to outline the constituents of honey and how they affect the antibiotic potential of honeys in a clinical setting.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

In an era marked by swift technological progress, the pivotal role of Artificial Intelligence (AI) is increasingly evident across various sectors, including local governments. These governmental bodies are progressively leveraging AI technologies to enhance service delivery to their communities, ranging from simple task automation to more complicated engineering endeavours. While more and more local governments are adopting AI, it is imperative to understand the functions, implications, and consequences of AI. Despite the growing importance of this domain, a significant gap persists within the scholarly discourse. This study strives to bridge this void by exploring the applications of AI technologies within the context of local government service provision and using this inquiry to generate lessons and best practices for similar smart city initiatives. Through a comprehensive grey literature review, we analysed 262 real-world AI implementations across 170 local governments worldwide. The findings underscore several key points: (a) There has been a consistent upward trajectory in the adoption of AI by local governments over the last decade; (b) Local governments from China, the US, and the UK are at the forefront of AI adoption; (c) Among local government AI technologies, Natural Language Processing and Robotic Process Automation emerge as the most prevalent ones; (d) Local governments primarily deploy AI across 28 distinct services; (e) Information management, back-office work, and transportation and traffic management are leading domains in terms of AI adoption. This study enriches the extant body of knowledge by providing an overview of existing AI applications within the sphere of local governance. It offers insights for smart city policymakers and decision-makers considering the adoption, expansion, or refinement of AI technologies in urban service provision. Additionally, it underscores the importance of using these insights to guide the successful integration and optimisation of AI in future smart city projects, ensuring they meet the evolving needs of communities.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included into animal feed mixtures due to the presence of Kunitz (KTi) and Bowman Birk protease inhibitors (BBi) which reduces animal performance. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBi) but such treatment is energy intensive, adds expense, and negatively impact the quality of seed proteins. As an alternative approach we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays and q15RT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss of function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Purpose: Pandemic Novel Coronavirus (SARS-CoV-2) has emerger centered from wuhan, China. Structurally homologous spike protein of SARS-CoV-2 receptor is taxonomically homologous with SARS-Cov and SARS associated bat coronavirus. Still now scientists are trying to find out proper vaccine and treatments for this disease. Methods: Systematically we modeled and compared the structure of SARS-CoV-2 spike protein along with Bat Cov, Bat SARS Cov and SARS Cov Urbani. S1 and S2 unit of the coronavirus (SARS-CoV-2) are attached with ACE2 and furin, here we docked 5 Ca+ chelating drugs with these two proteins. Results: Structural comparison with all these spike proteins revealed that less significant but not negligible difference exists among them. Inserted stable nucleotide sequences and corresponding surface exposed peptidal region may be considered as epitope. Docking result with Toxicokinetics and half life of Penicillamine can effectly inhibit the attachment site of spike protein of coronavirus (SARS-CoV-2). Conclusions: Docking summery and the pharmacokinetics with toxicokinetics index recommend that Penicillamine can able to inhibit the infection of SARS-CoV-2.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

This paper examines dynamic identity, as it pertains to the IoT; and explores the practical implementation of a mitigation to some of the key weaknesses of a conventional dynamic identity model. This paper explores human-centric and machine-based observer approaches for confirming device identity, permitting automated identity confirmation for deployed systems. It also assesses the advantages of dynamic identity in the context of identity revocation permitting secure change of ownership for IoT devices. The paper explores use-cases for human and machine-based observation for authentication of device identity when devices join a C2 network, and considers the relative merits for these two approaches for different types of system.

Purpose: A number of imaging readout schemes have been proposed for renal arterial spin labelling (ASL) to quantify kidney cortex perfusion, including gradient echo based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo based schemes of spin-echo echo planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Methods: Ten healthy volunteers with normal renal function were scanned using each 2D multislice imaging scheme, in combination with a respiratory triggered FAIR (flow-sensitive alternating inversion recovery) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. Results: For each imaging scheme, renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100 g/min, GE-EPI: 222 ± 18 mL/100 g/min, SE-EPI: 201 ± 36 mL/100 g/min, TSE: 200 ± 20 mL/100 g/min). Perfusion was found to be higher for GE based readouts compared to SE based readouts, with significantly higher measured perfusion for the bFFE readout compared to all other schemes (P < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI compared to all other schemes (P < 0.05), the SE-EPI readout gave the highest tSNR and was found to be the most reproducible scheme for the assessment of kidney cortex, with a CoV of 17.2%, whilst minimizing variability of the perfusion weighted signal across slices for whole kidney perfusion assessment. Conclusion: For the assessment of kidney cortex perfusion, SE-EPI provides optimal tSNR, minimal variability across slices and repeatable data acquired in a short scan time with low specific absorption rate.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

A novel interaction between the enzyme platelet-activating factor acetyl hydrolase (PAF-AH) and certain non-steroidal anti-inflammatory drugs (NSAIDs), such as sulindac, celecoxib, diclofenac and nimesulide, has been uncovered by this in-silico research. PAF-AH is known for its critical role in maintaining the fluidity and functionality of cell membranes by hydrolysing phospholipids and removing oxidized fatty acids. Since tumour microenvironments are largely marked by inflammation and oxidative stress, the discovery that these non-steroidal anti-inflammatory drugs can bind to the active pocket of PAF-AH. Suggests that they may be able to modulate its activity and thereby influence its role in cancer pathogenesis. Such modulation could lead to significant anti-tumour effects, including the reduction of inflammation, the inhibition of angiogenesis and the suppression of metastasis, particularly in cancers of the breast, colon, prostate, and lung. However, in certain con-texts, this interaction may cause the opposite effect, leading to cancer development. Therefore, this study is a gateway for the development of therapeutic strategies based on PAF-AH modulation and highlights the importance of the tumour microenvironment in the assessment of potential effects of NSAIDs. Furthermore, this finding may guide the selection of NSAIDs for the anti-inflammatory treatment of cancer patients, ruling out in-discriminate use of drugs that may promote neoplastic progression. This may also indicate the potential for repositioning specific NSAIDs within cancer treatment, thereby contributing to more precise and personalized therapeutic approaches.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

The mechanical properties of the materials stored inside agricultural silos influence the loads generated inside them. The different silo calculation methodologies allow predicting these loads under static and dynamic conditions if the mechanical properties of the stored materials are known. It has been known for many years that these properties are highly dependent on the moisture content of the material. However, to date there are not many studies focused on its determination. The goal of this research is the determination of the angle of internal friction, apparent cohesion, dilatancy angle and apparent specific weight of maize subjected to different moisture contents. Direct shear and oedometer assay devices were used for this purpose. In addition, the maize samples used were moistened using a climatic chamber. Moisture contents applied to maize sample ranged from 9.3% to 17.4%. The results obtained for the angle of internal friction and apparent cohesion, as well as those obtained for the apparent specific weight, were similar to those reported in the literature. However, the values obtained for the dilatancy angle of maize as a function of moisture content could not be compared because nothing has been published so far. The values obtained for this parameter overlap with those published for this material under ambient conditions. In addition, no direct relationship between the values obtained for this parameter and the moisture content of the sample could be found. Finally, the apparent specific weight increased with increasing moisture content of the samples, which differed from that published in the literature. The values provided here can be used for the optimization of storage and handling structures for granular agricultural materials using numerical methods.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

Background: Removable prostheses have seen a fundamental change recently because of advances in polymer materials, allowing improved durability and performance. Despite these advancements, notable differences still occur amongst various polymer materials and processing technologies, requiring a thorough grasp of their mechanical, physical, and therapeutic implications. Methods: Fours different processing techniques, all utilizing Polymethyl methacrylate (PMMA) as the main material, were used to construct complete dentures. The specimens underwent a mechanical test. Results: All the specimens broke under the influence of a certain force, rather than yielding through flow, as is characteristic for plastic materials. For each specimen, the maximum force (N) was recorded (figure 4), as well as the breaking energy, Conclusions: The best results were obtained in the case of the thermoplastic injection system and, surprisingly and contrary to those in the specialized literature, the worst results were recorded in the case of 3D printed samples.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

In the Vietnamese Mekong delta, soil quality and crop yield are steadily declining under rice monocultures with three crops per year. The objective of this study was to evaluate the medium-term effects of rotating rice with upland crops and adding organic amendments on rice yield and relate it to soil quality. A field trial with split-plot design including two factors and three replicates was carried out from 2017 to 2020, over the course of nine consecutive cropping seasons. Crop rotations and organic amendments were applied as main-plot and subplot factors, respectively. The rotations were: 1) rice–rice–rice (R–R–R), 2) soybean–rice–rice (So–R–R), and 3) sesame–rice–rice (Se–R–R), while organic amendment treatments included: i) no amendment (NO-AM); ii) compost of rice straw and cow manure (RS+CM), and iii) sugarcane compost (SGC); the composts were applied at a rate of 2.0 t ha-1. The rotation cycle started with the so-called spring–summer (SS), followed by summer–autumn (SA) and ended with the winter–spring (WS) season. Rice yield significantly (P &lt; 0.05) increased by organic amendments after nine growing seasons (2019–2020 WS), with an increment of 5.1% for RS+CM (7.07 ton/ha) and 6.1% for SGC (7.14 ton/ha). Contrary to our expectation, rotations with upland crops did not significantly increase rice yield. Rice yield significantly and positively correlated with an integrated soil quality index SQI (r = 0.86) for the topsoil (0–15 cm), but not for the subsoil (15–30 cm). The increased availability of soil nutrients (Si and marginally also P) and improved soil physical properties probably induced by organic amendments, along with other soil properties under study, cumulatively attributed to enhanced rice yield. Use of a SQI involving several soil quality indicators enables to overall quantify the importance of soil fertility for rice yield versus other factors and it provides an effective means of quantifying the integrated effect of improved management. Moreover, integrating a wide range of soil quality indicators in a SQI ensures its applicability across diverse settings, including different crop rotations and various soil types.

: This study focuses on optimizing chlorophyll extraction techniques and strategically placing leaf disks to enhance chlorophyll concentration in sesame (Sesamum indicum L.) leaves. Thirty sesame genotypes, categorized into light green (LG), middle green (MG), and deep green (DG) pigment groups based on leaf coloration, were selected from a larger pool of field-grown accessions. The investigation involved determining optimal SPAD value index measurements, quantifying pigment concentrations, exploring extraction solvents, and selecting suitable leaf disk positions. Significant variations in chlorophyll content were observed across genotypes, greenness categories, and leaf disk positions. The categorization of genotypes into DG, MG, and LG groups revealed a correlation between leaf appearance and chlorophyll content. The study highlighted a consistent relationship between carotenoids and chlorophyll, indicating their role in adaptation to warm environments. Examination of leaf disk positions revealed a significant chlorophyll gradient along the leaf blade, emphasizing the need for standardized protocols. Chlorophyll extraction experiments identified DMSO and 96% ethanol, particularly the later incubated for 10 minutes at 85°C, as effective choices. This recommendation considers factors like cost-effectiveness, time efficiency, safety, and environmental regulations, ensuring consistent and simplified extraction processes. For higher chlorophyll extraction, focusing on leaf tips and the 75% position along the sesame leaf blade is suggested, consistently yielding higher chlorophyll content. Our findings therefore, underscores insightful knowledge on chlorophyll gradients and encouraging for standardized protocols, that enabling researchers to refine experimental designs for precise and comparable chlorophyll measurements. Recommended solvent choices ensure reliable outcomes in plant physiology, ecology, and environmental studies.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

Brand trust holds significant importance in the Mongolian cashmere industry. This study examines the primary predictors of customer brand trust among Mongolian cashmere users. Our research includes a survey with 800 participants and 20 individual interviews conducted among both Mongolian cashmere users and non-users. We utilized an online platform to reach participants, employing convenience sampling. The study investigates the relationship between various factors and brand trust within the context of Mongolian cashmere brands. Through a combination of in-dividual interviews and statistical analysis, we test six hypotheses. The findings indicate that higher brand quality, a strong reputation, greater transparency, effective issue resolution, commitment to environmental and social responsibility, and pre-purchase research on such commitments positively impact brand trust. Key insights gleaned from the interviews emphasize the importance of quality, reputation, transparency, customer service, and environmental responsibility in shaping consumer trust. These results offer valuable implications for cashmere brands aiming to bolster consumer trust and foster loyalty.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O2), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, Oxygen nanoBubbles (OnB), an emerging versatile oxygen de-livery platform, implies to offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

The growing expansion of the economy and population has resulted in an increased inclination towards the utilization of groundwater resources. Conducting a geophysical survey is a widely employed method for subsurface mapping and the detection of groundwater. A geophysical study was conducted in Nanshan township, Huarong County, located in the Hunan province of the South-Central region of China. The investigation involved the utilization of a 2D Electrical Resistivity Imaging technique employing forward and inverse pole-dipole electrode array. A total of six survey lines were established, each with an electrode distance from the nearest measuring point to exceeding 800 m. The maximum current electrode separation was utilized in this setup. The spacing between the electrical resistivity sounding points was established at regular intervals. The findings from the exploration indicate the existence of multiple faults within the surveyed region. The study additionally identified two regions of structural failure, which occurred due to the convergence of faults oriented in different directions. This convergence led to the fracturing of rocks, an increase in water content, and a decrease in resistivity. The findings from the exploration were utilized in the formulation of five verification target boreholes. The results of this study offer significant insights that can inform future investigations into groundwater exploration endeavors within the region.

New furan, thiophene and triazole oximes were synthesized through several-step reaction paths to investigate their potential for development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Acute OP poisoning is still a challenge in treating patients despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, are blocked by the OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to cholinergic crisis. Oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper we described the synthesis of 63 heterostilbene derivatives out of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents – sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in micromolar range, we identified several oximes as BChE or AChE selective inhibitors with a potential for drug development. Moreover, even oximes were poor reactivators of AChE, four heterocyclic derivatives reactivated the cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had comparable reactivation efficacy to the standard oxime HI-6. In silico analysis and molecular docking studies connected the kinetic data to the structural features of these oximes, and confirmed their productive interactions with the active site of the cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting FAK and the TGF-β pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, β-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

The paper provides a discussion on the results of studies of the effect exerted by combined degradation factors typical of four types of wear: abrasion, impact-abrasion, tribocorrosion, and impact-abrasion-corrosion, conducted for chain wheels made of Ni-Cu alloyed Austempered Ductile Iron. The studies consisted in determining the content of retained austenite in the structure of the cast irons in question, establishing the measures of wear following wear testing, and identifying basic surface degradation mechanisms observed in the chain wheels tested following multifactorial wear processes. The chain wheels made of ADI were found to have sustained the greatest damage under the impact-abrasion-corrosion (three-factor) wear scenario, while the wear was least advanced in the abrasion (one-factor) wear case. Another observation derived from the studies is that the combined effect of dynamic forces, corrosion, and quartz sand-based abrasives causes increased surface degradation in the cast iron grades taken into consideration compared to processes characterised by a reduced number of degradation factors (i.e. one- or two-factor wear processes). Additional hardness tests and XRD analyses have revealed a distinctive effect attributable to combined degradation factors on the surface hardness increase value and implied that bench testing was followed by phase transition.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on 1st instar mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti Another goal was to identify which components of the extracts were responsible for any observed larvicidal activity. We found that methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC50: 4.4 ppm) and PR (LC50: 4.3 ppm) strains within 48 hours. Partitioning of the dried leaf extract between methanol and revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.

Objective: The effect of long-term performance of one-bottle or two-bottle bonding agents on the shear bond strength to lithium disilicate ceramics (LDS) were to investigate, and the long-term performance of the bond strength of two-bottle bonding agent (Tokuyama Universal Bond II) was investigated under conditions without hydrofluoric acid solution (abbreviated as HF)-pretreatment of LDS. Methods: Nine resin cements (both self-adhesive and adhesive types) were used. It was investigated 1) the adhesion strength of various resin cements to LDS from the presence or absence of HF-treatment, 2) to determine the effect of the deterioration in three times [after one-day storage (abbreviated as Base), and after 5,000 &amp; 20,000 thermocycles (abbreviated as TC 5k and TC 20k)] of one- and two-component bonding agents. And the difference in degradation between one- and two-component bonding gents consist of the silane coupling agent was performed by chemical analysis (High Performance Liquid Chromatography). Results: The trends of resin cements were statistically not very different for each cement 3 times with HF-conditions. Also ESTECEM II and Super-Bond Universal showed the significant greatest values in two conditions (TC 5k and TC 20k) without HF-condition. In TC 20k, ESTECEM II &amp; Super-Bond Universal showed significantly better results than others when treated with the recommended bonding agents without HF-condition. In TC 20k, there was not much statistically significant difference if pretreated with Tokuyama Universal Bond II without HF-condition. Significance: When using LDS, it was found that long-term durability could be maintained by pretreating with Tokuyama Universal Bond II without pretreating with various hazardous HFs.

Long COVID-19 affects a significant percentage of survivors and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to the immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system, altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long-term COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes—interventions that target the microbiome—may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. It is clear that more research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.

Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere-based scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure. Utilizing the extrusion printing process, we established a methodology which not only allows to create large microsphere-based scaffolds but also multicomposite matrices into which cells, growth factors, and therapeutics encapsulated in microspheres can be directly deposited during the printing process. Our 3D-McMap method addresses issues with scaffold shape fidelity during and after printing. Carefully timed breaks, minuscule drying steps, and adjustments to extrusion parameters, generated an evenly layered large microsphere-based scaffold that retains its internal architecture. Such scaffolds are superior to other microsphere-containing scaffolds, as they can release biomolecules in a highly controlled spatiotemporal manner. This capability permits to study cell responses to the delivered signals, to develop scaffolds that precisely modulate new tissue formation.

The ongoing challenge to ensure a sustainable and affordable energy supply forces industrial companies to implement appropriate measures. These measures typically lead to an increased system complexity, which has to be addressed during operation. Whereas existing approaches from the field of supervisory and optimal control appear to be capable of mastering this issue, these are still not adopted in industry. Therefore, this work presents a procedure model for the systematic development of application-oriented operating strategies for industrial energy supply systems. The procedure model combines research approaches from the fields of sequencing control and approximate MPC to extract rule-based operating strategies. By splitting the procedure model into five phases, expert knowledge can be integrated in a target-oriented manner. Subsequently to the description, the procedure model is exemplary applied to the example of an industrial heating supply system. Throughout an optimization study, the developed operating strategy is compared to a MPC strategy as well as a baseline strategy. Whereas the conventional MPC approach is the upper bound with regard to optimality, the developed operating strategy is able to generate comparable results. Compared to the baseline strategy, a relative reduction in operating expenses of 5.4 % to 37.0 % are achieved in this specific use case.

Green synthesis of silver nanoparticles (AgNPs) using raw Whey has never been reported. Silver nanoparticle formation involves a reduction reaction of silver salt solution with Whey extract. Extract and metal salt concentrations, and temperature can control this reaction. In this work, incubation period, extract, AgNO3, and NaOH concentrations were used as the independent factors using central composite design under response surface methodology. The aim was to elucidate the influence these factors have on the measured UV-Vis absorption spectra fitted with a Voigt function, and to optimize the conditions for nanoparticle formation. The fitting parameters, peak wavelength (λ0), peak area (A), and Full Width at Half Maximum (FWHM), were the responses. Silver nanoparticle formation was only possible in an alkaline environment (pH 10). The peak wavelength and the FWHM are influenced mainly by extract and AgNO3 concentrations. In contrast, the peak area is influenced by a total of 33.54 % from the interaction terms of AgNO3 and extract concentrations with NaOH. Metallic AgNPs were formed for the following parameter ranges: a) Whey (0.4 – 1.6 % v/v), b) AgNO3 (0.15 – 0.6 mM), c) NaOH (10 – 50 mM), and d) Time (20 – 60 min). Silver oxide nanoparticles were also observed.

In this work SiC-Ti3AlC2 and TiC-Ti3AlC2 composites produced by additive manufacturing are investigated. The fused granules fabrication (FGF) method as one of the material extrusion additive manufacturing (MEAM) technology is used to obtain composite samples. Composites with different ratios between components and different powder:polymer ratios are investigated. The technological features of the additive formation of composites are investigated, as well as their structure and properties. The optimal sintering temperature to form the best mechanical properties for both composites is 1300 °C. The composites have a regulatable porosity. Ti3AlC2 content, sintering temperature, and polymer content in the feedstock are the main parameters that regulates the porosity of FGF samples.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, i.e. Mycobacterium tuberculous complex and Mycobacterium leprae, respectively. The latter group is undoubtedly the most infamous, with TB infecting an estimated 10 million people and causing over 1.2 million deaths in 2017 alone (1). TB and leprosy also differ from NTM in that they are only transmitted from person to person and have no environmental reservoir, whereas NTM infections are commonly acquired from the environment (2) (3). It took until the 1950's for NTM to be recognised as a potential lung pathogen in people with underlying pulmonary disease and another 3 decades for NTM to be widely recognised by the medical community when NTM, particularly Mycobacterium avium complex (MAC) was recognised as the most common group of opportunistic pathogens in AIDS patients (4). This review focusses on an emerging NTM called Mycobacterium abscessus (M. abs). M. abs is a rapidly growing (RGM) NTM that is responsible for opportunistic pulmonary infections in patients with structural lung disorders such as cystic fibrosis (CF) and bronchiectasis (5), as well as a wide range of skin and soft tissue infections (SSTIs) in humans (6) (7). M. abs is a weakly staining Gram-positive mycobacterium that is neverand is, like other NTM, most often seen in soil and aquatic environments (8). The bacillus-shaped bacterium is 1-6µm long and 0.2-0.5µm in diameter, with curved ends and the presence of cord factor, or trehalose 6-6'-dimycolate, a glycolipid found in the cell wall of virulent species of mycobacteria that results in "serpentine cord" cell morphology is sometimes observed (8) (9). On solid growth medium, M. abs can display either a rough (M. abs-R) or smooth (M. abs-S) morphotype, with the rough morphotype displaying a more virulent phenotype than its smooth variant (10). The rough morphotype is characterised by irregular parallel filaments that form ridges across the colony, whereas a smooth morphology is displays a wet, smooth colony with no filaments or ridges (79). This morphology is driven by cell wall glycopeptidolipid (GPL); a loss of GPL results in the reversion from rough to smooth morphotype (80) (81). Moreover, it has been shown using human tissue culture models of infection that M. abs-R is able to persist and multiply within the host macrophage whereas M. abs-S lacks this capacity, hence its role in virulence (82). Like all other mycobacteria, M. abs are aerobic, non-motile and acid-fast organisms with a characteristically thick, lipid-rich cell wall that is hydrophobic. Due to their unusually impermeable, thick cell wall, mycobacteria are notoriously resistant to many antibiotics, disinfectants and heavy metals (11). When the genome of M. abs became available in 2009, elucidation of the resistance mechanisms of M. abs became an area of focus for scientific research, as the considerable threat it poses to public health became more apparent (12) (13) (14). In this review we will discuss how we came to understand the pathogen, how it is currently treated, as well as a discussion of drug resistance mechanisms and novel treatments currently in development.

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and an UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogels pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC-spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies.

The aim of the study is to obtain a more complete picture of the blood plasma melatonin concentration in the donkey species. To this purpose sampling and statistical processing were carried out in such a way that allowed to establish the annual and daily rhythm. Based on human observations, according to the hypothesis of the authors, the blood plasma melatonin concentration of pregnant individuals rises during late gestational period, before parturition. To confirm this, the melatonin concentration of pregnant and non-pregnant mares was monitored and compared. In regard to the circannual rhythm, the significantly lowest midnight melatonin value (27.67 pg/ml) is typical for the summer solstice. Under consideration of circadian changes, a significantly strongest melatonin production (45.16 pg/ml) can be observed on the night of the winter solstice (p &lt; 0.001). Considering the gestational age, the blood plasma melatonin concentration (around 38 pg/ml) does not change as pregnancy progresses (p = 0.136). The results obtained in the study population of the domestic ass usefully expand the little knowledge previously gathered about the development of blood plasma melatonin concentration of this species.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

Accompanied by increasing population growth and urban sprawl, most coastal cities are unprecedentedly vulnerable to climate change and its impacts, such as sea level rise, increasing extreme storm events, and coastal flooding. Coastal resilience and sustainable development are antidotes to vulnerability; they aim to enhance the adaptive capability of absorbing disturbances and resisting uncertainty. This study explores building a quantitative assessment framework to measure resilience and provide an objective and comparable method to understand the strengths and weaknesses in a given region. The proposed 25 resilience indicators incorporate the aspects of essential livelihood protection, infrastructure and natural resource maintenance, emergency facilities and institutions, floodplain management regulations, and adaptive planning process. Each indicator is assigned the resilience quality that includes robustness, resourcefulness, redundancy, and rapidity. The aggregated resilience quality scoring reflects the systematic performance of the city to cope with the coastal hazards. The innovative part of this framework is combining hazard mitigation measures, climate adaptation strategies, and sustainable development goals together to achieve a comprehensive assessment method. In the case of New Haven, the resilience assessment is taken as a practical monitoring tool and decision-making support.

In the British setting, the deployment of the phrase ‘doing god’ has become increasingly common to refer to an emerging trend whereby religion has acquired an increasingly prominent role in political spaces and discourses. This was particularly prominent while David Cameron was Prime Minister and leader of the Conservative Party. While historically, religion has not had a prominent place in either the former Prime Minister David Cameron. Here, the findings from critical analyzing a series of Cameron’s public pronouncements about religion—and Christianity in particular—is set out to try and better understand his own adherence to Christianity (the personal) how this intersected with his politics and role as Prime Minister (the political), and more importantly how this shaped his views about Britain being a Christian country (the national). Contextualised within the embryonic scholarly literature relating to the phenomenon of ‘doing god’ in the contemporary British setting, this article concludes by considering alternative and analogous frames through which greater elucidation of the true motivations of his pronouncements might be understood.

Abstract: Toxicity of emerging organic pollutants to photosystems of aquatic plants are still not well clarified. This study aimed to develop a novel ecotoxicological experimental protocol based on nanoscale electrochemical mapping of photosynthetic oxygen evolution of aquatic plants by SECM (scanning electrochemical microscopy). The protocol was also checked by confocal laser scanning microscopy (CLSM), the traditional Clark oxygen electrode method and chlorophyll fluorescence technique. The typical persistent organic pollutant 2,4-dichlorophenol (2,4-DCP) in water environment and the common aquatic Microsorium pteropus (M. pteropus) were chosen as the model organic pollutant and tested plant, respectively. It was found that the SECM method could well discriminated the responses of stoma micromorphology and spatial pattens of photosynthetic oxygen evolution on single stoma. The shape of stoma blurred with increasing 2,4-DCP concentration, which was in good agreement with the CLSM images. The dose-response curves and IC50 values obtained from the SECM data were verified by the data measured by the traditional Clark oxygen electrode method and chlorophyll fluorescence test. The IC50 value of single stoma oxygen emission of 24 h exposed plant leave, which was derived from the SECM current data (32535 μg L-1), was close to those calculated from the maximum photosynthetic efficiency (Fv/Fm) measured by chlorophyll fluorescence test (33963 μg L-1), and the Clark oxygen electrode method photosynthetic oxygen evolution rate (32375 μg L-1). The 72 h and 96 h 2,4-DCP exposure data further confirmed the reliability of the nanoscale stoma oxygen emission mapping methodology for ecotoxicological assessment. In this protocol, the procedures for how to collect effective electrochemical data and how to extract useful information from the single stoma oxygen emission pattern were well established. This study showed that SECM is a feasible and reliable ecotoxicological tool for evaluation of toxicity of organic pollutants to higher plants with unique nanoscale visualization advantage over the conventional methods.

Cocoa bean shells (CBSs) represent the external layer of cocoa beans. The shells are removed during the winnowing after the pre-roasting, a processing step of chocolate production; in in the past they were considered a waste. CBSs possess many interesting nutritional characteristics in both macro and micronutrients. CBSs result very rich in dietary fiber and antioxidant compounds such as phenolic acids and flavan-3-ols. Soluble dietary fibers are potentially associated with fermentability and prebiotic activity on human gut microbiota instead antioxidants compounds have been linked with positive effects on human health. Based on these properties, the aim of this study was the valorization of CBSs thorough enzymatic treatments. The shells were treated both raw and defatted; three sets of carbohydrases have been used in order to destructure the fiber profile, potentially enhancing the potential prebiotic activity of CBSs. Cellulase, xylanase and pectinase were used to perform enzymatic treatments. After the enzymatic hydrolisis, both soluble and insoluble fibers fraction were quantified, in parallel with the total phenolic and the total flavonoid contents and the antioxidant activity. Moreover, the HPLC-PDA analysis was carried out for the main compounds of CBSs. The enzymatic treatmens allowed to obtain an enhancement in soluble fibers, for both defatted and raw CBSs, particularly using cellulase, xylanase and their combinations. Finally, a parallel preservation of the antioxidant capacity and the content of the main bioactive compounds after the treatments was observed. These results can be used to exploit the enzymatic treated CBSs to further industrial applications in the food and nutraceutical fields.

The creation of the National Muslims Women’s Advisory Group (NMWAG) in 2008 by Britain’s New Labour Government was part of a strategy which sought to engage different levels of Muslim communities beneath an overarching focus on reducing ‘Islamic extremism’. To do so however, Government acknowledged that it would need to support Muslim women to overcome some of the constraints it believed were placed on Muslim women in contemporary Britain. Deeming theology and religious interpretation to be one of those constraints, Government saw the need to empower Muslim women to ‘influence and challenge’ religious and theological discourses as a priority. This article therefore offers a case study on a project that was commissioned by Government that sought to empower Muslim women to ‘influence and challenge’ theological interpretations in collaboration with the NMWAG. Having gained unprecedented access to the NMWAG, its activities and engagement with Government, this article presents previously unpublished findings from that project to focus on two key themes: Muslim women, their identity and position; and theology, leadership and the participation of women. Having explored these in detail, this article concludes by critically reflecting on the way in which Government engaged and interacted with Muslim women, the role and relative success of the NMWAG and, most importantly, the extent to which the NMWAG was able to ‘influence and challenge’ interpretations of Islamic theology.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Estrogen decline during menopause is associated with altered metabolism, weight gain and increased risk for cardiometabolic diseases. The gut microbiota also plays a role in the development of cardiometabolic dysfunction and is also subject to changes associated with age-related hormone changes. Phytoestrogens are plant-based estrogen mimics that have gained popularity as dietary supplements for treatment or prevention of menopause-related symptoms. These compounds have the potential to both modulate and to be metabolized by the gut microbiota. Hops (Humulus lupulus L.) contain potent phytoestrogen precursors, which rely on microbial biotransformation in the gut to estrogenic forms. We supplemented ovariectomized (OVX) or sham-operated (SHAM) C57BL/6 mice, with oral estradiol (E2), a flavonoid-rich extract from hops, or a placebo carrier oil to observe effects on adiposity, inflammation, and gut bacteria composition. Hops extract and E2 protected against increased visceral adiposity and liver triglyceride accumulation in OVX animals. Surprisingly, we found no evidence of OVX having a significant impact on the overall gut bacterial community structure. We did find differences in abundance of Akkermansia muciniphila, which was lower with HE treatment relative to the OVX E2 treatment and to placebo in the SHAM group.

New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

Incidental findings (IFs) depicted in imaging tests during diagnostic evaluation of patients with cleft lip and/or palate (CL/P) can guide clinicians during treatment-planning procedures for effective, comprehensive cleft care. Evidence regarding IFs in different anatomical regions distant from the dentition are scarce. The aim of this study was to compare the prevalence of IFs in various anatomical areas between patients with non-syndromic CL/P and unaffected subjects. Orthopantomographs (OPT), lateral cephalometric (LC) radiographs and cone-beam computed tomography (CBCT) scans of 120 subjects (case group: n = 40, 18 females, age 14.5 ± 5.0 years; control group: n = 80, 36 females, age 14.6 ± 4.9 years) were examined and IFs were assessed by four observers. Significantly higher prevalence of IFs (p &lt; 0.001) was reported in the case group (97.5%) compared with the control group (62.5%). The most prevalent location of IFs in the case group was the maxilla (92.5%), followed by the nasal cavity (75.8%) and the mandible (63.2%), while in the control group, the highest rates of IFs occurred in the maxilla (43.8%), mandible (41.3%) and temporomandibular joint (TMJ) (14.7%). No gender-dependent pattern for IF occurrence was detected overall. Orofacial clefts may affect the mandible. However, the reported IFs were limited compared to those in the maxilla. In conclusion, individuals with CL/P are more likely to present with a range of IFs than their unaffected peers. Understanding the association between CL/P and IFs is critical for successful interdisciplinary treatment, raising awareness of the potential need for future dental care for cleft patients, and managing extra-dental aberrations. A systematic assessment of diagnostic records is required to eliminate the risk of overlooking clinically significant IFs.

In the article, the results of research on a NiTi alloy with a high nickel content (51.7 at.%), produced using the additive technology SLM method and subjected to isothermal aging after so-lution annealing, are presented. The study involved the determination of the sequence of phase transformations occurring using differential scanning calorimetry (DSC), and the determination of the temperature range of these transformations. In parallel, the phase composition was determined using the XRD method; hardness and the Young’s modulus were also determined. The analysis of the DSC results obtained indicates the following characteristic features of the NiTi alloy, which change with ageing time: (1) during cooling (from +1500C to -500C), the type of transformation changes from a one-step transformation after solution annealing to a two-step transformation after the ageing process over 1, 20 and 100 hours at 500°C; (2) during heating (from -500C to +1500C) for all the samples, regardless of the ageing time, only a one-step transformation from martensite M(B19’) to austenite A(B2) is observed; (3) the temperature at which the transformation starts increases with the ageing time, (4) the width of the total temperature range of the transformation M(B19’)  A(B2) during heating changes from large (∆T=49,7°C), after solution annealing, to narrow (∆T=19.3°C and ∆T=17.9°C after 20 h and 100 h of ageing) and, most importantly, (5) a comparison with literature data shows that, irrespective of the composition of the NiTi alloy and the manufacturing technology of the alloy samples (regardless of the fact whether this was traditional or additive technology), a sufficiently long ageing process period leads to the occurrence of the martensite  austenite transformation in the same temperature range.

Quantitative dynamic strain measurements of the ground would be useful for engineering scale problems such as monitoring for natural hazards, soil-structure interaction studies and non-invasive site investigation using full waveform inversion (FWI). Distributed Acoustic Sensing (DAS), a promising technology for these purposes, needs to be better understood in terms of its directional sensitivity, spatial position, and amplitude for application to engineering-scale problems. This study investigates whether the physical measurements made using DAS are consistent with the theoretical reception patterns and experimental measurements of ground strain made by geophones. Results show that DAS and geophone measurements are consistent in both phase and amplitude for broadband (10s of Hz), high amplitude (10s of microstrain) and complex wavefields originating from different positions around the array when: (1) the DAS channels and geophone locations are properly aligned, (2) the DAS cable provides good deformation coupling to the internal optical fiber, (3) the cable is coupled to the ground through direct burial and compaction, and (4) laser phase noise is mitigated in the DAS measurements. The theoretical relationship between DAS-measured and point-wise strain for vertical and horizontal active sources is introduced using 3D elastic finite-difference simulations. The implications of using DAS strain measurements are discussed including directionality and magnitude differences between the actual and DAS-measured strain fields. A method for spatially aligning the DAS channels with the geophone locations at tolerances less than the spatial resolution of the DAS system is proposed.

Coffee has become a significant commodity for the people of Indonesia, including in Bener Meriah Regency. However, the quality of coffee remains low, partly due to deficiencies in the post-harvest process. This study aimed to analyze coffee farmers' post-harvest process in the Permata Sub-district and identify strategies to enhance coffee quality through farmers' institutions. The research method was qualitative, with data collection techniques comprising in-depth interviews and observation. The findings indicated that most coffee farmers in the Permata Sub-district lacked comprehensive post-harvest processing, impacting the coffee quality. The recommendations of this study emphasize the importance of strengthening coffee farmers' institutions, such as coffee farmer groups, to improve farmers' knowledge and skills in conducting optimal post-harvest processing following specialty coffee standards.

Introduction Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy, with a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multi-vessel coronary artery disease. Methods 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone, and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT group (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698) Conclusion Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes Acknowledgment funding „This work was supported by the University of Medicine, Pharmacy, Science and Technology ,, George Emil Palade’’ of Targu Mures Research Grant number 510/14/17.01.2022”

The focus of our study was the changes in the composition of semi-natural dry grasslands in Hungary. Since these valuable habitats were created with the help of humans, their preservation also requires regular treatment. Our mowing experiment aimed to investigate the suppression of the native Calamagrostis epigejos L. Roth. In Hungary, in the Cserhát Mountains, eight permanent plots were mowed twice a year. The vegetation was sampled annually between 2001 and 2011. The effects of mowing were investigated with repeated measures analysis of variance (ANOVA). After 10 years, the C. epigejos cover of the mowed plots decreased significantly, from the initial average of 62.38 to 7.50%. Surprisingly, we also experienced a similar decrease in the control plots. Regular treatment also had a positive effect on the number of species and diversity. Species richness increased continuously in both treatment types, which indicates the combined effect of vegetation succession and treatment. The biomass growth of other Poaceae and Fabaceae species, which are important from a grassland management perspective, was also facilitated by mowing. Our results suggest that long-term in situ experiments and continuous botanical studies are needed to establish a reliable utilization of grasslands.