Cytokines are a family of proteins which play a major role in the regulation of immune system, and enter the development of several diseases from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being spent in therapy and diagnosis, producing inhibitory drugs, as well as biosensors for a rapid, poor invasive, and effective detection. In this regards, even more efficient cytokine receptors are under investigation. In this paper we analyze a set of receptors of cytokine IL-6, investigating their topological features by means of a theoretical approach. Our results suggest a topological indicator that may help in the identification of those receptors having the highest complementarity with the protein, a feature expected to ensure a stable binding. Furthermore, we propose and discuss the use of these receptors in an ideal experiment.

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

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

One of the rare diseases throughout the world is Glycogen Storage Disease, which appears due to problems in glycogen metabolism. Among various subtypes of GSD, GSD Type 1a is the most abundant one of GSD Type 1, seen in approximately 80% and caused by different kinds of mutations in the Glucose-6-Phosphatase Catalytic Subunit (G6PC) gene in human chromosome 17q21. G6PC gene encodes for glucose-6-phosphatase (G6Pase) protein, which cleaves glucose-6-phosphate into glucose and inorganic phosphate (Pi), and GSD Type 1a patients fail to breakdown glucose-6-phosphate due to several mutations in the G6PC gene. In our study, we aim to create new therapeutic approaches for GSD 1a. We collected mutation data of 57 GSD Type 1a patients from Turkey. According to the data, 16 types of mutations were observed in the G6PC gene. Allele frequencies of these mutations are calculated as 59% for R83C/H, 11% for W160*, 7% for G270V, and 28% for others which have less frequency. Up to now, the tertiary protein structure of G6Pase has not been structured yet. To understand the possible impacts of these mutations, we statistically obtained possible tertiary structure predictions of G6Pase by running 5 different tools. At the end of the study, we suggest two effective and promising gene therapy methods for GSD Type 1a, Prime Editing for R83C/H mutations, and mRNA delivery for other mutations, in addition to a promising, commercially available drug suggestion for patients with W160*, W86*, and S15* mutations, although the drug belongs to another disease.

Shear dynamics simulation under extreme pressure was used to optimise the composition of ester-based lubricant base oil and extreme pressure additives. As a result, the ester-based lubricant in the weak-gel drilling fluid achieves reduction and increases the efficiency in drilling construction, and the field operation efficiency improves. The results of base oil lubrication simulation show that three base oils, namely, methyl oleate, ethyl oleate and butyl oleate, can be stably adsorbed on the surface layer of the shear surface. Methyl oleate has the lowest system temperature after shear stabilisation and has a high load-bearing capacity. The shear stress of methyl oleate decreases by changing the initial shear temperature and speed. It increases by 6.36 MPa when the speed increases from 10 m/s to 30 m/s. At this time, the shear stress of butyl oleate increases by 10.11 MPa. The results of the four-ball friction experiments show that the radius of the abrasion spot of methyl oleate is 179.83 μm, which is smaller than that of the other two base oils. Moreover, the friction coefficient of methyl oleate is 0.0018, which is approximately 1/3 of that of butyl oleate. Methyl oleate has better lubrication efficiency. The shear simulation results are consistent with the experimental results. The simulation can be used for the molecular design of lubricant materials. The oleic acid amide–containing amine group and the glyceride oleic–containing hydroxyl group were selected as the extreme pressure functional components for shear simulation. Results show that the shear stress of oleic acid amide is much lower than that of oleic acid glyceride when the initial shear temperature and speed change. The extreme pressure lubrication component–containing amine group is better than the extreme pressure lubrication material–containing hydroxyl group. The effects of different oleamide contents in the two-component mixtures on the lubricating properties were investigated through shear simulation, with methyl oleate as the base oil and oleamide as the extreme pressure functional component. The simulation results show that the lubricant has the optimal shear stress when 10% oleamide is added to the lubricant. The base properties of the lubricant were tested using a mixture of 90% methyl oleate and 10% oleamide, formulated as a lubricant. Results show that the friction coefficient can be reduced to 0.03 when 0.5% of the lubricant is added to the base mud. Moreover, the lubricant film formed shows high strength. Then, 1% lubricant was added to the weak-gel drilling fluid to evaluate the effect of the lubricant on the gel structure of the drilling fluid. Results show that adding lubricant does not affect the rheological properties of the drilling fluid. The gel structure of the system also remains stable even after 7 days of continuous ageing. The results of the field experiments in Hua3-01 well show that adding 1% ester-based lubricant to the field drilling fluid reduces the drilling friction by 33%. Thus, the efficiency of directional side drilling can be effectively improved, complicated accidents, such as poor starting and stopping of drilling and stuck jamming, can be avoided, and the goals of reducing quantity and increasing efficiency can be completed.

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

Series of bifunctional catalysts, MoS2/Al2O3(70 wt.%)-zeolite (30 wt.%) (zeolite – ZSM-5, ZSM-12, ZSM-22 and silica aluminophosphate SAPO-11), were synthesized for hydroconversion of methyl palmitate (10 wt.% in dodecane) in a trickle-bed reactor. Mo loading was about 7 wt.%. Catalyst and supports were characterized by different physical-chemical methods (HRTEM-EDX, SEM-EDX, XRD, N2 physisorption, FTIR spectroscopy). Hydroprocessing was performed at temperature of 250-350°C, hydrogen pressure 3.0-5.0 MPa, liquid hourly space velocity (LHSV) 36 h-1, H2/feed ratio – 600 Nm3/m3. Complete conversion of oxygen-containing compounds was achieved at temperature 310°C in the presence of MoS2/Al2O3-zeolite catalysts, the selectivity for the conversion of methyl palmitate via the ‘direct’ hydrodeoxygenation (HDO) route was over 85%. The yield of iso-alkanes gradually increases in order: MoS2/Al2O3 < MoS2/Al2O3-ZSM-12 < MoS2/Al2O3-ZSM-5 < MoS2/Al2O3-SAPO-11 < MoS2/Al2O3-ZSM-22. The sample MoS2/Al2O3-ZSM-22 demonstrated the highest yield of iso-alkanes (40%). Hydroisomerization activity of the catalysts was in a good correlation with concentration of Brønsted acid sites of synthesized supports.

The effects of methyl jasmonate (MeJ) on growth and taxoid formation in the cell culture of Himalayan yew was investigated for elucidate the specifics of the action of phytohormones on dedifferentiated plant cells in vitro. The characteristics of the same suspension culture of Taxus wallichiana was compared in 2017 ("young culture") and in 2022 ("old culture") - 1.5 or 6 years after culture induction, respectively. Cells were grown in flasks and bioreactors, MeJ (100 µM) was added at the exponential growth phase. It was found that cell culture demonstrated good growth (dry weight (DW) accumulation 10–18 g/l, specific growth rate µ = 0.15–0.35 day-1) regardless of "age", cultivation system and MeJ addition. UPLC–ESI-MS analysis showed the presence of C14-hydroxylated taxoids (yunnanxane, taxuyunnanine C, sinenxane C, sinenxane B) in cell biomass in the amounts comparable to plants. The content of C14-OH taxoids during 5 years of cultivation increased by 3-5 times. It was 0.2–1.6 mg/g DW for "young culture” and 0.6-10.1 mg/g for “old culture” depending on cultivation conditions. The ratio of individual compounds changed also: in the "young culture" was predominant yunnanxane, in the "old culture" - sinenxane C. Important that C13-hydroxylated taxoids were found in trace amounts only in the "young culture” (below 0.05 mg/g DW) and were not detected in the "old culture”. The response to MeJ was radically different depending on culture’s «age». In the “young culture”, exogenous MeJ had no effect on the content of C14-OH com-pounds, but significantly (almost 10 times) increased the content of C13-OH compounds. In particular, paclitaxel concentration was elevated up to 0.12–0.19 mg/g DW, which is comparable to its content in the bark of yew trees. By contrast, MeJ added to the "old culture” had minor effect on the synthesis of C13-OH toxoids that appeared in trace amounts only (below 3.5 µg/g DW for paclitaxel) but notably increased the content of C14-OH compounds (1.5–2.0 times in flasks and 5–8 times in bioreactors). These findings suggest that hormonal signaling in dedifferentiated yew cells grown in vitro is different from that in plants and change with culture age. This might be a result of the high level of heterogeneity of cells in vitro and their constant auto-selection for proliferate intensity which leads to predominant formation of C14-OH taxoids versus C13-OH taxoids and modified cell response to exogenous MeJ treatment. These results have both fundamental and practical biotechnological application.

Abstract: Agarose is known to form a homogeneous thermoreversible gel in aqueous medium over a critical polymer concentration. The solid-liquid phase transitions are thermoreversible but depend on the molecular structure of the agarose sample tested. Then, in a first step, the structure was characterised by 1H and 13C NMR in D2O and in DMSO which is a solvent of agarose whatever the temperature. A low yield in methyl substituent on the D-galactose unit was determined. Then, evolution of the 1H NMR spectrum was followed as a function of temperature in increasing and decreasing temperature process from 25 to 80°C. A large thermal hysteresis is obtained and discussed. It helps to interpret rheological behaviour. In fact, NMR signals are related to proton relaxation and especially to proton involved in H-bonds between water and -OH agarose for tightly bound water and agarose/agarose in chain packing. In a second step, water was exchanged against ethanol which is a non solvent of agarose. A stable gel was demonstrated and characterised by rheology to be compared with aqueous behaviour. Bound water playing the role of plasticizer is probably removed and the gel is much stronger (and brittle) in ethanol with a larger thermal stability. It is the first time that such gel is characterised without phase transition when passing from a good-solvent to a non-solvent. This extends the domains of application of agarose.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies were carried out, glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine, core- and/or an-tennary fucosylation. In the higher mass region these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as to understand pathogens molecular recognition.

Protein oligomerzation is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads abnormal protein oligomerization resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson’s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants: H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near physiological conditions. All three variants are found to adopt well folded and highly rigid structures in solution, although the elements of secondary structure are somewhat shorter than those observed in cystallography studies. R121C alters the environment of nearby residues only. By constrast, the mutation H13A affects local residues as well as nearby active site residues residues K41 and H119. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of most duplex structure and little or no G-quadruplex formation.

The research paper presents a new approach towards constructing motion equations for structures with attached MTMDs (multiple tuned mass dampers). A primary system, with MDOF (multiple dynamic degrees of freedom) was reduced to an equivalent system with a SDOF (single degree of freedom) through the modal approach, and equations from additional MTMDs were added to a thus-created system. Optimization based on H2 and H∞ for the transfer function associated with the generalized displacement of an SDOF system. The research work utilized GA (genetic algorithms) and SA (simulated annealing method) optimization algorithms to determine the stiffness and damping parameters for individual TMDs. The effect of damping and stiffness (MTMD tuning) distribution depending on the number of TMDs was also analyzed. The paper also reviews the impact of primary system mass change on the efficiency of optimized MTMDs, as well as confirms the results of other authors involving greater MTMD effectiveness relative to a single TMD.

The sound field properties for non-cavitating marine propellers are studied using FW-H (Ffowcs William-Hawkings) acoustic analogy and BEM (Boundary Element Method) approach. For the first time, the FW-H formula to calculate acoustic pressure generated by the propeller wake sheet is proposed. The corresponding sound signal can be dominant up to several kilometres. Secondly, non-physical fictitious volume flux is observed when the permeable FW-H approach is used together with BEM. The reason is explained and a virtual source correction method is proposed to solve this problem. Furthermore, analytical analyse show that the second thickness term and the first two loading terms in Farassat 1A formula are important, and the others are negligible. The numerical studies show that the permeable FW-H approach produces underestimation when compared to the direct FW-H method, and the underestimation is severer for larger permeable surface and higher frequency. It is also found that the first loading term in Farassat 1A formula is the dominant source term in the direct FW-H method, while the first thickness term is dominant when the permeable FW-H approach is used.

Cotton is one of the most important economic crops in the world, whereas insect attacks is a prime cause of its losses on yield and quality. Despite it is important, little is known about the mechanism of cotton response to insect. In this study, we simulated insect feeding by applying insect oral secretions (OS) to wounds, and combined transcriptome and metabolome analysis to comprehensively investigate how OS from two major pest species (Helicoverpa armigera and Spodoptera litura) affect cotton defense responses. Obvious differences were observed that 12,668 and 13,379 genes differently expressed respectively in cotton after being treated with different OS when compared with wounding along. Upon the addition of OS, JA-signaling pathway were rapidly and strongly induced, however SA-biosynthesis related gens were significantly down-regulated. By constructing the co-expression gene network, we identified a hub gene which encoding a leucine-rich repeat receptor kinase may play important role in recognition and signal transduction at early stage. We also found that OS from different insect species altered abundance of flavonoid related compound with different patterns. Interestingly, Gossypol which is a well-known anti-insect compound was kept a relative low content after OS application relative to wounding which implied the existence of the suppression effects of OS to cotton defense response. This study illustrated the transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species, identified potential key gene during the interaction process and finds the evidence for OS’s inhibition effects on cotton defense response.

The Koka gold deposit is located in the Elababu shear zone between the Nakfa terrane and the Adobha Abiy terrane, NW Eritrea. Based on the paragenetic study two main stages of gold mineralization were identified in the Koka gold deposit: 1) an early stage of pyrite-chalcopyrite-sphalerite-galena-gold-quartz vein; and 2) a second stage of pyrite-quartz veins. NaCl-aqueous inclusions, CO2-rich inclusions, and three-phase CO₂-H₂O inclusions occur in the quartz veins at Koka. The ore-bearing quartz veins formed at 268℃, from NaCl-CO₂-H₂O(-CH₄) fluids averaging 5 wt% NaCl eq. The ore-forming mechanisms include fluid immiscibility during stage I, and mixing with meteoric water during stage II. Oxygen, hydrogen and carbon isotopes suggest that the ore-forming fluids originated as mixtures of metamorphic water, meteoric water and magmatic water, whereas sulfur isotope suggest an igneous origin. Features of geology and ore-forming fluid at Koka deposit are similar to those of orogenic gold deposits, suggesting the Koka deposit might be an orogenic gold deposit related to granite.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

The number of citations that a paper has received is the most commonly used indicator to measure the quality of research. Researchers, journals, and universities want to receive more citations for their scholarly publications to increase their h-index, impact factor, and ranking respectively. In this paper, we tried to analyses the effect of the number of available Google Scholar versions of a paper on citations count. We analyzed 10,162 papers which are published in Scopus database in year 2010 by Malaysian top five universities. Then we developed a software to collect the number of citations and versions of each paper from Google Scholar automatically. The result of spearman correlation coefficient revealed that there is positive significant association between the number of Google Scholar versions of a paper and the number of times a paper has been cited.

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.

OBJECTIVE: To investigate the value of serum inflammatory factor levels in acute ischemic stroke patients after revascularization therapy in assessing acute prognosis. METHODS: 94 patients with acute ischemic stroke who underwent revascularization therapy admitted to our hospital from January 01, 2022 to January 01, 2024 were studied. The main evaluation index was modified Rankin Scale score (mRS) after 3 months, and patients with mRS score >2 were categorized into the poor prognosis group, and the rest were the good prognosis group. As well as the treatment of revascularization in all patients was used as a division into a thrombus extraction group and an intravenous thrombolysis group. Logistic regression analysis was applied to explore the independent risk factors for the prognosis of patients treated with recanalization for acute ischemic stroke. RESULTS: Two groups with good (59 cases) and poor (35 cases) prognosis were divided according to the mRS score. There were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The NIHSS score, hospitalization days, previous cardiac history, hospitalization days, LDL, fasting glucose, IL-6, and TNF-a at the time of admission were lower than those in the poor prognosis group, and the difference was statistically significant. In the patients in the embolization group, there were some differences in age, gender, emergency GLU, INR, whether they had diabetes or hypertension and other contents between the two groups, but the differences were not statistically significant. The pre-hospital NHISS score, IL-6, and TNF-a of patients in the good prognosis group were lower than those in the poor prognosis group, and the difference was statistically significant. CONCLUSION: IL-6 and TNF-α may be used as predictors of prognosis after revascularization therapy for acute ischemic stroke, and this conclusion also applies to patients in the embolization group.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Background: Skin is exposed to ultraviolet radiation (UV) and air pollution and recent works demonstrated these factors have additive effects in the disturbance of skin homeostasis. Nuclear factor erythroid 2-related factor 2 (Nrf2) and aryl hydrocarbon receptor (AHR) appears appropriate targets in the management of combined environmental stressors. The protective effects of Silymarin (SM), an antioxidant and anti-inflammatory complex of flavonoids, were evaluated. Methods: Reactive oxygen species (ROS) and interleukin 1-alpha (IL-1a) were quantified in UV+urban dust stressed reconstructed human epidermis (RHE) treated with SM. Gene expression study was conducted on targets related to AHR and Nrf2. SM agonistic activity on cannabinoid receptor type 2 (CB2R) was evaluated on mast cells. Clinical study quantified the performance of SM and cannabidiol (CBD), in skin exposed to solar radiation and air pollution. Results: SM decreased morphological alterations, ROS and IL-1a in UV+urban dust stressed RHE. AHR and Nrf2 related genes were upregulated that control antioxidant effector and barrier function. Interleukin 8 gene expression was decreased. Clinical study confirmed SM to improve homogeneity and perceived well-being of urban skins exposed to UV, outperforming CBD. SM activated CB2R and release of β-endorphin from mast cells. Conclusions: SM provides protection of skin from oxidative stress and inflammation caused by two major factors of exposome and appears mediated by AHR-Nrf2. SM activation of CB2R opens a new understanding of SM anti-inflammatory properties.

Objective: To evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. Results: 243 patients were included, ninety-five (44.2%) used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients treated with denosumab without CDK4/6 inhibitors the incidence of MRONJ and mean time to the occurrence of MRONJ was 6.6% (8/120) and 16.8 months (SD 7.8) respectively. In patients treated with denosumab and CDK4/6 inhibitor 13.7% (13/95) and 15.4 month (SD 8.7) respectively. The difference in the incidence was not significant (p=0.085). Conclusion: it suggest that the incidence of MRONJ in patients with metastatic breast cancer treated with denosumab was higher and the onset of MRONJ occurred earlier in the presence of CDK4/6 inhibitors. Although the difference was not significant, given that the use of this combination is very common in routine clinical practice, it would be advisable to carry out larger prospective studies to clarify the risk of this association.

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

Nanoporous films of Eu-doped organosilicate glass (OSG) have been synthesized using sol-gel technology and spin-coating, employing evaporation-induced self-assembly (EISA), on silicon wafers. The Eu doping is achieved by dissolution of Eu(NO3)3·6H2O in the precursor solution. The deposited films are characterized by using Fourier transform infrared (FTIR) spectroscopy, ellipsometric porosimetry (EP), X-ray photoelectron spectroscopy (XPS) and photoluminescence spectroscopy. It is observed that Eu doping makes the films more hydrophilic and reduces the pore size and open porosity. The reduction Eu3+ → Eu2+ occurs in the pores of OSG films, which is confirmed by depth profiling XPS. However, Eu3+ still presents on the film’s top surface. Presence of Eu3+ and Eu2+ gives characteristic luminescence emission in the range of 600‒630 nm (Eu3+) and 290‒400 nm (Eu2+). The Eu2+/Eu3+ concentrations ratio depends on CH3 groups concentration in the films. Moreover, concentration of Eu2+ ions in the pores can be reduced by exposure in inductively coupled (ICP) oxygen plasma. The observed shift of the luminescence spectra towards the UV region, in comparison to previously reported Eu-doped organosilicate films, can be attributed to the energy transfer occurring between the host material and Eu2+ ions.

Triglycerides of waste cooking oil reacted with methanol in refluxing toluene to yield mixtures of diglycerides, monoglycerides and fatty acid methyl esters (FAMEs) in the presence of 20% (w/w) catalyst/oil using the hydrophilic sulfonated silica (SiO₂-SO₃H) catalyst alone or with the addition of 10% (w/w) co-catalyst/oil [(Bun4N)](BF₄) or Aliquat 336]. The addition of the ammonium salts to the catalyst lead to a decrease in the amounts of diglycerides in the products, but the concentrations of monoglycerides increased. Mixtures of [(Bun4N)](BF4)/catalyst were superior to catalyst alone or Aliquat 336/catalyst for promoting the production of mixtures with high concentrations of FAMEs. The same experiments were repeated using DMSO as the solvent. The use of the more polar solvent resulted in excellent conversion of the triglycerides to FAME esters with all three-catalyst media. A simplified mechanism is presented to account for the experimental results.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

It has been discovered that representing odd integers as modified binary expressions ending with $2^m - 1$ for $m \geq 1$ helps in understanding the dynamics of Collatz-type sequences. Starting with the original Collatz sequence $3n + 1$, it is found that when the odd step is applied to an odd integer ending with $2^m - 1$, an even integer that ends in $2^{m+1} + 2^m - 2$ is obtained, which is exactly once divisible by 2, unless the lowest index reduces to zero. This implies that the sequence alternates between odd and even steps $m$ times. This governs the dynamics of the Collatz-type sequences because the value of $m$ determines the number of times the integer can be divided by 2 in each even step. A shortcut method is then presented that gives the even integer after $m$ odd-even steps are completed. This formulation also allows construction of odd integers to follow specific patterns of odd and even steps. The shortcut method for the modified Collatz sequence $5n+1$ is also presented.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

The stability issues in the widely known organic inorganic halide perovskite, CH₃NH₃PbI_3, lead to the development of alternative halide double perovskite materials which get great attention in recent times. Although the stability issue seems promising, both materials and device performance of these photovoltaic materials remain inferior and challenging for improvements. Furthermore, the power conversion efficiency of single junction organic inorganic halide perovskite is now 24.2% and 29.15% for textured monolithic perovskite/silicon tandem solar cell, but for all-inorganic halide perovskite solar cell is 7.11% and halide double perovskite solar cells based on Cs₂AgBiBr₆ and Cs₂TiBr₆ is 2.8% and 3.3%, respectively, which is far less than 24.2% and 29.15%, respectively. This creates big question and concern that can both all-inorganic halide perovskite solar cell and halide double perovskites solar cells really be an acceptable alternatives to replace organic inorganic halide perovskite solar cells or lead based perovskite solar cells in the market in order to realize the sustainable practical applications? Not only this concern, but also there are many other big challenges facing by halide double perovskite solar cells. Such big challenges include: a) geometric constraints and limited integration with interfacial materials, b) dynamic disorder and a wide band gap and localized conduction band caused by cubic unit cell which restrains the interactions of orbitals, c) high processing temperature which may limit on the diverse applications, d) low electronic dimensionality making them less appropriate for single junction solar cell purpose and etc. Moreover, origin of electronic and optical properties such as the polarizability, the presence of molecular dipoles and their influence on the dynamics of the photo-excitations in the halide double perovskites remains unlock concern that need to be elucidated. Now, another big question is how to develop overcoming mechanisms for such challenges. Can we really overcome these current limitations faced by halide double perovskites so that we use them for sustainable commercialization? This research roadmap for performance improvement is suggested focusing on: materials surface and bulk engineering, band gap engineering, interfacial engineering, composition engineering, doping engineering, device architectural engineering, polar and domain order engineering. This was the reason that this review was developed in order to forward great contributions to the readers and commercial ventures.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Nitrogen oxides (NOx), pivotal atmospheric pollutants, significantly imperil the environment and human health. The CH4-SCR process, leveraging the abundant and accessible methane (CH4), emerges as a promising avenue for NOx abatement. Previous studies have demonstrated that zeolite support with twelve-membered ring (12-MR) and five-membered ring (5-MR) structures are susceptible to framework collapse in the presence of water, leading to catalyst deactivation. Consequently, there is a necessity to explore novel zeolites with enhanced hydrothermal stability for application in CH4-SCR processes. This research introduced for the first time an investigation into a novel In-H-SSZ-39 catalyst, synthesized via ion exchange and meticulously optimized for preparation conditions, including calcination temperature, In ions concentraiton, and reaction conditions, including CH4/NO ratio, O2 concentration, water vapor content, and Gas hourly space velocity (GHSV). Notably, the In/H-SSZ-39 catalyst achieved superior performance of 42.1% at 605 °C, with a calcination temperature of 500 °C and an In ion concentration of 0.066 M, under CH4/NO ratio of 1.5:1, 10% O2, and GHSV of 21000 h-1. In addition, the catalytic performance was influenced by the concentration of water vapor and the GHSV value.

On the H-type group G⊂Rm×Rn, we study the existence of solutions for the Brezis-Nirenberg problem

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

Nanoindentation load-depth (P-h) plots is the basis for determination of mechanical properties of the samples and is especially vital for thin coatings deposited on substrates of various mechanical makeup from amorphous-brittle (borosilicate glass) to Silicon (having different crystallographic texture) to ductile substrates like stainless steel as well other aspects like indenter tip shape. The elastic-plastic response by simulated P-h plots as per modified empirical relations have been presented. The outcomes of this computational studies enlighten the database on the P-h plots for various coating/substrate systems and shall aid in the analysis of experimental P-h plots obtained,

Sumatriptan is a serotonin receptor agonist approved by FDA in 1992 to treat migraines. Its’ solid form used in commercially available drugs Imitrex, Treximet, Onzetra Xsail and Zembrace symtouch is sumatriptan succinate. Herein we report on crystal structure of sumatriptane succinate hemi(ethanol solvate), HSum+·HSucc–·0.5EtOH, its comparison with previously reported solids containing derivatives of sumatriptan.

This paper addresses a mode-dependent state-feedback H∞ control for descriptor hybrid systems, considering both the absence and presence of actuator saturation. Firstly, the necessary and sufficient conditions for the stochastic admissibility criterion with H∞ performance ? of the closed-loop system is proposed. Given the proposed non-convex condition, the author reformulates it into linear matrix inequalities (LMIs). Then, to extend the result to the systems with actuator saturation, the actuator saturated control input is expressed as a linear combination of given state-feedback control input and a virtual control input that remains under the saturation level. To verify this expression, the set invariant condition is also suggested by using the singular mode-dependent Lyapunov function candidate. Therefore, the LMI conditions for the existence of the mode-dependent state-feedback H∞ control and the ellipsoidal shape of invariant set are successfully derived. Two numerical examples demonstrate the effectiveness of the proposed approach in optimizing H∞ performance $\gamma$ and identifying the largest invariant set.

This paper presents various procedures for determining the optimal control law for a wing section in compressible flow. The flow regime includes subsonic as well as supersonic flows. For the evolution of the system in the Laplace plane the present method makes use of the exact unsteady aerodynamic forces in the Laplace plane once the control law is established. This is a great advantage against other results previously published, where the unsteady aerodynamics in the Laplace plane are just approximations of the curve-fitted values in the frequency domain (imaginary axis). Different control techniques are investigated like pole-placement, LQR and H-infinity norm. Among these, the H-infinity norm emerges as the optimal choice, exhibiting a norm magnitude approximately two orders of magnitude lower than the LQR case. Furthermore, the H-infinity controller demonstrates lower pole values that those of the pole placement and LQR compensator, showing the advantage of the H-infinity controller in terms of economic efficiency.

Using the colloidal method, Au NP’s were deposited onto 6 different supports (TiO2,  and -Al2O3, HFeO2, CeO2, and C), and their catalytic activity and selectivity were compared in the alkylation of aniline by benzyl alcohol. Correlations were made between the nature of the support, the Au NP size and H-binding energy.

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

The closed forms of the non-resonant thermonuclear function in the Maxwell-Boltzmann and Tsallis case with depleted tail are obtained in generalized special functions. The results are written in terms of H-function of two variables. The importance of the results in this paper lies in the fact that the reaction rate probability integrals in Maxwell-Boltzmann and Tsallis cases are not obtained by the conventional method of approximation or by means of a single variable transform technique but by means of a two variable transform method. The Behaviour of the depleted non-resonant thermonuclear functions are examined using graphs. The results in the paper are of much interest to astrophysicists and statisticians in their further work in this area.

This paper proposes a multifractal model, with the aim of providing a possible explanation for the locality phenomenon that appears in the estimation of the Hurst exponent in stationary second order temporal series representing self-similar traffic flows in current high-speed computer networks. It is shown analytically that this phenomenon occurs if the network flow consists of several components with different Hurst exponents.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

Red mud (RM) is a residue obtained from the production of alumina. It contains a high concentration of metal oxides and waste concentrated sodium hydroxide solution (pH = 13). To increase the value of RM, an environmentally friendly process of transesterification using waste cooking oil (WCO), MeOH and concentrated sodium hydroxide solution (CSHS) from aluminum production was proposed. Triglycerides of WCO reacted with MeOH at 60 oC to yield mixtures of fatty acid methyl esters (FAMEs) in the presence of 2.03% (w/w) CSHS/WCO using the CSHS (0.204 mol L-1, predetermined by potentiometric titration) from aluminum production by the Bayer process or with the addition of 0.68% (w/w) fabric softener (3% w/w cetyltrimethylammonium chloride in solution) as a phase transfer (PTA) agent. The addition of PTA to the catalyst resulted in a better yield of the products (greater than 98% yield). A simplified mechanism is presented to account for the experimental results.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Backround: Thoracic trauma causes life-threatening organ injuries, ranging from simple abrasions to contusions of intrathoracic organs. In this study, we aimed to investigate the effects of bosentan on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Methods: Thirty-seven animals male Sprague-Dawley rats were divided into 5 groups. All 4 groups, except for the control group, were performed to PC. In the first group, C: control group (n=6) consisted of unprocessed and untreated. The second group, PC3 (n=8) underwent of 3 days PC performed. The third group, PC-B3 (n=8) received 100 mg/kg bosentan was given orally once a day for 3 days. The fourth group, PC7 group (n=7) underwent of 7 days PC performed, and the fifth group PC-B7 (n=8) received 100 mg/kg bosentan was given orally once a day for 7 days. While ET-1, NF-B, TNF-, and HIF-1 was measured by ELISA method, TAC and PAB by spectrophotometric in lung tissue samples. Results: ET-1, NF-B, TNF-, HIF-1, and PAB levels were higher, while TAC activities were lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-- levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05) while NF-B, HIF-1, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan treatment causes decreased ET-1, NF-B, TNF-, HIF-1, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: We found that the use of bosentan decreased the severity of oxidative stress in the lung and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, oxidative stress in some diseases that may be accompanied by ischemia.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

In the dynamic landscape of modern education, characterized by an increasingly active involvement of IT technologies in learning, the imperative to transfer to students the skills necessary to integrate Artificial Intelligence (AI) into the process represents an important goal. This paper presents a novel framework for knowledge transfer, diverging from traditional programming language-centric approaches by integrating PSoC 6 microcontroller technology. This framework establishes a cyclical learning cycle encompassing theoretical fundamentals and practical experimentation, fostering AI literacy at the edge. Through a structured combination of theoretical instruction and hands-on experimentation, students develop proficiency in understanding and harnessing AI capabilities. Emphasizing critical thinking, problem-solving, and creativity, this approach equips students with the tools to navigate the complexities of real-world AI applications effectively. By leveraging PSoC 6 as an educational tool, a new generation of individuals is efficiently cultivated with essential AI skills. These individuals are adept at leveraging AI technologies to address societal challenges and drive innovation, thereby contributing to long-term sustainability initiatives. Specific strategies for experiential learning, curriculum recommendations, and results of knowledge application are presented, aimed at preparing students to excel in a future where AI will be omnipresent and indispensable.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Surfactants are amphiphilic molecules and one of the most versatile products of the chemical industry. They can be absorbed at the air-water interface and can align themselves so that the hydrophobic part is in the air while the hydrophilic part is in water. This alignment lowers the surface or interfacial tension. Gemini surfactants are a modern variety of surfactants with unique properties and a very wide range of potential applications. Hexamethylene-1,6-bis(N-dodecyl-N,N-dimethylammonium bromide) is one such representative compound that is a better alternative to a single analogue. It shows excellent surface, antimicrobial, and anticorrosion properties. With a highly efficient synthetic method and a good ecological profile, it is a potential candidate for numerous applications, including biomedical applications.

Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.

Helicosporous hyphomycetes is a class of filamentous fungi that shows promising application prospects in metabolizing bioactive natural compounds. During a study of helicosporous fungi in China, six new helicosporous taxa were collected and isolated from decaying wood in Guangxi Zhuang Autonomous Region, China. Morphological comparisons with multi-gene phylogenetic analyses revealed that these six taxa belong to Helicosporium (Tubeufiaceae, Tubeufiales), and they can be recognized as three novel species, named Helicosporium liuzhouense, H. multidentatum and H. nanningense. Detailed descriptions and illustrations of the newly discovered taxa and comparisons with similar fungi are provided. In addition, a list and a key to accepted Helicosporium species are provided.

This paper presents the values of several mechanical characteristics for two blends: H (60% PP + 12% PA6 + 8% EPDM + 20% Polybond 3200) and G (20% PP + 42% PA6 + 28% EPDM + 10% Polybond 3200) (%wt), comparing them to those of PP (polypropylene) and PA6 (polyamide 6). The adding of EPDM (ethylene propylene diene monomer rubber) and Polybond 3200 help reducing the disadvantages of simple blends made of PP+PA6, when the PA6 concentration allows for having a PA6 matrix with droplets of PP. SEM analysis helps for understanding the performance of material G as compared to the neat polymers. EDX analysis proved that there was a matrix inversion, material H having a PP matrix and material G a matrix made of PA6 with droplets of PP. Strain at break for PP and material H were proved to be insensitive to test speed, but materials G and PA6 had large value for strain at break and energy at break for v = 10 mm/min. Taking at basis the values for polyamide 6 (PA6), material G has greater values for energy at break: with 97.8% for v = 10 mm/min, with 29.5% for v= 250 mm/min and with 98% for 1000 mm/min, without exhibiting the micro and macro cavitation of PA6. This means that the recipe, the technology and the mechanical characteristics make material G a potential candidate for applications where a low and moderate impact resistant material is required.

Two 2,2':6',2''-terpyridine-based Schiff bases (TPySSB and TPySB) have been synthesized. The TPySSB shows remarkable selective ‘off-on’ fluorescence for Al³⁺ by photoinduced electron transfer (PET) mechanism of sensing. Chemosensor TPySSB binds Al³⁺ in a 1:2 ratio with an association constant 6.8×10⁵ (R²=0.98) and this 1:2 stoichiometric model is established on Job’s plot and ¹H NMR. Compared TPySSB and TPySB, it is of great importance of the existence of salicylidene unit due to its strong binding abilities of both phenol and C=N structure to the Al³⁺.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host–guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule which is captured by PCP6 via electrostatic interactions and π-π interactions. Therefore, a selective and sensitive fluorescence sensor for TNP detection is developed. It has a low detection limit of 0.0035 μM (S/N=3) and a wider linear response of 0.01−5.0 and 5.0−125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

In this work, nylon 6/ P(N-phenylmaleimide-alt-styrene) blends were prepared by melt blending, and the mechanical, heat-resistant, crystallographic and dynamical mechanical properties of nylon 6/ P(N-phenylmaleimide-alt-styrene) blends with different contents were investigated and analyzed. The results showed that the mechanical properties decreased with increasing PNS, while the heat deflection temperature (HDT), relative crystallinity (Xn), and storage modulus (G’) increased with increasing PNS. The results of differential Scanning Calorimetry (DSC) proved the PNS played the positive role of nucleating PA6. And the results of dynamic mechanical analysis (DMA) proved the PNS could improve the rigidity of PA6/PNS blends. From the SEM, these PNS domains were between 0.2 and 4 μm in diameter. The experimental results indicated that the addition of PNS improved the rigidity of PA6/PNS blends, and then improved the heat-resistant property.

According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Using the h-index to assess individual researchers is not only unethical and unfair but also inaccurate and misleading. This index fails to offer a reliable measure of a researcher's impact based on their citation scores. Beyond statistical and conceptual considerations, authorship practices, especially in the case of multi-authored publications, give rise to significant problems that often go unnoticed. While some modifications of the h-index have been proposed to mitigate these weaknesses, the fundamental deficiencies persist. Most of these flaws have been effectively addressed by the c-score, a composite citation index. The c-score excludes self-citations, normalizes the number of citations by considering the number of authors in each paper, and takes into account first, single, and last authorship. This approach provides a more realistic measure of the impact of each individual researcher based on raw citations.

Individuals with Parkinson’s disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MRL) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in freezers. Thirty-four freezers were assessed in the ON-medication state. During a functional magnetic resonance imaging protocol of simulated APA task, we assessed beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR), in addition to PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APAs amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2=0.32, P=0.0006) and APA amplitude (R2=0.13, P=0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Helicobacter pylori, a gram-negative bacteria usually found in stomach and first part of small intestine, is known to cause infections and ulcers and may have association with cancer. Normally, the treatment options include combinations of antibiotics with proton pump inhibitors and antiinflammatory drugs. However, all of them have high systemic exposure, and hence, unfavourable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is very limited. We have attempted to develop a predominantly gut-restricted formulations of antibiotic + adjuvant combinations as a basis for potentially more safe and efficacious treatment of gastrointestinal tract infections. We have considered E. coli (as a model of H. pylori) and Lactobacilli to study the antibacterial activity of nanogel with combined drugs (classical antibiotics and individual components of essential oils). It has been shown that levofloxacin (LF) in combination with zephirol demonstrates synergy effect against E. coli (cell viability has decreased by about 50%) and weakens the effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant is also shown to be effective. Using FTIR and UV spectroscopy, it has been proved that chitosan nanogels with the drug are well adsorbed on the mucosal model, thereby increasing the bioavailability of drugs. Using ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which is potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. Thus, chitosan nanogels loaded with a combination of drugs can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract, and applicable to difficult-to-treat bacteria.

The increased emergence of multidrug-resistant Helicobacter pylori influences the prevention of stomach cancer. Zingiber officinale is a plant usually used in folk medicine to treat a variety of diseases involving infections, nausea, vomiting, peptic ulcer, dyspepsia, and inflammation. This study was conducted to evaluate the ability of Z. officinale extract to combat resistant H. pylori. The disc diffusion, microdilution, and microplate assays were performed to evaluate the susceptibility to antibiotics, and the antibacterial and antibiofilm activities of the Z. officinale extracts. Using the checkerboard method, the combined effects of the gentamicin and Z. officinale extract were investigated. In addition, anti-inflammatory activity and GC-MS analysis were determined by the modified protocol. According to the findings, H. pylori isolates exhibited resistance rates of 56.33, 50.0, and 45.85 for metronidazole, gentamicin, and tetracycline, respectively. The methanolic extract of Z. officinale had the strongest effectiveness against resistant H. pylori isolates with MIC of 20.0 to 50.0 µg/ml against both H. pylori isolates and the stranded strain NCTC 11637. Z. officinale extract suppress the biofilm formed by H. pylori isolates with a percentage of 92.96% at 50.0µg/ml, compared with 97.19% for gentamicin at the same concentration. According to FICI values, combination of methanolic Z. officinale extract to gentamicin increases bacterial sensitivity to such drugs. Moreover, the Z. officinale extract exhibits strong anti-inflammatory activity. The GC-MS analysis of Z. officinale extract exhibits 17 different chemical compounds. Conclusions: The Z. officinale extract contain the anti-inflammatory compound gingerol as the main constituent which inhibits the growth of H. pylori and its biofilm, are a promising natural therapeutic alternative or enhance antibiotics activity

Lead, known as a metal with high neurotoxicity to children, cadmium, which is a carcinogenic and bioaccumulative contaminant, and arsenic, a class 1 carcinogenic according to the International Agency for Research on Cancer, are toxic elements (TEs) whose relevant route of exposure may be diet. We determined the bio-accessible fraction of lead, cadmium, and arsenic from the diet of preschool children from two day care centers (DCC). A cross-sectional study was conducted with 64 one–four-year-old children from two DCCs where the 24-h duplicate diet samples were collected. The diet samples were analyzed by ICP-MS for lead, cadmium, and arsenic total concentrations (n = 64) and their bio-accessibility were analyzed for a subsample (n = 10). The dietary intake (DI) mean for lead, cadmium, and arsenic were 0.18 ± 0.11 µg kg⁻¹ bw, 0.08 ± 0.04 µg kg⁻¹ bw, and 0.61 ± 0.41 µg kg⁻¹ bw, respectively. All DI calculated for TEs, considering total intake, were found lower than the tolerable limits (TL) (European Union, or World Health Organization, WHO, when applicable) except for one child’s Pb intake. Bio-accessibilities ranged between 0% to 93%, 0% to 103%, and 0% to 69%, for lead, cadmium, and arsenic, respectively. Although DI for TEs has been found lower than TL, these reference values have been recently decreased or withdrawn since it was for lead and arsenic whose TL were withdrawn by WHO.

It is argued that if the non-unitary measurement transition, as codified by Von Neumann, is a real physical process, then the ‘probability assumption’ needed to derive the Second Law of Thermodynamics naturally enters at that point. The existence of a real, indeterministic physical process underlying the measurement transition would therefore provide an ontological basis for Boltzmann’s Stosszahlansatz and thereby explain the unidirectional increase of entropy against a backdrop of otherwise time-reversible laws. It is noted that the Transactional Interpretation (TI) of quantum mechanics provides such a physical account of the non-unitary measurement transition, and TI is brought to bear in finding a physically complete, non-ad hoc grounding for the Second Law.

Iron-based materials are widely applied in Fenton chemistry and they have promising prospects in the processing of wastewater. The composition complexity and rich chemistry of iron and/or oxides, however, hamper the precise understanding on the active sites and the working mechanism which still remain highly controversial. Herein, iron oxides of four different model systems are designed through a conventional precipitation method plus H2 reduction treatment. These systems feature Fe@Fe3O4 with abundant oxygen vacancy, Fe0 and Fe3O4 particles with interface structures, and Fe3O4-dominated nanoparticles of different sizes. These materials are applied in the decomposition of methyl orange as a model reaction to assess the Fenton chemistry. The Fe@Fe3O4 with core-shell structures exhibited significantly higher decomposition activity than the other Fe3O4-rich nanoparticles. A thin Fe3O4 layer formed by auto-oxidation of iron particles when exposing to air can boost the activity as compared with the Fe0 and Fe3O4 particles with interface structures but poor oxygen vacancy. The unique hetero-structure with the co-existence of both metallic iron and oxygen vacancy displayed excellent redox propensity which might account for the superior Fenton activity. This finding provides a new perspective to understand and design highly efficient iron-based Fenton catalysts.

Red mud (RM) is composed of a waste alkaline solution (pH = 13.3) obtained from the production of alumina. It contains high concentrations of soluble hematite (Fe2O3), goetite (FeOOH), gibisite [Al(OH)3], a boemite (AlOOH), anatase (Tetragonal - TiO2), rutile (Ditetragonal dipyramidal - TiO2), hydrogarnets [Ca3Al2(SiO4)3−x(OH)4x], and perovskite (CaTiO3). It was shown to be an excellent catalytic mixture for biodiesel production. To demonstrate the value of RM, an environmentally friendly process of transesterification in aqueous medium using waste cooking oil (WCO), MeOH and waste alkaline solution (WAS) obtained from aluminum production was proposed. Triglycerides of WCO reacted with MeOH at 60 oC to yield mixtures of fatty acid methyl esters (FAMEs) in the presence of 0.019% (w/w) WAS/WCO using the WAS (0.204 mol L-1, predetermined by potentiometric titration) from aluminum production by the Bayer process. The use of the new catalyst (WAS) resulted in a high yield of the products (greater than 99% yield).

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

Ensuring access to water, sanitation, and hygiene (WASH) facilities, coupled with behavior change education in schools, is fundamental for fostering a conducive learning environment and promoting principles of inclusion, dignity, and equality. This study focuses on 12 primary schools in Anápolis, Brazil, encompassing 4,394 students and 248 teachers. WASH assessments were conducted through a questionnaire, observation of water and sanitation facilities and structures, and microbiological analysis. Over the period 2018 to 2020, the proportion of schools with safely managed drinking water surged from 42% to 92%. However, sanitation conditions in the schools were categorized as a basic level, with hygiene services rated as limited in 92% of the schools due to the absence of soap. While this study reveals that Anápolis schools generally align with WASH guidelines for basic/advanced drinking water services, there is a crucial need for enhancements in both hardware and software facilities to address sanitation and hygiene challenges.

Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO, in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers signed informed consent. Complete blood count, blood chemical tests, carcinoembryonic antigen (CEA) carcinoma antigen 125 (CA125), carcinoma an-tigen 19.9 (CA19.9), d-dimer, fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in complete pathological re-sponse (pCR) vs non-pCR group (3.71 pg/mL vs 7.63 pg/mL, p=0,004). In all patients with IL-6 levels below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs ypN0 (7.69 pg/mL vs 2.89 pg/mL, p=0.022). Conclusions: The trial showed that elevated level of IL-6 prior to treatment and C2 might be a predictor of pathologic response to NAC.

Metal complexes of mesoionic carbenes (MICs) of the triazolylidene-type and their derivatives have gained increasing attention in the fields of electrocatalysis and photochemistry. The redox-activity of these metal complexes is critical for their applications in both the aforementioned fields. Easy accessibility and modular synthesis open a wide field for the design of ligands, such as bidentate ligands. The combination of a MIC with a pyridyl unit in a bidentate ligand setup increases the π-acceptor properties of the ligands while retaining their strong σ-donor properties. The analogy with the well-established 2,2'-bipyridine ligand allows conclusions to be drawn about the influence of the mesoionic carbene (MIC) moiety in tetracarbonyl group 6 complexes in cyclic voltammetry and (spectro-)electrochemistry (SEC). However, the effects of the different connectivity in pyridyl-MIC ligands remains underexplored. Based on our previous studies, we present here a thorough investigation of the influence of the two different pyridyl-MIC constitutional isomers on the electrochemical and the UV-vis-NIR/IR/EPR spectroelectrochemical properties of group 6 carbonyl complexes. Moreover, the presented complexes were investigated for the electrochemical conversion of CO2 using two different working electrodes, providing a fundamental understanding of the influence of the electrode material in the precatalytic activation.

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria (6-hydroxy-L-nicotine) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those no later than July 2023, was conducted. The search focused specifically on articles pertaining to nicotine metabolites, memory, oxidative stress, cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 185 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6-hydroxy-L-nicotine.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of RT-PCR and qRT-PCR found that the relative expression of PLD6 gene in the testicular tissues of 2-year-old Simmental calves was significantly higher than that of 6-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker VASA. Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piRNA binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and PIWIL2. In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

Epidemiologic studies suggest an inverse correlation between coffee consumption and the occurrence of neurodegenerative diseases, but the role of caffeine and roasting degree are still matter of debate. The objective of this work was to evaluate the effects of caffeinated (light, medium, and dark roast) and decaffeinated instant coffee samples in acetylcholinesterase inhibition and antioxidant assays, as well as in animal models of Parkinson’s disease. Caffeinated coffees inhibited the acetylcholinesterase in much smaller concentrations than decaffeinated coffee. All coffee samples showed antioxidant capacity without relation with the caffeine content. Dopaminergic-like activity in the haloperidol-induced catalepsy test was observed with caffeinated coffee, but not in the decaffeinated sample. The medium roast coffee reduced the number of rotations of rats after methamphetamine administration on the 6-hydroxydopamine unilateral lesion of the medial forebrain bundle. However, the coffee treatment did not avoid the loss of dopaminergic neurons on substantia nigra pars compact and only the smallest dose of coffee was able to avoid the decrease of dopamine levels in the lesioned side of the striatum. Altogether, these results suggest that coffee exerts moderate pro-cholinergic and pro-dopaminergic effects and caffeine seems to be the main responsible for these effects.

The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.

Background: Cytokines are multifunctional glycoproteins playing a vital role in the tumor microenvironment and in the progression of breast cancer. The immune responses in the tumors restrained by pro- and anti-inflammatory cytokine expressions could be influenced by genetic polymorphisms. Hence, the present study evaluated the contribution of IL6 (rs1800797, rs1800796, and rs1800795), and IL18 (rs1946518, rs187238, and rs549908) genotypes and its haplotypes with risk and progression of breast cancer in south Indian population. Methods: The polymorphisms of IL6 gene -597G>A, -572G>C, -174G>C and IL18 gene -607C>A, -137G>C, and 105A>T were genotyped through PCR-RFLP and As-PCR assays in blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression and Kaplan-Meier analyses for the obtained data. Results: The frequency of AA genotype & A-allele of IL6 -597G>A, and CC genotype & C allele of IL6 -174G>C polymorphism was higher in breast cancer patients and was found to be significantly associated with TNM staging, late (advanced) stage, metastasis, etc. While, CG and GG genotypes of IL6 -572 C>G polymorphism had a protective role against breast cancer. Further, IL18 -607C>A, -137G>C & 105A>T polymorphisms were found to be associated with lobular carcinoma subtype, PR-ve and HER2+ve breast cancer patients. Perfect LD was observed between all SNPs of IL6 & IL18 genes under study; G-C-C, A-G-G and A-C-C haplotype combination of IL6 genes had conferred 2.09, 2.25 and 4.72 folds risk for breast cancer respectively. In survival analysis, we observed that the C allele of rs 1800795 was found to be significantly associated with 5years overall survival in breast cancer subjects. Conclusions: Overall, our results suggest the importance of genotypic and haplotype analysis of IL6, and IL18 gene variants in progression and risk identification of breast cancer.

Nonwovens made of recycled carbon fibers (rCF) and thermoplastic (TP) fibers have excellent economic and ecological potential. In contrast to new fibers, recycled carbon fibers are significantly cheaper and the CO2 footprint is mostly compensated by energy savings in the first product life cycle. The next step for this promising material is its industrial serial use. Therefore the process chain from fiber to composite material is analyzed. Initially rCF length at different positions during the carding process is measured. Thereafter the influence of the TP fibers onto processing, fiber shortening and mechanical properties is evaluated. At last several nonwovens with different TP fibers and fiber volume contents between 15 vol.-% and 30 vol.-% are produced, consolidated by hot pressing and tested by 4-point bending to determine the mechanical values. The fiber length reduction ranges from 20.6 % to 28.4 %. TP fibers cushion the rCF against mechanical stress but hold rCF fragments back due to their crimp. The resulting bending strength varies from 301 MPa to 405 MPa and the stiffness from 16.3 GPa to 30.1 GPa. Design recommendations for reduced fiber shortening are derived as well as material mixtures which offer better homogeneity and higher mechanical properties.

A series of Ni/KIT6 catalystprecusors with 25wt.%Ni loading amount were reduced in H₂ at 400, 450, 500, and 550ºC, respectively. The studied catalysts were investigated by XRD, Quasiin-situ XPS, BET, TEM, and H₂-TPDanalysis methods.It was found that reduction temperature is an important factor affecting the hydrodeoxygenation (HDO) performance of the studied catalysts. The reduction temperature influences mainly the content of active components, crystal size, and the abilityfor adsorbing and activatingH2. The developed pore structure and large specific surface area of the KIT-6 support favored the Ni dispersion.The RT450 catalyst, which was prepared in H₂ atmosphere at 450 ºC, has the best HDO performance. Ethyl acetate can be completely transformed, and maintain 96.8% ethane selectivity and 3.2% methane selectivity at 300 ºC. The calculated apparent activation energies of the prepared catalysts increased in the following order: RT550 > RT400 > RT500 > RT450.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, it is critical to provide genetic counseling to the patient's relatives in order to reduce the risk of transmitting WS1. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric diseases commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

This article is some review of results that were obtained at 2007-2021 years development of “The Information as Absolute” concept and the informational physical model, which is based on the concept; including a number of fundamental physical problems are briefly considered in framework of the conception and the model. Recently in physics there are several publications, that present lists of the problems. However, those lists are essentially incomplete, for at least two reasons. Firsts of all, a number of phenomena are studied traditionally by philosophy, and so corresponding problems are usually considered to be “metaphysical”. However, they relate also to some concrete physical phenomena. For example, physics evidently studies Matter, and so the metaphysical problems “what is ontology of Matter”, “what is “Space”, “Time” and a few other physical phenomena and notions as well, are really a Meta-physical problems “what does physics study?” There are other fundamental physical problems, which are not considered as such in physics, and are absent in the “fundamental problems lists”. Those include the problems, which really exist, yet are incorporated into standard physical theories, and so are fundamental “implicitly”, which in physics are “solved by default” ‒ and mostly erroneously. Note, though, that a number of “Meta-physical”, and concrete fundamental, problems more in detail are considered in the paper “The Informational Conception and Basic Physics”, https://arxiv.org/abs/0707.4657, v5 (2021), so this paper is, in certain sense, an expanded conclusion of this paper, which includes, correspondingly, more in detail consideration of some more general physical problems; and, besides, in this article, the problem “what are Gravity and Electric Forces” is essentially clarified comparing with the arXiv 2021 paper version above. Besides, the concrete problem “What is Life”, and the rational cosmological model, where a few vague points in standard cosmology rather probably are rationally clarified, while the fundamental problem “matter – antimatter asymmetry” in Matter is solved practically for sure, are considered, and one of recently published rather complete “lists of fundamental problems” is commented in Appendix.